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.

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.

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 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:To investigate the application value of hand-sewn esophagojejunal anastomosis (EJA) in totally laparoscopic total gastrectomy (TLTG).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 35 patients with early or advanced upper gastric cancer who were admitted to Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine between July 2018 and December 2019 were collected. There were 24 males and 11 females, aged (60±10)years, with a range of 35-75 years. All the 35 patients underwent TLTG combined with hand-sewn EJA. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) postoperative pathological examination; (4) follow-up and survival. Follow-up was conducted using telephone interview, outpatient examination, short message service and WeChat to detect tumor recurrence, metastasis and survival of patients up to January 2020.Measurement data with normal distribution were repressented as Mean± SD. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absoulte numbers or persentages. Results:(1) Intraoperative situations: all the 35 patients underwent TLTG combined with hand-sewn EJA successfully. The operation time, volume of intraoperative blood loss, time of hand-sewn EJA, costs of consumables used in the intraoperative resection and reconstruction, and costs of consumables used in EJA of the 35 patients were 305 minutes(range, 232-406 minutes), 94 mL(range, 50-300 mL), 37 minutes(range, 20-65 minutes), 13 674 yuan(range, 11 929-15 255 yuan) and 491 yuan(range, 223-1 044 yuan), respectively. Of the 35 patients, 4 received intraoperative blood transfusion. (2) Postoperative situations: time to first out-of-bed activity, postoperative indwelling time of gastric tube, time to initial liquid diet intake, the time to abdominal drainage tube removal and duration of postoperative hospital stay of the 35 patients were 2 days(range, 1-3 days), 4 days(range, 2-11 days), 5 days(range, 4-12 days), 8 days(range, 5-15 days) and 9 days(range, 7-16 days), respectively. Of the 35 patients, 3 had perioperative complications. One patient had inflammation and infection in the pancreatic tail and was discharged at postoperative 16 days after conservative treatment of fasting, somatostatin to reduce the pancreatic secretion, adequate drainage, anti-infection and nutritional support. One had postoperative intestinal incomplete obstruction and was discharged at postoperative 12 days after treatment with gastrointestinal decompression and enema for relief of obstruction. One had pulmonary infection who was discharged at postoperative 9 days after symptomatic and supportive treatment. None of the 35 patients had perioperative anastomotic leakage or bleeding. Of the 35 patients, 1 was diagnosed with esophagojejunostomy stenosis at postoperative 2 months and was improved after endoscopic dilatation. The incidence of long-term anastomosis-related complications of the 35 patients was 2.9%(1/35). (3) Postoperative pathological examination: the pathological examination of the upper margin of intraoperative frozen section and postoperative paraffin section showed negative in the 35 patients. Of the 35 patients, 16 had tumor located at cardia including 4 cases with tumor involving in lower esophagus, 19 had tumor located at stomach; 21 had tumor pathological type as highly or moderately differentiated adenocarcinoma, 11 had poorly differentiated adenocarcinoma, 3 had signed-ring cell carcinoma; 14 had early gastric cancer, 21 had advanced gastric cancer; 7 had tumor invaded at mucosa lamina propria and muscularis, 7 had tumor invaded at submucosa, 1 had tumor invaded at muscularis, 1 had tumor invaded at subserosal, 17 had tumor invaded at serosal, 2 had tumor invaded at extra-serosal adipose tissue. The TNM staging of the 35 patients: 14 were in stage ⅠA , 2 in stage ⅠB, 4 in stage ⅡB, 3 in stage ⅢA, 4 in stage ⅢB and 8 in stage ⅢC. Of the 35 patients, 15 had vascular invasion and 16 had nerve invasion. The tumor diameter, the number of lymph nodes dissected and the number of positive lymph nodes of the 35 patients were 3.9 cm(range, 0.6-12.0 cm), 24(range, 10-40) and 2(range, 0-11). (4) Follow-up and survival: all the 35 patients were followed up for 1-18 months, with a median time of 5 months. Of the 35 patients, tumor recurrence or metastasis was not found in 34 patients, and the other 1 patient was diagnosed with liver metastases of tumor at postoperative 6 months and survived with tumor.Conclusion:Hand-sewn EJA in TLTG is safe and feasible.

Objective:To observe the effect of hypoxia on the dedifferentiation process of chondrocytes in vitro and explore the role of collagen prolyl 4-hydroxylase (C-P4Hs).Methods:Chondrocytes were treated with COCl 2 for different concentrations, and selecting the optimal COCl 2 concentration for hypoxia inductionwas100 μmol/L, the mouse costal chondrocytes were divided into the normal oxygen group and the hypoxia group, and the indexes of the 3rd generation 0.5-72 h and the 1st, 3rd, 5th and 7th generation at 72 h were detected respectively. The proliferation rate was determined by CCK8 method and cell count, and the dynamic changes of HIF-1α, P4Hα1, P4Hα2 and Col II in each group were detected by RT-qPCR, IF and Western blot. Results:Costal chondrocytes were cultured under different concentration of COCl 2 for 48 h. When COCl 2>150 μmol/L, the proliferation rate ( P<0.05) was significantly decreased. Normal oxygen and hypoxia induced rib chondrocytes for 0-72 h, and RT-qPCR showed significant increases in P4Hα2 and Col II mRNA in hypoxia group ( P<0.05). IF showed that HIF-1α and P4Hα2 accumulated in the nucleus under hypoxia, and P4Hα2 gradually entered the cytoplasm from the nucleus. Westernblot analysis showed that HIF-1α and P4Hα2 protein expressions were significantly increased in hypoxia group ( P<0.05). The expression of Col II protein in hypoxia group ( P<0.05) increased at the induction stage. CCK8 and cell count results showed that the proliferation rate and cell number of each generation in the hypoxic group were significantly increased ( P<0.05), and there was still potential for proliferation when the cells were transferred to the 6-7 generation. RT-qPCR showed that hypoxia group each generation cells P4Hα2, Col II mRNΑ were significantly increased ( P<0.05). Westernblot results showed that HIF-1α, P4Hα2 and Col II protein expressions were increased in each generation of hypoxia group ( P<0.05). ConcIusion:Increased expression of P4Hα2 through hypoxia induced HIF-1α can accelerate post-translational modification of Col II in chondrocytes and increase synthesis and accumulation of Col II. P4Hα2 may be responsible for increased proliferation rate and delayed dedifferentiation of chondrocytes cultured in vitro under hypoxia condition.