As one of the core pathogenesis during treatment with traditional Chinese medicine，liver heat runs through different stages of liver disease. The interpretation of its meaning in different medicine categories（traditional Chinese medicine，Tibetan medicine，Mongolian medicine，Uygur medicine，Dai medicine，Yao medicine，etc.） is not unified， and the phenomena of the same name with different meanings，confusion， and misappropriation emerge. This seriously restricts the inheritance，innovation， and clinical application of traditional Chinese medicine and ethnomedicine. By tracing and analyzing liver heat， it is found that liver heat in traditional Chinese medicine is caused by disordered rest and diet， as well as internal injury due to emotional disorder， which leads to liver dysfunction， Qi stagnation， and heat turning to fire in the liver meridian. The liver heat in Tibetan medicine is caused by the accumulated heat of the liver nature and the evil heat in the liver， which stimulates the toxin of Chiba fever. The liver heat in Mongolian medicine derives from the abnormal diet and rest， making excessive Sheila accumulate in the liver and causing disease. The above etiologies are all related to diet， rest，exogenous evil，emotion，and so on， and the pathogenesis is related to the imbalance of Qi and the metabolic disorder of organs. The clinical symptoms are pain in the liver region，yellow eyes， bitter mouth， fever，digestion，and loss of appetite. The principle of treatment and compatibility of prescription are heat-based， with auxiliary detoxification. Other ethnomedicine， such as Uygur medicine， Dai medicine， Yao Medicine，Miao medicine， and She medicine do not have a clear discussion on liver heat，and their etiology， pathogenesis， treatment，and prescription are not systematic，mostly based on a single drug or proven prescriptions.Through the systematic tracing，mining，induction，analysis， and arrangement of the liver heat based on existing literature information database in China，this paper regarded syndrome as the outline and disease as the goal，clarified the similarities and differences of the pathogenesis of liver heat in traditional Chinese medicine，and determined the relationship between liver heat and liver disease and the status quo of syndrome and treatment.This review provides evidence and reference for clinical prevention and treatment，as well as drug development for liver disease.

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

Mitochondrial diabetes mellitus (MDM) is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) or nuclear DNA mutations, characterized by multi-system involvement and diverse clinical phenotypes. We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus. Systematic evaluation revealed concurrent bilateral sensorineural hearing loss, bilateral basal ganglia calcification, and electroencephalographic abnormalities. A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion. Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084. This case report is complemented by a literature review focusing on the pathogenesis, genetic characteristics, and therapeutic approaches of mitochondrial diabetes, with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations. Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest(RF),extreme gradient boosting(XGBoost),light gradient boosting machine(LightGBM),and categorical boosting(CatBoost).Methods We obtained the ex-pression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prog-nosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost mod-els were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation.Results A total of 151 differentially expressed protein-coding genes related to survival prog-nosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance.Conclusions Three protein-coding genes(UGP2,C3orf80,and SPC25)were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.

Objective:To collect and analyze the evaluation index of infertility treated by Traditional Chinese Medicine (TCM), which will lay a foundation for the establishment of the core index and evaluation index system of TCM treating infertility.Methods:By retriving the published literatures of randomized controlled trials of infertility treated by TCM in the database of CNKI, VIP, Wanfang, SinoMed, PubMed and Cochrane Library from January 1, 2011 to December 31, 2020, and after the screening according to the creteria of inclusion and exclusion, this paper analyzed the normal indexes of infertility and the pathogenic indexes of TCM.Results:A total of 95 RCTs were included, including 9 069 patients aged between 20-39 years old. The average sample size of each RCT study was 95, involving 78 evaluation criteria. The highest frequency of use was the total effective rate, etiological-index analysis found that the general indicators of infertility such as the total effective rate, pregnancy rate, TCM syndrome scores,and common etiological factors such as LH, FSH are the characteristic indicators.Conclusion:There are many problems in the evaluation indexes of clinical trials of treating infertility by TCM, such as great differences in number and not standardized usage. It is necessary to carry out research on the construction of core indicator and evaluation indicator systems of infertility according to different etiologies.

Objective:To investigate the short-term efficacy of laparoscopic total gastrec-tomy with hand-sewn esophagojejunostomy versus Roux-en-Y anastomosis.Methods:The propen-sity score matching and retrospective cohort study was conducted. The clinicopathological data of 159 patients who underwent laparoscopic total gastrectomy in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to July 2021 were collected. There were 107 males and 52 females, aged 63(range, 28?79)years. Of 159 patients, 71 cases undergoing totally laparoscopic total gastrectomy with hand-sewn esophagojejunostomy were allocated into totally laparoscopic group and 88 cases undergoing laparoscopic-assisted total gastrectomy with Roux-en-Y anastomosis were allocated into laparoscopic-assisted group, respectively. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability method. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 159 patients, 112 cases were successfully matched, including 56 cases in the totally laparoscopic group and 56 cases in the laparoscopic-assisted group. Before propensity score matching, age, cases with tumor located in cardia or gastric body in the totally laparoscopic group were 61(range, 30?76)years, 26, 45, respectively. The above indicators in the laparoscopic-assisted group were 65(range, 28?79)years, 50, 38, respectively. There were significant differences in the above indicators between the two groups ( Z=?2.89, χ2=6.43, P<0.05). After propensity score matching, the males and females, age, body mass index, cases of American Society of Anesthesiologists classification Ⅰ, Ⅱ, Ⅲ and Ⅳ, tumor diameter, cases with tumor located in cardia or gastric body, cases in TNM stage Ⅰ, Ⅱ and Ⅲ of patients in the totally laparoscopic group were 40, 16, (62±9)years, (22.7±2.8)kg/m 2, 22, 26, 7, 1, 3.5(range, 0.6?17.0)cm, 24, 32, 22, 9, 25. The above indicators of patients in the laparoscopic-assisted group were 38, 18, (62±10)years, (22.7±3.2)kg/m 2, 19, 32, 5, 0, 4.0(range, 0.6?15.0)cm, 23, 33, 21, 7, 28, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.17, t=?0.09, ?0.04, Z=?0.12, ?0.82, χ2=0.04, Z=?0.42, P>0.05). The elimination of age and tumor location confounding bias ensured comparability between the two groups. (2) Intraoperative and postoperative conditions: after propensity score matching, the total operation time, time of esophagojejunostomy, postopera-tive 24-hour pain numerical score and time to first out-off bed activities were (310±49)minutes, (37±10)minutes, 2.3±0.8 and (2.4±0.7)days for patients in the totally laparoscopic group, versus (344±77)minutes, (44±12)minutes, 3.1±1.2 and (2.9±1.0)days in the laparoscopic-assisted group, showing significant differences between the two groups ( t=?2.85, ?3.05, ?4.20, ?3.10, P<0.05). (3) Perioperative complications: after propensity score matching, 6 cases of the patients in the totally laparoscopic group had Clavien-Dindo grade 2 or higher complications, including 2 cases of anas-tomotic leak, 1 case of anastomotic stenosis, 1 case of pleural effusion, 1 case of abdominal infection and 1 case of intestinal obstruction. The incidence of Clavien-Dindo grade 2 or higher complications was 10.7%(6/56). In the laparoscopic-assisted group, 5 patients had Clavien-Dindo grade 2 or higher complications, including 2 cases of anastomotic leak, 1 case of abdominal infection, 1 case of intestinal obstruction and 1 case of cholangitis. The incidence of Clavien-Dindo grade 2 or higher complications was 8.9%(5/56). There was no significant difference in the incidence of Clavien-Dindo grade 2 or higher complications between the two groups ( χ2=0.10, P>0.05). Patients with anas-tomotic leak were improved after puncture and drainage, secondary surgery and conservative treat-ment, and other complications were improved after symptomatic treatment. Conclusions:Com-pared with Roux-en-Y anastomosis in laparoscopic total gastrectomy, the time of hand-sewn esophagojejunostomy and esophago-jejunal anastomosis are shorter, patients have less postopera-tive pain and faster postoperative recovery. Both methods have good peri-operative safety.

Objective: To investigate the inhibition of tanshinoneⅡA (TanⅡA) on the proliferation of lung cancer cells. Methods: Human lung cancer cell lines A549, SK-MES-1, H446 and H460 were cultured in vitro and treated with TanⅡA at concentrations of 0.3, 0.6, 1.3, 2.5, 5.0, 10.0 mg/mL, while untreated cells served as controls. Cell proliferation was measured by using CCK-8 assay, and apoptosis was measured using flow cytometry, while the expression of apoptosis-related proteins was determined using Western blotting. The apoptotic rate of lung cancer cells was compared between Tan ⅡA-treated cells and untreated cells. Results: Tan ⅡA inhibited lung cancer cell proliferation in a time-dependent and concentration-dependent manner, and the survival rates of A549, SK-MS-1, H446 and H460 cells reduced with the concentration of TanⅡA (t=4.503, 2.114, 2.103 and 3.567; all P<0.05) and the duration of TanⅡA treatment (t=5.189, 3.079, 3.023 and 3.845; all P<0.05). The 48 h half maximal inhibitory concentrations (IC50 values) of TanⅡA were (1.18±0.12), (0.78±0.08), (1.55±0.16) and (1.27±0.14) mg/mL against A549, SK-MES-1, H446 and H460 cells, respectively. Following 48 h treatment with Tan ⅡA at a concentration of 2.5 mg/mL, the apoptotic rates of A549, SK-MS-1, H446 and H460 cells were (34.97±3.78)%, (37.62±2.48)%, (18.27±2.98)% and (19.17±2.30)%, which were significantly significantly higher than those of untreated cells [(4.86±0.36) %, (3.21±0.48) %, (3.25±0.26)% and (2.66±0.19)%, all P<0.05]. Reduced Akt1 protein expression, elevated Bax/Bcl-2 expression ratio, and elevated caspase-9 and caspase-3 protein expression were detected in lung cancer cells treated with 2.5 mg/mL TanⅡA for 48 h relative to untreated cells Conclusion TanⅡA may inhibit lung cancer cell proliferation in a time- and concentration-dependent manner via the Bax/Bcl-2/caspase-9/caspase-3 pathway.

Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.