Abstract:Objective：To investigate the mechanism by which TANK binding kinase 1（TBK1）regulates the activation of nucleotide-binding oligomerization domain -like receptor 4（NLRC4）inflammasome. Methods：Western blot was used to detect the activation of NLRC4 inflammasome and their downstream molecules cysteine aspartic acid-specific protease 1（Caspase-1）and Gasdermin D （GSDMD）in immortalized bone marrow-derived macrophages（IBMDM）infected with Salmonella typhimurium（S.T）. A lactate dehydrogenase detection kit was used to detect the content of lactate dehydrogenase in the supernatant of cell culture medium. The interaction between TBK1 and NLRC4 and their specific interaction domain was determined through protein co -immunoprecipitation experiments. Cellular immunofluorescence assay was used to determine the spatial localization of TBK1 and NLRC4. The GST pull-down experiment confirmed the direct interaction between TBK1 and NLRC4. The assembly of NLRC4 inflammasome was verified using apoptosis-associated speck-like protein containing a CARD（ASC）oligomerization detection experiments. The S.T infected animal model of C57BL/6 mice was built and the survival of mice was observed. The bacterial load of lung tissues and peritoneal cavity-flushed fluid was analyzed through smear analysis. ELISA was used to detect the content of tunor necrosis factor（TNF）- α and interleukin（IL）-1β in peritoneal cavity -flushed fluid and serum. Flow cytometry was used to detect the proportion of neutrophils in peritoneal cavity-flushed fluid. Results：In S.T infected IBMDM，inhibiting TBK1 led to a weakened activation of NLRC4 inflammasomes，decreased phosphorylation levels of NLRC4，and reduced cleavage of Caspase-1 and GSDMD. There was an interaction between TBK1 and NLRC4，and the N-terminal of TBK1 interaced with the NACHT domain of NLRC4. TBK1 and NLRC4 had spatial co-localization. TBK1 phosphorylated the NLRC4 Ser533 site. S.T animal model experiments showed that inhibiting TBK1 activity significantly improved the survival rate of mice，weakened the bacterial load in the peritoneal cavity -flushed fluid and lung tissues of mice，reduced the content of IL-1β and TNF-α in serum and peritoneal cavity-flushed fluid，and reduced the proportion of neutrophils in peritoneal cavity -flushed fluid. Conclusion：TBK1 interacts with NLRC4，phosphorylates the NLRC4 Ser533 site，and promotes the activation of NLRC4 inflammasome，which providing a theoretical basis and new potential targets for treating related diseases.

Abstract:Objective：To investigate the anticonvulsant mechanisms of bile acid monomer compounds cholic acid（CA）and deoxycholic acid（DCA）. Methods：Male SD rats were randomly divided into a control group，a model group，a sodium valproate or valproic acid（VPA），（189 mg/kg），a CA group（60 mg/kg），and a DCA group（60 mg/kg），with nine rats in each group. The rats in the control group and model group were given placebo，and the mice in each treatment group was pre -treated 1 h before modeling，and continuously treated for 16 d. A seizure rat model was established using a water bath at（45.0±0.5）℃，with a bath given every other day for a total of eight times. The seizure onset time，seizure termination time，and the severity of seizure behavior of rats were observed and recorded. Meanwhile，the levels of interleukin 1β（IL-1β），interleukin 6（IL-6），and tumor necrosis factor α（TNF-α）in rat serum and hippocampal tissues，as well as the contents of glutamate（Glu）and γ-aminobutyric acid（GABA）in hippocampal tissues were detected. Hematoxylin-eosin（HE）staining was used to observe the pathological damage of hippocampal neurons. Metabolomic analysis of rat serum was performed using the ultra-high performance liquid chromatography -tandem mass spectrometry（UHPLC -MS/MS）. Results：Compared with the model group，all treatment groups significantly prolonged the latency of seizures but significantly reduced the duration of seizures（P < 0.001）；both the VPA group and DCA group significantly reduced the severity of seizures（P < 0.001， P < 0.01），while there was no significant difference in the CA group. Compared with the control group，the contents of IL-1β TNF-α， and IL-6 in serum and hippocampal tissues of the model group were significantly increased（P < 0.001），and the contents of Glu and GABA in hippocampus were also significantly increased（P < 0.001）. Compared with the model group，the effects produced by the DCA group and the VPA group were similar，both of which reduced the levels of various biochemical indicators（P < 0.001），while the CA group significantly reduced all indicators except the TNF-α level in serum and the IL-6 level in the hippocampus（P < 0.01）. HE staining results of hippocampal tissues showed that compared with the control group，the pyramidal cells in the hippocampus of rats in the model group were contracted，with a smaller volume，a darker staining，an enhanced alkalinity，and the unclear cytoplasmic nuclear boundaries；compared with the model group，the morphology of hippocampal neurons in each treatment group was significantly improved. Among them，the morphology of hippocampal neurons in the DCA group was similar to that in the VPA group. A total of 312 differential compounds were identified in serum metabolomics analysis. Through principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS -DA）analysis，nine differential compounds were selected. The results of metabolic pathway enrichment showed that the anticonvulsant effects of CA and DCA were mainly involved the citric acid cycle，amino acid metabolism，and butyric acid metabolism pathways. Conclusion：CA and DCA have certain improvement effects on behavioral and biochemical indicators of rats with febrile seizures，and their mechanisms of action may be correlated with energy metabolism，amino acid metabolism，and short-chain fatty acid metabolism during seizures.

Abstract:Objective：To explore the role and mechanism of heat shock protein A12A（HSPA12A）in hepatic injury induced by endotoxemia. Methods：①The mRNA expression changes of Hspa12a and multiple apolipoproteins were analyzed by bioinformatics using a public database of RNA sequencing results from septic mice liver tissue. ② Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide（LPS，5 mg/kg）using 6-8-week -old Hspa12a knockout（Hspa12a^-/-）mice and wild -type（WT）mice. Mice treated with normal saline（NS）served as controls. Animals were divided into four groups，NS-WT group，NS-Hspa12a^-/- group， LPS-WT group，and LPS-Hspa12a^-/- group. Six hours after LPS treatment，liver tissues were collected to evaluate the tissue damage by HE and analyze the expression levels of HSPA12A，ApoA1，ApoB，and ApoM by immunoblotting and RT-PCR. Serum was separated for measuring the levels of liver function markers（alanine aminotransferase，ALT；aspartate aminotransferase，AST）and lipoproteins （high-density lipoprotein cholesterol，HDL-C；low-density lipoprotein cholesterol，LDL-C）. ③Primary hepatocytes overexpressed Hspa12a were treated with LPS（500 ng/mL）to emulate endotoxemia induced liver injury. Six hours after LPS treatment，culture medium was collected for measuring levels of ALT and AST. ④Patients were divided into the sepsis induced liver injury group and the control group according to whether the septic liver injury occurred. ALT，AST，HDL-C and LDL-C levels were collected and compared between the two groups. Results：①Bioinformatic analysis showed that the levels of Hspa12a，Apoa1，Apob and Apom mRNA were decreased in livers of septic mice. ②Compared with NS -WT mice，LPS -WT mice displayed obvious histopathological injury in liver tissues（P < 0.001）and the number of inflammatory foci was increased（P < 0.01）along with the elevated serum ALT（P < 0.05）and AST（P < 0.01）activiaties. At the same time，the expression of HSPA12A protein in liver was decreased（P < 0.05）. However， compared with LPS -WT mice，LPS -Hspa12a^-/- mice showed more severe pathological damage of liver tissues（P < 0.05），along with higher ALT（P < 0.01）and AST（P < 0.05）levels and lower HDL-C and LDL-C levels（P < 0.01）. At the same time，the expression levels of hepatic apolipoproteins（ApoA1，ApoB，ApoM）were reduced（P < 0.05，P < 0.01）. ③In vitro，ALT and AST levels in culture medium of hepatocytes were signaficantly increased after LPS treatment（P < 0.001）. However，overexpression of Hspa12a alleviated the increases of ALT and AST levels（P < 0.01）. ④Clinical results suggested that compared with the control group，the sepsis induced liver injury group showed signaficantly higher serum ALT and AST levels（P < 0.001）. In contrast，HDL -C and LDL -C levels were signaficantly lower（P < 0.001）. Conclusion：Endotoxemia leads to downregulation of hepatic HSPA12A expression，which mediates the development of endotoxemic liver injury. However，overexpression of Hspa12a can protect liver injury induced by endotoxemia. The action of HSPA12A may involve the regulation of hepatic apolipoprotein expression and serum lipoprotein cholesterol levels.

Abstract:Objective：To evaluate the effect of laparoscopic sleeve gastrectomy（LSG）on the psychological and quality of life of young obese patients with acanthosis nigricans（AN）and explore the mechanism. Methods：Clinical data of 52 young AN patients who underwent LSG surgery at Shanghai Tenth People's Hospital from January 2020 to December 2022 were retrospectively collected，and 50 healthy individuals were selected as the control group（CON）. The Beck self-rating depression scale -Ⅱ was used to evaluate the psychological status，and the Chinese version of SF-36 was used to evaluate the quality of life of the subjects. The anthropometries parameters，glucose metabolic indicators，lipid metabolism indicators，and C-reactive protein（CRP）levels of AN patients were evaluated and calculated before and 12 months after surgery，and compared before and after surgery. Correlation analysis was performed between depression and related metabolic indicators. Results：The scores of each dimension of quality of life assessment in the AN group before surgery were significantly lower than those in the CON group（P < 0.05），and the incidence of depression（63.5%） was significantly higher than that in the CON group（P < 0.001），with a significantly higher severity of depression than the CON group （P < 0.001）. The levels of fasting insulin，insulin resistance，blood lipids and CRP of the AN group before surgery were significantly higher than those of the CON group（P < 0.05）. Twelve months after surgery，as the weight of AN patients decreased，blood lipids and CRP levels significantly decreased，and their hyperinsulinemia and insulin resistance significantly improved. Meanwhile，the mental health score in the SF-36 scale of AN patients significantly increased，and the depression score and severity also significantly improved. Depression scores in patients were positively correlated with body mass index，insulin resistance，and CRP. Conclusion： Depression in AN patients is closely related to increased insulin resistance and inflammatory factors. LSG effectively improves depression and quality of life in AN patients by reducing weight，improving insulin resistance，and inflammation.

Abstract:Objective：To investigate the expression of cutaneous T cell lymphoma associated antigen 15（CTAGE15）and its association with clinical prognosis of esophageal squamous cell carcinoma（ESCC）patients，as well as its effect on the proliferation， migration，and invasion abilities of ESCC cells. Methods：Kaplan -Meier analysis was used to analyze the effect of CTAGE15 on the prognosis of ESCC patients in public database. The mRNA expression levels of CTAGE15 in esophageal epithelial cells and ESCC cells were measured by qRT-PCR. Furthermore，the expression of CTAGE15 was detected in cancer and adjacent normal tissues from 120 ESCC patients with a complete follow-up information. COX proportional survival risk model was enrolled to analyze the survival risk factors of ESCC patients，and multivariate correlation analysis was used for the analysis of the association between CTAGE15 expression and the clinicopathology of ESCC patients. Kaplan-Meier analysis was employed to analyze the effect of CTAGE15 on the prognosis of ESCC patients. The knockdown of CTAGE15 in ESCC cells was achieved by using small interfering RNA（siRNA），and the changes in cell proliferation，migration，and invasion abilities of ESCC cells were assessed. Results：The public database showed that the CTAGE15 expression was significantly associated with overall survival（P < 0.05）and disease-specific survival（P < 0.05）in ESCC patients，and a higher GTAGE15 expression was correlated with a better survival. The qRT -PCR results revealed significantly high expression of CTAGE15 in ESCC tissues and cells，compared with normal esophageal epithelial tissues and cells. In addition，the expression of CTAGE15 was significantly associated with T stage and N stage of ESCC patients，and a higher GTAGE15 expression was associated with an earlier T stage and N stage. Knockdown of CTAGE15 enhanced the proliferation，migration，and invasion abilities of ESCC cells（P < 0.05）. Conclusion：CTAGE15 expression is positively associated with the prognosis of ESCC patients，and it inhibits the proliferation，migration and invasion abilities of ESCC cells.

Abstract:Objective：To explore the expression and significance of arachidonate 12-lipoxygenase（ALOX12）in cancer tissues of colon cancer patients. Methods：Tumor and peritumoral tissues of 257 colon cancer patients were retrospectively collected，and the expression of ALOX12 was detected by immunohistochemistry（IHC）to compare the differences in expression within the tumor and peritumoral tissues，and the relationship between ALOX12 expression and clinicopathological features of colon cancer was analyzed. The 5-year overall survival（OS）of the patients was analyzed using Kaplan-Meier curves，and the factors affecting the 5-year OS of the patients were investigated by univariate and multivariate Cox regression analyses. Results：ALOX12 was more positively expressed in tumors compared to peritumoral tissues（63.8% vs. 33.1%），and the difference was statistically significant（P < 0.001）. The expression of ALOX12 was not significantly correlated with the patient’s age，gender，and tumor site（P > 0.05），but was strongly correlated with TNM staging and lymph node metastasis（P < 0.05）. Five-year OS of patients with high expression of ALOX12 was markedly lower than those patients with low expression of ALOX12（P < 0.001）. Single variable and multivariate Cox analyses indicated that age，TNM staging，lymph node metastasis，and ALOX12 expression were independent factors influencing the 5-year OS rate（P < 0.05）. Conclusion：High expression of ALOX12 is associated with TNM staging and lymph node metastasis of colon cancer，which can serve as a biomarker to predict the patient’s condition and prognosis.

Abstract:Objective：To evaluate the early clinical outcomes of no-touch harvesting technique and conventional harvesting technique applied to off -pump coronary artery bypass grafting. Methods：The clinical data of 120 patients who underwent off -pump coronary artery bypass grafting from July 2020 to July 2022 in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed，of which 50 cases used no-touch harvesting technique（No-touch group） and 70 cases used conventional harvesting technique（CVH group）. Observation indexes included operation time，number of vein graft， average flow rate of vein graft，ventilation time，ICU stay，postoperative complications such as poor healing of leg wound and postoperative acute kidney injury，as well as echocardiographic indexes and coronary CT angiography results after 1 year of follow-up. Results：There was no statistically significant difference in operation time，number of vein graft，average flow rate of vein graft，ventilation time and ICU stay between the two groups（P > 0.05）. In the No-touch group，there were 5 cases of intra-aortic balloon pump（IABP）support， 2 cases of poor healing of leg wound，and 1 case of postoperative cardiac event. In the CVH group，there were 2 cases of postoperative IABP support and 1 case of postoperative acute kidney injury. There were no cases of reoperation and reintubation in the two groups， and the difference in the incidence of postoperative complications was not statistically significant（P > 0.05）. There was no statistically significant difference in the postoperative echocardiographic indexes between the two groups at 1 year after surgery（P > 0.05）. The rate of vein graft occlusion in the No -touch group was lower than that in the CVH group at 1 year after surgery，and the difference between the two groups was statistically significant（P < 0.05）. Conclusion：Compcued with conventional harvesting technique，the use of no-touch harvesting technique for saphenous vein harvesting in off-pump coronary artery bypass grafting does not increase the surgical risk，and the patency rate of vein graft is high at 1 year after surgery.

Abstract:Objective：To analyze the risk factors for moderate to severe abdominal pain in patients with hepatocellular carcinoma （HCC）after their first transarterial chemoembolization（TACE）and to establish a predictive model. Methods：A total of 219 HCC patients who underwent first-time TACE in our hospital between January 2021 and June 2023 were collected. Based on the chronological order of receiving TACE treatment，the patients were divided into a training set（154 cases）and a validation set（65 cases）in a 7∶3 ratio. The training set patients were further categorized into the moderate to severe abdominal pain group and the non-moderate to severe abdominal pain group based on whether moderate to severe abdominal pain occurred after TACE，and demographic and clinical characteristics were compared between the two groups. Logistic regression analysis was used to analyze the risk factors for moderate to severe abdominal pain after the first TACE treatment in HCC patients and to construct a predictive model. The receiver operator characteristic（ROC）curve method was used to evaluate the predictive performance of the model in the training and validation sets for the occurrence of moderate to severe abdominal pain after TACE. Results：In the training set of 154 cases，42 cases（27.3%）of HCC patients experienced moderate to severe abdominal pain after TACE. Logistic regression revealed that tumor distance from the liver capsule ≤1 cm（P=0.001），iodized oil usage >10 mL（P < 0.001），and the use of non-alcoholic ethanol embolization（P=0.007）were independent risk factors for moderate to severe abdominal pain after the first TACE treatment in HCC patients. The predictive model was 2.199×tumor distance from the liver capsule + 2.252×iodized oil usage + 1.637×use of nonalcoholic ethanol-3.829. The ROC curve areas for predicting moderate to severe abdominal pain in the training and validation sets were 0.895 and 0.853， respectively. Conclusion：Tumor distance from the liver capsule ≤1 cm，iodized oil usage >10 mL，and the use of nonalcoholic ethanol embolization are risk factors for moderate to severe abdominal pain in HCC patients after their first TACE treatment. The predictive model can provide guidance for the management of moderate to severe abdominal pain in HCC patients after their first TACE.

Abstract:Objective：To investigate the predictive value of three preoperative inflammatory markers for lymph node metastasis in patients with pT1a stage penile squamous carcinoma without palpable inguinal lymph nodes. Methods：Clinical data of 103 patients with pT1a stage penile squamous carcinoma admitted to the First Affiliated Hospital of Soochow University and Taixing People’s Hospital from January 2012 to June 2023 were collected. Patients were divided into lymph node metastasis group and non-lymph node metastasis group based on postoperative pathological findings of inguinal lymph node involvement. Differences in age，body mass index （BMI），hypertension，diabetes mellitus，tumor diameter，neutrophil-to-lymphocyte ratio（NLR），platelet-to-lymphocyte ratio（PLR）， lymphocyte-to-monocyte ratio（LMR），and postoperative pathological grading were compared between the two groups. Independent risk factors for lymph node metastasis were screened using univariate and multivariate logistic regression analyses. Receiver operating characteristic（ROC）curves were performed to compare the predictive value of inflammatory markers for lymph node metastasis in patients with pT1a stage penile squamous carcinoma，and the predictive efficacy of each inflammatory markersfor lymph node metastasis was evaluated after adjusting sensitivity to 100% . Results：There were 24 cases（23.3%）in the inguinal lymph node metastasis group and 79 cases（76.7% ）in the non-lymph node metastasis group. The differences between the two groups were statistically significant in terms of NLR（P < 0.001），PLR（P=0.035），and LMR（P < 0.001）. Multivariateanalysis showed that NLR（P= 0.045）and LMR（P=0.021）were independent risk factors for inguinal lymph node metastasis in pT1a stage penile cancer. ROC curve analysis results showed that the area under the curve for NLR，LMR，and NLR+LMR were 0.833，0.816，and 0.835 respectively. The optimal cut-off value for NLR was 2.33，with a sensitivity of 95.8% and a specificity of 68.4%；the optimal cut-off value for LMRwas 3.80，with a sensitivity of 79.2% and a specificity of 78.5%；the sensitivity and specificity of combined detection of NLR+LMR were 83.3% and 74.7%，respectively. When adjusting sensitivity to 100%，the specificity of NLR and LMR for predicting inguinal lymph node metastasis in pT1a stage peniles quamous carcinoma was 50.6% and 2.5%，with cut-off values of 1.79 and 11.01. Conclusion： NLR and LMR are independent predictive factors for inguinal lymph node metastasis in pT1a stage penile squamous carcinoma. NLR> 2.33 and LMR＜3.80 suggest that patients are at great risk of lymph node metastasis，and lymph node dissection surgery is recommended to improve patient survival.

Abstract:Objective：To evaluate the safety and feasibility of transversus thoracic muscle plane-pectoral nerves（TTP-PECS）block in modified radical mastectomy for breast cancer under opioid-sparing general anesthesia. Methods：Sixty patients scheduled for modified radical mastectomy for breast cancer were randomly divided into two groups：the TTP-PECS block combined with opioid-sparing general anesthesia group（TO group）and the conventional general anesthesia group（GA group），with 30 patients in each group. The systolic blood pressure（SBP），diastolic blood pressure（DBP），and heart rate（HR）of the two groups were observed and recorded at various time points；the pain visual analogue scale（VAS）scores at rest and on movement were recorded at anesthesia induction（T₀）， just before intubation（T₁），at skin incision（T₂），at breast specimen removal（T₃），and at the end of surgery（T₄）；and the quality of recovery-40（QoR-40）scores were assessed 24 h postoperatively. The incidence of adverse events during the perioperative period was also recorded. Results：Compared with T0，the SBP，DBP，and HR of both groups were significantly decreased at T₁-T₄（P < 0.05），but there was no statistically significant difference between the two groups at each time point（P > 0.05）. The VAS scores at 2 h，6 h，and 12 h postoperatively，both at rest and on movement，were significantly lower in the TO group than in the GA group（P < 0.05）. The total QoR -40 scores and scores for emotional state，physical comfort，psychological support，and pain were significantly higher in the TO group than in the GA group 24 h postoperatively（P < 0.05）. The incidence of cough reflex during induction and postoperative nausea and vomiting were significantly lower in the TO group than in the GA group（P < 0.05）. Conclusion：TTP-PECS block combined with opioid-sparing general anesthesia is safely used in modified radical mastectomy for breast cancer，providing effective postoperative analgesia，reducing the incidence of postoperative nausea and vomiting，and improving early recovery quality for patients.

Abstract:Objective：To utilize machine learning algorithms to predict risk factors affecting the activities of daily living（ADL）of stroke patients，providing references for their ADL management decisions. Methods：A retrospective analysis was conducted on 423 stroke patients treated at the Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University from January 2015 to February 2019. Patients were categorized into a better ADL group（BI ≥ 60 points）and a poorer ADL group（BI <60 points） based on the Barthel Index（BI）assessment scale，and data preprocessing was performed. Feature variables were selected using colinearity diagnostics and the least absolute shrinkage and selection operator（LASSO）. Logistic regression（LR），support vector machine（SVM），random forest（RF），extreme gradient boosting（XGBoost），and K nearest neighbor（KNN）were selected as the five machine learning algorithms for predictive modeling. Afterten-fold cross-validation，the models were comprehensively evalutated using receiver operating characteristic（ROC）curves，area under aerue（AUC），precision recall（PR）curves，area under the precision recall curve（PRAUC），accuracy，sensitivity，and specificity. The Shapley additive interpretation（SHAP）was introduced to interpret the optimal machine learning model. Results：After LASSO regression analysis，16 feature variables were identified for constructing the machine learning model. The RF model demonstrated superior performance with the highest AUC（0.74），PRAUC（0.64），accuracy （0.97），sensitivity（0.75），and specificity（0.97）. Interpretive analysis of the SHAP model revealed that among the top 5 features contributing to ADL，Brunnstrom stage（lower limb）exerted the most significant effect，followed by Brunnstrom stage（upper limb），D-dimer，serum albumin level，and age. Conclusion：The RF model emerged as the most effective in predicting ADL in stroke patient， providing valuable references for ADL management decisions in stroke patients.

Abstract:Objective：To investigate the prognostic correlation between mitochondrial DNA（mtDNA）content and colorectal cancer. Methods：Clinical and pathological data were collected from 117 patients with colorectal cancer. RT-qPCR was used to determine the mtDNA content of cancer tissues and paracancerous tissues of patients，and the correlation between mtDNA content and various prognostic indicators was investigated. Receiver operating characteristic（ROC）curves were plotted，and the cut-off value was determined to distinguish patients，and disease free survival（DFS）curves were plotted accordingly. Univariate and multivariate Cox regression analyses were conducted to explore the risk factors related to postoperative DFS. Results：There was no significant difference in mtDNA content between cancer tissues and paracancerous tissues（P=0.432）；low mtDNA content was associated with tumor location in the colon，poor differentiation，advanced TNM stage，and lymph node metastasis（P < 0.05）. The ROC curve indicated a cut-off value of 500.699 for mtDNA content. Univariate and multivariate Cox analyses showed that mtDNA content lower than 500.699 （HR=4.285，95%CI：1.938-9.475）and poorly differentiated tumors（HR=2.886，95%CI：1.428-5.835）were independent risk factors associated with DFS. Conclusion：In patients with colorectal cancer，tissue mtDNA content is associated with clinical and pathological characteristics，and low mtDNA content is an independent risk factor for patient prognosis.

Abstract:The small molecule alkylating agent temozolomide（TMZ）is commonly used as a frontline therapy for glioblastoma （GBM）. However，there are certain factors，such as the presence of O-6-methylguanine-DNA methyltransferase（MGMT）and activated DNA repair pathways，that can lead to resistance to TMZ，thereby limiting its effectiveness. This paper aims to comprehensively review the detailed molecular mechanisms of TMZ resistance，discuss innovative therapeutic strategies to overcome resistance，and explore potential drugs that may enhance the efficacy of TMZ. Ultimately，our goal is to provide valuable insights into clinical approaches for mitigating TMZ resistance in GBM patients.

Abstract:Alzheimer’s disease（AD）is the most common type of neurodegenerative disorder. Mounting evidence suggest that genetic factors play crucial roles in the pathogenesis of AD. The triggering receptor expressed on myeloid cells 2（TREM2）gene is a recently identified susceptibility gene for AD. Here，our previous findings and the recent high-quality studies are comprehensively reviewed regarding the association of TREM2 variants with AD risk，the structure，ligand and downstream signaling of TREM2，the involvement of TREM2 in AD progression，and targeting TREM2 for AD treatment. This review will offer further insights into the genetic and pathogenic mechanisms of AD and provide reference for the development of novel AD therapies.

Abstract:Mitochondria are an indispensable component of multicellular life. They undergo morphological changes and spatial rearrangement to meet the needs of cells and maintain energy balance through fusion and fission，a process called mitochondrial dynamics. A large number of studies have shown that mitochondria participate in a variety of cell biological processes such as apoptosis，cell proliferation，cell migration，and energy metabolism through fusion and fission. In recent years，respiratory diseases have become a major global health problem. Recent studies have found that mitochondrial dynamics disorder plays an important role in the formation of many respiratory diseases. The study of mitochondrial dynamics disorders provides a new perspective for the formation mechanism of respiratory diseases.

Abstract:Follicular fluid is the internal environment where follicular cells grow and proliferate，and the changes of its components are closely related to the functional status of follicular cells. In recent years，it has been found that exosome，a double-layer membrane vesicle with a diameter of about 30-150 nm，exists in many biological fluids，and its mediating role in many physiological and pathological processes has been revealed. The researchers also identified exosomes in follicular fluid and found that they are closely related to the growth and proliferation of follicular cells，indirectly influencing oocyte status，which is important for assessing oocyte quality.

Abstract:With changes of human disease spectrum，obesity and its complications have become important health risk factors. Under normal physiological conditions，there is a certain amount of lipid droplets in skeletal muscle，known as intramuscular fat. However， when the body becomes obese，the rate of lipid droplet generation exceeds consumption，leading to the overload of adipose tissue and resulting in ectopic fat deposition. This excessive accumulation of intramuscular fat severely disrupts the normal function of skeletal muscle and plays an important role in the occurrence and development of sarcopenia，obesity and diabetes. Although the importance of intramuscular fat infiltration in obesity and related metabolic diseases is widely recognized，its specific regulatory mechanism remains unclear. Therefore，exploring new strategies and methods to improve intramuscular fat infiltration not only helps us to better understand the pathogenesis of these diseases but also provide new perspectives for the treatment of these diseases. The core content of this article lies in comprehensively elucidating the physiological functions of intramuscular fat tissue and the mechanisms leading to intramuscular fat infiltration under pathological conditions. Additionally，the research progress on the intervention for intramuscular fat infiltration is reviewed，aiming to provide potential therapeutic strategies for the treatment of clinical diseases related to intramuscular fat infiltration.

Abstract:Breast cancer is currently the most common tumor worldwide，and early detection and diagnosis are of great significance for the treatment and prognosis of breast cancer patients. Dedicated breast PET（dbPET）is an emerging molecular imaging device that has been used in clinical practice for the detection of breast cancer and the assessment for tumor biology. It has higher spatial resolution than conventional imaging modalities and can identify detailed morphological patterns of radiotracer uptake within the breast. There have been few comprehensive analysis of dbPET both domestically and internationally. In this paper，we review dbPET in breast cancer screening，diagnosis，uptake patterns，assessment after neoadjuvant chemotherapy，and PET imaging agents to provide a systematic understanding of dbPET.

Abstract:Pituitary adenomas secreting adrenocorticotropin hormone（ACTH），known as ACTH-secreting pituitary adenomas，cause hypercortisolism by overproducting ACTH and stimulating bilateral adrenal cortical hyperplasia，a condition also known as Cushing’s disease（CD），which is the most common cause of endogenous hypercortisolism. ACTH-secreting pituitary adenomas lead to a series of severe clinical syndromes，including electrolyte disturbances and disorders of glucose and lipid metabolism，affecting multiple organs and systems throughout the body. Transsphenoidal neuroendoscopic surgery is the first -line treatment for ACTH-secreting pituitary adenomas，with a high remission rate，but postoperative recurrence and persistent disease remain unsolved in the treatment of ACTH-secreting pituitary adenomas. The pathological evaluation of ACTH-secreting pituitary adenomas has important value in determining the nature of the lesions，predicting the prognosis，and selecting the drug therapy. This article reviews the advances in the pathologic evaluation of ACTH-secreting pituitary adenomas，including new immunohistochemical markers and microscopic special features.

Abstract:In the recent years，as the center of energy metabolism，the role of hypothalamus in the development of obsity has been increasingly emphasised. Hypothalamic neural stem cells（htNSCs）which control adult neurogenesis play a crucial role in sensing the metabolic state of the body and maintaining energy balance by altering differentiation pathways，exosome functions，and mitigating inflammatory. By studying the hypothalamus and htNSCs，we can gain a better understanding of the mechanisms behind energy metabolism disorders in obesity and identify potential therapeutic targets for obesity and metabolic syndrome.