In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Purpose::Intramedullary nailing is the preferred internal fixation technique for the treatment of subtrochanteric fractures because of its biomechanical advantages. However, no definitive conclusion has been reached regarding whether combined cable cerclage is required during intramedullary nailing treatment. This study is performed to compare the clinical effects of intramedullary nailing with cerclage and non-cerclage wiring in the treatment of irreducible spiral subtrochanteric fractures.Methods::Patients with subtrochanteric fractures admitted to our center from January 2013 to December 2021 were retrospectively analyzed. The patients were enrolled in the case-control study according to the inclusion and exclusion criteria and divided into the non-cerclage group and the cerclage group. The patients' clinical data, including the operative time, intraoperative blood loss, hospital stay, reoperation rate, fracture union time, and Harris hip score, were compared between these 2 groups. Categorical variables were compared using Chi-square or Fisher's exact test. Continuous variables with normal distribution were presented as mean ± standard deviation and analyzed with Student's t-test. Nonnormally distributed variables were expressed as median (Q 1, Q 3) and assessed using the Mann-Whitney test. A p < 0.05 was considered significant. Results::In total, 69 patients were included in the study (35 patients in the non-cerclage group and 34 patients in the cerclage group). The baseline data of the 2 groups were comparable. There were no significant difference in the length of hospital stay (z = -0.391, p = 0.696), operative time (z = -1.289, p = 0.197), or intraoperative blood loss (z = -1.321, p = 0.186). However, compared with non-cerclage group, the fracture union time was shorter (z = -5.587, p < 0.001), the rate of nonunion was lower (χ 2= 6.030, p = 0.03), the anatomical reduction rate was higher (χ 2= 5.449, p = 0.03), and the Harris hip score was higher (z =-2.99, p = 0.003) in the cerclage group, all with statistically significant differences. Conclusions::Intramedullary nailing combined with cable cerclage wiring is a safe and reliable technique for the treatment of irreducible subtrochanteric fractures. This technique can improve the reduction effect, increase the stability of fracture fixation, shorten the fracture union time, reduce the occurrence of nonunion, and contribute to the recovery of hip joint function.

Traditionally,the brain was considered as an immune-privileged organ.However,the re-discoveries of meningeal lymphatic vessels have revolutionized our understanding,revealing direct physical and functional connections between the central nervous system and the peripheral immunity.Meningeal lymphatic vessels play a crucial role in draining cerebro-spinal fluid,clearing metabolic waste from the brain,eliciting immune surveillance and maintaining immune homeostasis within the brain.They are implicated in the pathogenesis and progression of multiple central nervous system diseases.This review mainly focuses on the anatomical structure and physiological functions of meningeal lymphatic vessels,with brief introduction to their role in neurological diseases.We summarize recent research advances in meningeal lymphatic vessels,and provide insights for further research and clinical applications.

Objective To survey and analysis of cephalometric indicators of Wa adults in China.Methods Cephalometric parameters were measured in 1996 cases(858 males and 1138 females)of Wa adults in China,including 927 cases(381 males and 546 females)of the Baraoke ethnic group,564 cases(241 males and 323 females)of the A Wa ethnic group,and 505 cases(236 males and 269 females)of the Wa ethnic group by using sliding caliper and spreading caliper.Seventeen direct cephalofacial parameters and one indirect parameter for each of the three dialect ethnic groups were derived separately and analyzed for age correlations,inter-sex u-tests,and multiple comparisons.Finally,the three dialect ethnic groups were subjected to cluster analysis and principal component analysis with 15 ethnic groups in China.Results Nose breadth,mouth breadth and physiognomic ear length were significantly and positively correlated with age for both sexes in the three Wa dialect ethnic groups,while head breadth and lip height were significantly and negatively correlated with age.Except for the interocular breadth,there were gender differences between males and females in the cephalometric parameters of the three Wa dialect ethnic groups.The cephalofacial features of the Baraoke,A Wa and Wa ethnic groups were different,as evidenced by the fact that males and females of the Baraoke and Wa dialect ethnic group had higher lip height,wider nasal breadth and wider mouth breadth,while males and females of the A Wa ethnic group had lower nasal height.Conclusion The cephalofacial features of the three Wa dialect ethnic groups are close to those of the Khmus and Mang,who have their origins in the ancient Baipu people and are also members of the Mon-Khmer language group of the Austroasiatic linguistic.

Human beings are inevitably exposed to toxic substances as a result of influences of potential contamination factors in the environment,food and medicines,which poses a threat to human health.In order to effectively screen and prevent the exposure or intake of such substances,it is neces-sary to develop in vitro assays for the detection and toxicity evaluation of toxic substances.High content screening(HCS)has been recognized as an important tool for toxicity testing and risk assessment of compounds due to its high throughput and automation advantages,and has been widely used in in vitro toxicology research.In this review,we described the system components of HCS and its workflow in toxicity screening and toxicity evaluation by focusing on cases of their application in toxicity detection and evaluation studies,including the cytotoxicity,hepatotoxicity,nephrotoxicity,genotoxicity,neurotox-icity,cardiotoxicity,and developmental toxicity.In addition,the applications and developments of machine learning in HCS were explored,especially to the advantages of supervised and unsupervised machine learning strategies for high throughput image screening and data analysis.Finally,the future applications of HCS in toxicity screening and evaluation are outlined,especially in terms of binding new models and gene editing technology.

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.

Objective:To investigate the efficacy and safety of ixazomib combined with thalidomide and dexamethasone in the treatment of multiple myeloma(MM).Methods:The clinical data of 60 MM patients admitted to our center from January 2019 to June 2022 were analyzed retrospectively,including 43 newly diagnosed patients and 17 patients with recurrence and progression.All patients were treated with ixazomib combined with thalidomide and dexamethasone,and completed 2 to 7 treatment cycles.Results:The overall response rate(ORR)of all patients was 98.3％.Among them,53 patients completed 4 treatment cycles,and the ORR was 86.8％.Seventeen patients completed the whole treatment cycle,with curative effect reaching 88.2％achieving very good partial response and above,and 52.9％achieving complete response and above.Albumin and β2-microglobulin of all patients had been improved rapidly after treatment.The deadline was August 31,2022.The median follow-up time was 14(3-24)months,and overall survival(OS)rate was 86.67％.The OS rate of patients with recurrence and progression was significantly lower than that of newly diagnosed patients(P＜0.05).The most common adverse reaction of hematology was lymphopenia(53.3％),followed by anemia(33.3％).The most common non-hematological adverse reaction was fatigue(68.33％),followed by peripheral neuropathy(31.67％).Conclusion:Ixazomib combined with thalidomide and dexamethasone is effective in the treatment of MM,with good short-term efficacy,survival and safety.However,its long-term efficacy needs further observation.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.