Objective To screen and analyze the influencing factors of severity in the patients with type 2 diabetes mellitus (T2DM) complicating cerebral small vessel disease (CSVD).Methods A total of 519 pa-tients with T2DM complicating CSVD admitted and treated in Nanjing Municipal Hospital of Traditional Chi-nese Medicine from June 2018 to May 2023 were selected and divided into the mild group (n=214) and the se-vere group (n=305) according to the CSVD imageological score.The relevant demographic,laboratory and imageological indicators were collected.The influencing factors of T2DM complicating CSVD were screened out by the LASSO and Logistic regression analysis and the predictive model was established.The receiver op-erating characteristic (ROC) curve,goodness of fit evaluation and restricted cubic spline (RCS) fitting curve were drawn to analyze the dose-response relationship between Cys C,albumin/globulin (A/G) ratio with the disease severity.Results The male proportion and age in the severe group were greater than those in the mild group,neutrophil,systemic immune-inflammation index (SII),creatinine (Crea),uric acid (UA),Urea (Ure-a),D-dimer (D-D),lactate dehydrogenase (LDH),adenosine deaminase (ADA),globulin (GLB) and Cys C were higher than those in the mild group,lymphocyte,ALT,High density Lipoprotein-cholesterol (HDL-C),serum cholinesterase (CHE),prealbumin (PAB),and A/G were lower than those in the mild group,and the differences were statistically significant (P<0.05).LASSO and logistic regression analysis showed that the gender,age,A/G and Cys C were the independent influencing factors in the patients with T2DM complicating CSVD.The area under the curve (AUC) of this model was 0.658 (95%CI:0.610-0.706) with goodness of fit (P=0.520).The RCS fitting curves showed that serum Cys C≥0.618 mg/L had a linear relationship with CSVD imageological score (P=0.035),and A/G≥1.268 had a nonlinear relationship with CSVD imageologi-cal score (P=0.007).Conclusion The advanced age,male,increased Cys C level and decreased A/G in the pa-tients with T2DM complicating CSVD are the independent risk factors for the severity of whole brain damage.

Objective To screen the characteristic factors of renal impairment occurrence in the patients with hyperuricemia,and to analyze its diagnostic value and establish a diagnostic model.Methods A total of 2405 inpatients with diagnosed hyperuricemia in the Nanjing Municipal Hospital of Traditional Chinese Medi-cine,Nanjing University of Traditional Chinese Medicine from December 2018 to December 2022 were selected and divided into the kidney lesion group (n=1343) and the non-kidney lesion group (n=1062) according to eGFR.The characteristic factors of hyperuricemia caused renal impairment were screened and analyzed by Lasso and logistic regression and the diagnostic model was constructed.The diagnostic value of characteristic factors and diagnostic model were evaluated by the receiver operating characteristic (ROC) curve,and the change rule between the characteristic factors and the results was found by the restricted cubic splines (RCS) fitting.Results The age,uric acid (UA),cystatin-C (Cys-C) and retinol-binding protein (RBP) were the characteristic factors of hyperuricemia caused renal impairment.The combined diagnostic model:logit (P)=-8.70+0.602×age (10 years old)+0.033×UA (10 μmol/L)+0.277×Cys-C (0.1 mg/L)+0.189×RBP (10 mg/L),the area under the ROC curve (AUC) of the combined diagnosis model was 0.893 (95％CI:0.880-0.905).For every 10 μmol/L increase in blood UA,the risk of renal impairment occurrence in hyperurice-mia was increased by 3％;for every 10 years increase in age,the risk of renal impairment occurrence in hyperu-ricemia was increased by 83％;for every 10 mg/L increase in RBP,the risk of kidney damage occurrence of re-nal impairment in hyperuricemia was increased by 21％;for every 0.1 mg/L increase in Cys-C,the risk of re-nal impairment occurrence in hyperuricemia was increased by 32％.Conclusion The combined diagnostic model for whether the renal impairment in the patients with hyperuricemia occurring has good diagnostic val-ue,and Cys-C deserves more attention.

AIM:To study the effect of hepatitis B combined with hepatic fibrosis on endogenous and exogenous metabolism of liver and the effect of glycyrrhizic acid combined with tenofovir(TFV)es-ter on anti-HBV efficacy.METHODS:Hepatitis B mouse was induced by chronic CCI4 to form a mod-el of hepatitis B with hepatic fibrosis.H&E staining,Sirius Red Staining,α-SMA immunohistochemistry were used to detect pathological changes in liver tissue.The changes of liver endogenous metabo-lism in mice with hepatitis B and hepatic fibrosis were detected by metabolomics.LC-MS/MS was used to investigate the plasma and liver concentra-tions of TFV and its active metabolite(TFV-DP),for investigating the changes of exogenous metabo-lism.RESULTS:HBV+CCl4 mice showed fibrosis symptoms such as liver injury and collagen deposi-tion.Hepatitis B combined with hepatic fibrosis af-fected nucleotide metabolism,amino acid metabo-lism,tricarboxylic acid cycle,pentose phosphate pathway and other endogenous metabolism,low-ered the hepatic level of TFV-DP,and decreased the antiviral efficacy.By combining with glycyrrhizic acid or forming a self-assembled preparation,the hepatic level of TFV-DP was improved,and the anti-viral efficacy was enhanced.CONCLUSIONS:Hepati-tis B combined with hepatic fibrosis affected both endogenous and exogenous metabolism of liver.Different forms of combination of glycyrrhizic acid and TFV could elevate the level of TFV-DP in liver and improve the antiviral efficacy in HBV+CCI4 mice.

Objective:To evaluate the clinical value of the adjusted global antiphospholipid syndrome score (aGAPSS) in patients with persistent antiphospholipid antibodies (aPL).Methods:The clinical data of patients who were continuously positive for aPL from May 2012 to August 2022 were retrospectively analyzed, except for patients complicated with connective tissue diseases. Demographic data, traditional cardiovascular thrombosis risk factors, aPL profile, and clinical manifestations included and not included in antiphospholipid syndrome (APS) were collected, and aGAPSS was calculated for all patients according to risk indicators and the correlation with clinical manifestation was analyzed through rank sum test. The diagnostic value of aGAPSS for different clinical manifestations was evaluated by the receiver operator characteristic (ROC) curve.Results:A total of 67 patients with persistent aPL were enrolled, including 15 patients with persistent extra-criteria positive aPL but did not meet the APS classification criteria and 52 patients with a clear diagnosis of primary APS, of which 20 had a history of thrombosis, 36 had a history of pregnancy morbidity, and 24 had extra-criteria clinical manifestations. Patients with history of any thrombosis or arterial thrombosis scored significantly higher than those with no history of thrombosis [any history of thrombosis 11.50 (8.25, 13.00) vs 8.00 (4.00, 13.00), Z=2.33, P=0.020; arterial thrombosis history 11.00 (9.00, 14.00) vs 8.00 (4.00, 13.00), H=6.21, P=0.043]. The aGAPSS score of patients with extra-criteria clinical manifestations was significantly higher than that of patients without corresponding clinical manifestations [13.00 (8.25, 13.00) vs 8.00 (4.00, 11.00), Z=2.81, P=0.005], and the aGAPSS score of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia [12.50 (8.00, 13.25) vs 8.00 (4.00, 13.00), Z=2.23, P=0.026]. A subgroup analysis of pregnant women found no statistically significant difference in aGAPSS scores between groups with or without a history of pregnancy morbidity. With thrombosis as the endpoint event, aGAPSS had the highest diagnostic value at 10 points(sensitivity and specificity were 65.00% and 77.78%, respectively). Conclusion:In patients with postivity aPL positivity, aGAPSS score is correlated with thrombosis history and extra-criteria clinical manifestations, especially thrombocytopenia.

OBJECTIVE To analyze the effect of pharmaceutical practice of pediatric pharmacists providing internet medication consultation services. METHODS A total of 8 356 children’s medication cases through the “Our Pharmacists” online medication consultation platform （hereinafter referred to as “Our Pharmacists”） were collected from July 2020 to June 2022. The general information， disease type and irrational drug use were analyzed statistically. RESULTS Among 8 356 cases， 4 234 were male and 4 122 were female； the age of children was mainly from 12 months to 3 years old； the consulting diseases were mainly respiratory diseases （46.56%）， followed by digestive system diseases （18.41%） and skin system diseases （12.71%）. Among respiratory diseases， the proportion of irrational drug use was 92.30%， mainly including the use of antibiotics without indication （83.59%）， inappropriate selection of Chinese patent medicines （61.14%） and compound cold medicines （49.77%）， etc. Among digestive system diseases， the proportion of irrational drug use was 71.15%， mainly including not using oral rehydration salts （48.85%）， inappropriate use of probiotics （31.19%）， the use of antibiotics without indication （26.89%）， etc. A total of 4 273 evaluations of pharmacist services were received from child guardians， with a five-star rating of 99.88%. CONCLUSIONS Pharmacists provide pediatric medication consultation services through “Our Pharmacists”， providing individualized evidence-based medication suggestions， increasing the safety of drug use and satisfaction with pharmaceutical care， and ensuring the safety of children medication.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective:To investigate the therapeutic value of modified multipoint drainage for biliary complications after liver transplantation.Methods:A total of 125 patients treated by endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications after liver transplantation in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2018 to May 2020 were enrolled. Patients were divided into endoscopic retrograde biliary drainage (ERBD) group ( n=67, treated with multiple drainage of bile duct stent) and modified multipoint drainage group [ n=58, treated with ERBD combined with endoscopic nasobiliary drainage (ENBD)] by random number table. Modified multipoint drainage group were further randomly divided into two groups, modification group 1, 31 cases, where nasobiliary ducts were cut proximal to duodenal papilla after one week under endoscopy and modification group 2, 27 cases, where they were cut proximal to duodenal papilla after two weeks under endoscopy. The changes of serological indexes in 2 weeks after the operation in three groups were compared, and the incidence of short-term and long-term complications were analyzed. Results:The serological indexes were improved in patients at 1 d, 7 d and 14 d after ERCP, especially in modified multipoint drainage groups. Two weeks after the operation, the improvement of serological indexes in modification group 2 was better than that in modification group 1. Incidence of recent complications including cholangitis, hyperamylasinemia, and pancreatitis in the ERBD group were higher than those in modification group 1 [32.84% (22/67) VS 12.90% (4/31), 46.27% (31/67) VS 19.35% (6/31), 20.90% (14/67) VS 3.23% (1/31), all P<0.05] and modification group 2 [32.84% (22/67) VS 11.11% (3/27), 46.27% (31/67) VS 22.22% (6/27), 20.90% (14/67) VS 3.70% (1/27), all P<0.05]. ERBD group had a higher incidence of long-term complications including recurrent biliary infection and jaundice than modification group 1 [ 58.21% (39/67) VS 35.48% (11/31), P=0.036; 49.25% (33/67) VS 25.81% (8/31), P=0.027] and modification group 2 [58.21% (39/67) VS 11.11% (3/27), P<0.001; 49.25% (33/67) VS 25.93% (7/27), P=0.038]. The incidence of recurrent biliary infection in modification group 1 was higher than that in modification group 2 [35.48% (11/31) VS 11.11% (3/27), P=0.030]. Conclusion:Multiple drainage with indwelling nasal bile duct by ERCP can effectively reduce the short-term and long-term complications and improve the recovery of serological indexes for patients with biliary complications after liver transplantation. It is suggested that the nasobiliary duct should be retained for 2 weeks and then transformed into a built-in tube to continue drainage.

OBJECTIVE To investigate the pharmacological components and mechanism of Qingre huoxue decoction in improving myocardial ischemia-reperfusion injury（MIRI）. METHODS Forty-two rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， Qingre huoxue decoction low-dose， medium-dose and high-dose groups （4.94， 9.88， 19.79 g/kg），Qingre huoxue decoction drug-containing serum group （19.79 g/kg） and blank serum group （normal saline）， with 6 rats in each group. Each group was given corresponding drug/normal saline intragastrically， once a day， for consecutive 2 weeks. Twelve hours after last administration， except for serum groups， MIRI model was induced in other groups （only threading without ligation in sham operation group）. After modeling， cardiac histopathology was observed and apoptosis level was detected. UPLC-MS was used to analyze the samples in Qingre huoxue decoction drug-containing serum group and blank serum group. The main pharmacological components were screened with the help of relevant databases. Multivariate statistical methods were used to analyze the differential metabolites and related metabolic pathways. Validation test was performed based on oxidative stress indicators. RESULTS Qingre huoxue decoction could improve the pathological injury of cardiac tissue and decrease apoptosis rate of cardiac cells in MIRI model rats （P＜0.05）. Qingre huoxue decoction drug-containing serum contained 20 main pharmacological components such as baicalin， succinic acid， baicalein， cryptotanshinone， isoferulic acid， protocatechuic aldehyde. Qingre huoxue decoction could significantly up-regulate the levels of 15 metabolites including L-arginine， L-arginine， citric acid， glutathione， β-D- glucose and L-carnitine， and down-regulated the levels of 14 metabolites including arachidonic acid， 3-phosphate-d-glycerol phosphate， linoleic acid， docosahexaenoic acid， phosphatidylcholine and lysophosphatidylcholine （P＜0.05）. These metabolites were mainly involved in energy metabolism， inflammatory injury， oxidative stress and autophagy. Results of validation tests showed that Qingre huoxue decoction could significantly reduce the levels of malondialdehyde， and increased the levels of superoxide dismutase （except for low-dose group） and glutathione peroxidase significantly （P＜0.05）. CONCLUSIONS Qingre huoxue decoction can improve the injury of cardiac tissue in MIRI model rats. Its pharmacological components include baicalin， cryptotanshinone， isoferulic acid， protocatechualdehyde， etc. Furthermore， it may play a protective role in MIRI by improving myocardial energy metabolism， down-regulating oxidative stress， inhibiting inflammation infiltration.

Objective:To investigate the effect of a 2-year resistance and aerobic training on reducing the risk of cardiovascular disease in patients with prediabetes.Methods:A total of 248 patients with prediabetes were enrolled from Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from January to April 2014, and Danyang People′s Hospital and The First Affiliated Hospital of Guangxi Medical University from May to December 2014.Based on random number table method, the patients were divided into 3 groups: the resistance training group (RT group, 82 cases), the aerobic training group (AT group, 83 cases) and control group (83 cases). Participants in the RT group and the AT group underwent a total of 24 months of exercise training. Changes in indicators (blood glucose,blood lipid, etc.) at baseline and the end of 12 and 24 months among the groups were compared.Results:After intervention, glycosylated hemoglobin (HbA1c), low density lipoprotein cholesterol (LDL-C), blood pressure and homeostasis model 2 insulin resistance index (HOMA2-IR) in the RT and AT groups tended to decrease, and the steady state model 2 β cell function index (HOMA2-β) tended to increase. At the end of 24 months, HbA1c [5.80 (5.43, 6.20) %, 5.70 (5.50, 6.00)% vs. 6.20 (5.70, 6.60) %, all P≤ 0.01], LDL-C [3.07 (2.69, 3.58) mmol/L, 2.97 (2.62, 3.95) mmol/L vs. 3.21(2.54, 3.78) mmol/L, all P<0.05] and HOMA2-IR [0.96 (0.82, 1.47), 1.20 (0.99, 1.43) vs. 1.34 (1.09, 1.51), all P<0.05] were significantly decreased in the RT and AT groups than in the control group. In addition, HOMA2-β [84.50 (60.55, 107.33), 93.00 (78.60, 119.75) vs. 53.40 (37.70, 80.40), all P = 0.001] was significantly increased in the AT and RT groups compared with that in the control group. There were no significant differences in triglyceride (TG) and high-density lipoproteincholesterol (HDL-C) levels between the training groups and the control group (all P>0.05). After adjusting for age, sex and blood pressure, the cardiovascular risk of prediabetes was significantly reduced in RT ( P =0.017) and AT groups ( P =0.018). The Cox regression analyses showed that both the resistance training (HR=0.419, 95 %CI =0.415-0.942, P=0.037) and the aerobic training ( HR=0.310, 95 %CI=0.447-0.866, P=0.026) were protective factors for cardiovascular disease in prediabetic patients after adjustment of age, sex, statins, body mass index and waist-to-hip ratio, which reduced the risks of cardiovascular disease in prediabetic patients by 58.1% and 69.0%, respectively. Conclusions:Two years of aerobic and resistance training interventions have obvious advantages on glycemic and insulin resistance control in prediabetes patients. The resistance training can reduce the risk of cardiovascular disease, and it is, thus, recommended for prediabetic patients without obvious exercise contraindications.

Objective:To evaluate the impacts of resistance training(RT)and aerobic training(AT)for 24 months on the risk of type 2 diabetes in patients with pre-diabetes.Methods:Two hundred forty-eight pre-diabetic patients were enrolled in this multi-center randomized controlled trial. All patients were randomly divided into 3 groups: RT( n=82), AT( n=83), and control( n=83)groups. The participants in RT and AT groups undertook moderate RT or AT 3 times a week(150 minutes/week)under supervision in 3 research centers for 24 months. Elastic bands were used in each session of RT, with intensity of 60% 1RM(maximum weight that muscle can lift at once). Patients in AT group performed aerobic dance at 60%-70% of maximum heart rate. Assessments for each subject were made at baseline and by the end of 6, 12 and 24 months. Primary outcomes were changes in the risk of type 2 diabetes. Secondary outcomes included changes in blood glucose, blood lipids, and blood pressure. Results:There were 217, 206, and 173 subjects who completed the follow-up of 6, 12, and 24 months, respectively. The mean ages of RT, AT, and control groups at baseline were(59.91±5.92), (60.93±5.71), and(60.73±5.83)years. Compared to control group, both RT and AT groups revealed a significant reduction in HbA 1C( P<0.05), and a significant increase in homeostasis model assessment for β-cell function index(HOMA2-β, P<0.01)by the end of 12 and 24 months. Adjusted for age, gender, statin use, lipid profile, blood pressure, and body mass index, COX regression analysis showed that RT and AT reduced the risk of type 2 diabetes by 55.6%( P=0.012)and 59.8%( P=0.010). Conclusions:This study demonstrates that 24-month moderate RT and AT have comparable effects on reducing insulin resistance, improving β-cell function, blood glucose and lipid, and reducing the risk of type 2 diabetes.