ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the mechanism of curcumin in the treatment of diabetic retinopathy (DR) by network pharmacology and molecular docking.Methods:The compounds targets of curcumin were predicted by SEA and SwissTargetPrediction databases, and the DR target genes were obtained by CTD database.The different genes were mapped and matched by Venny database to screen their intersections.The intersecting genes were submitted to GeneMANIA database to construct a protein-protein interaction network.WebGestalt database was used to conduct enrichment analysis and AutoDock Vina was used to perform molecular docking of the core targets.Results:A total of 52 targets of curcumin, 1 599 targets of DR and 48 intersecting targets were detected.The core targets were serine/threonine-protein kinase 1 (AKT1), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR), signal transduction and activator of transcription 3 (STAT3) and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Enrichment analysis suggested that these targets were mainly associated with signaling pathways, including the EGFR tyrosine kinase inhibitor resistance signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway and advanced glycosylation end product-the receptor of advanced glycosylation end product (AGE-RAGE) signaling pathway.Conclusions:Curcumin may play an important role in the treatment of DR by regulating multiple signaling pathways to inhibit the inflammatory response and combat oxidative stress.

A case of syphilis-related membranous proliferative glomerulonephritis is reported, presenting with fever, rash, generalized lymphadenopathy, and peripheral hypocytosis as the initial symptoms. The patient was admitted to the hospital and underwent various examinations to rule out lymphoma and other diseases. Subsequently, the patient developed edema with proteinuria. The toluidine red unheated serum test (TRUST) was 1∶4 (+) and the treponema pallidum particle agglutination (TPPA) test was >1∶160 (+). The pathological results of renal biopsy revealed membranous proliferative glomerulonephritis. The diagnosis of the patient was considered syphilitic nephropathy. Treatment with penicillin resulted in improvement of the condition. The coexistence of syphilitic nephropathy and membranous proliferative glomerulonephritis is rare and should be given careful attention in clinical practice. Antisyphilitic treatment improves the prognosis.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

Objective To explore the impact of arterial injury on distal limb blood supply in lower limb trauma. Meth?ods Retrospective analysis of 93 patients with different levels of lower limb arterial injury admitted to our hospital from June 2014 to August 2017. There were 84 males and 9 females aged 43.54±9.90 years (ranging 25-65 years). Revascularization was performed through open reduction. Patients were divided into three groups according to their arterial injury locations. Proximal ves?sels were along the superficial femoral artery, from its beginning to the point where it was divided into the descending genicular ar?tery and direct periosteal branches. Intermediate vessels were from the dividing point on the superficial femoral artery to the popli?teal artery before it was divided into the medial inferior genicular artery. Distal vessels were from the dividing point on the poplite?al artery to the distal end of the peroneal artery. The duration from injury to revascularization in the three groups were 13.67±5.99 h, 11.15±4.43 h, and 11.92±5.48 h, respectively. There was no significant difference between groups (F=1.564, P=0.215). ISS in the three groups were 13.00±3.74, 12.77±3.81, and 11.50±3.99, respectively. There was no significant difference between groups (F=1.445, P=0.241). The following items were compared among the three groups, postoperative creatine kinase, arterial blood lac?tate and limb compartment cut. Results Creatine kinase of the intermediate vascular group was 8 743.15±6 968.48 u/L, proximal vascular group 1 467.67±1 810.27 u/L, distal vascular group 2 893.51±1 304.56 u/L. The data of intermediate vascular group were higher than those of proximal and distal vascular groups with significant difference among the groups (F=22.587,P=0.000). The lactate of the intermediate vascular group was 3.20 ± 1.51 mmol/L, proximal vascular group 1.63 ± 0.46 mmol/L, distal vascular group 1.85±0.69 mmol/L with significant difference among the groups (F=20.612,P=0.000). The compartment cut of the intermedi?ate vascular group was incised in 24, but not in 15. The proximal vascular group was not incised in 18, while 15 was incised and 21 not incised in distal vascular group. The rates of compartment cut were 61.5%, 0 and 41.7%, respectively with significant differ? ences (χ2=19.156, P=0.000). Conclusion In lower limb injuries, the intermediate vascular (from the superficial femoral artery after it is divided into the descending genicular artery and direct periosteal branches to the popliteal artery before it is divided into the medial inferior genicular artery) injury leads to the most severe distal limb ischemia.

Objective: To explore the blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing. Methods: A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q₁-Q₄ groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results: The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) μg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q₁ group, the OR (95%CI) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q₃ group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI) value of high long term memory (LTM) scores in Q₄ group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose-response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion The blood lead level of school-age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long-term memory ability.

OBJECTIVE： To systematically evaluate effectiveness and safety of single antiplatelet therapy （SAPT） versus dual antiplatelet therapy （DAPT） on short-term complications after transcatheter aortic valve implantation （TAVI）， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Cochrane clinical controlled trials registry， Web of Science， CNKI， Wanfang database， CBM and Chinese Clinical Trial Registry， RCTs and observational studies about effectiveness （all-cause mortality， incidence of stroke and incidence of myocardial infarction 30 days after operation） and safety （the incidence of bleeding events at 30 days after operation） of SAPT versus DAPT on short-term complications of TAVI were collected during the date of database establishment to Jan. 2019. After data extraction of included studies and quality evaluation with Cochrane system evaluator manual 5.1.0 （for RCT） and the Newcastle-Ottawa Scale （NOS） （for observational studies）， Meta-analysis was conducted by using Rev Man 5.3 statistical software. RESULTS： Totally 3 RCTs and 7 cohort studies were included， involving 3 188 patients. Results of Meta-analysis showed that the incidence of all-cause mortality 30 days after operation [OR＝0.48， 95％ CI （0.32， 0.73）， P＜0.001] and the incidence of bleeding events 30 days after operation [OR＝0.43， 95％CI （0.30， 0.59）， P＜0.001] in SAPT group were significantly lower than DAPT group， with statistical significance. There was no statistical significance in the incidence of stroke 30 days after operation [OR＝0.63， 95％CI （0.38， 1.06） ， P＝0.08] or the incidence of myocardial infarction 30 days after operation [OR＝1.09， 95％CI （0.46， 2.59）， P＝0.85] between 2 groups. CONCLUSIONS： Compared with DAPT， SAPT can decrease the incidence of all-cause mortality 30 days after TAVI and the incidence of bleeding events 30 days after TAVI.

Objective To explore the blood lead level and its relationship with behavior in school?age children from rural areas of Chongqing. Methods A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q1-Q4 groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) μg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q1 group, the OR (95%CI ) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q 3 group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI ) value of high long term memory (LTM) scores in Q4 group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose?response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion The blood lead level of school?age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long?term memory ability.