OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

[Objective] To investigate the factors associated with alanine aminotransferase (ALT) abnormalities in multi-ethnic blood donors across five Zang autonomous prefectures in the plateau regions of Qinghai Province, and to provide evidence for ensuring blood safety and formulating screening strategies. [Methods] A retrospective analysis was performed on the ALT abnormal test results of blood donors in the Zang autonomous prefectures of Qinghai from 2022 to 2024. The correlations between ALT levels and factors including gender, age, altitude, and infectious markers were investigated. [Results] The overall ALT unqualified rate among blood donors in this region was 9.01%. Significant differences in ALT levels were observed across genders and age groups (P<0.05). Variations in ALT abnormality rates were also noted among different plateau regions (P<0.05). Overall, ALT values exhibited an increasing trend with rising altitude. The average ALT unqualified rates were 11.19% in Zang donors, 7.96% in Han donors, and 4.79% in donors from other ethnic groups (P<0.05). No statistically significant association was observed between ALT abnormality and the presence of HBV/HCV infectious markers (P>0.05). [Conclusion] In the plateau areas of Qinghai, multi-ethnic blood donors have a relatively high ALT levels and ALT unqualified rates, showing distinct regional characteristics. ALT elevation in voluntary blood donors is related to non-pathological factors such as gender, age, and dietary habits, but not to infectious indicators.

Objective To investigate the effects of long non-coding RNA (LncRNA) solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1) targeting microRNA-615-5p (miR-615-5p) in esophageal cancer cells on cell proliferation, apoptosis, and expression of inflammatory factors. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression of LncRNA SLCO4A1-AS1 and miR-615-5p in esophageal cancer tissues and cell lines. Eca109 cells were transfected with si-NC, si-LncRNA SLCO4A1-AS1, miR-NC, miR-615-5p mimic, pcDNA, pcDNA-LncRNA SLCO4A1-AS1, si-LncRNA SLCO4A1-AS1+anti-miR-NC, and si-LncRNA SLCO4A1-AS1+anti-miR-615-5p. Cell viability and apoptosis rate were measured by CCK-8 and flow cytometry, respectively; cell proliferation was determined by plate cloning assay; and levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the culture medium were measured using an enzyme-linked immunosorbent assay (ELISA) kit. A dual luciferase reporter gene assay was used to determine the relationship between LncRNA SLCO4A1-AS1 and miR-615-5p. Results Expression of LncRNA SLCO4A1-AS1 was upregulated, and miR-615-5p expression was downregulated in esophageal cancer tissues and cell lines. After inhibiting LncRNA SLCO4A1-AS1 expression, cell viability, the number of cell clones, and levels of IL-6 and TNF-α in the culture medium decreased, while miR-615-5p expression and apoptosis rate increased (P < 0.05). Compared with the miR-NC group, the miR-615-5p group showed increased miR-615-5p expression, levels of Cleaved-caspase-3 protein, and apoptosis rate, and decreased cell viability, the number of cell clones, and levels of IL-6 and TNF-α in the culture medium (P < 0.05). Compared with the si-LncRNA SLCO4A1-AS1+anti-miR-NC group, the si-LncRNA SLCO4A1-AS1+anti-miR-615-5p group showed decreased miR-615-5p expression, levels of Cleaved-caspase-3 protein, and apoptosis rate, and increased cell viability, the number of cell clones, and levels of IL-6 and TNF-α in the culture medium (P < 0.05). Conclusion LncRNA SLCO4A1-AS1 can promote the occurrence and development of esophageal cancer. Inhibiting LncRNA SLCO4A1-AS1 can reduce the proliferation of esophageal cancer cells, decrease the expression of inflammatory factors, and induce apoptosis.

Objective:To analyze the application and regularity of acupoint selection of Sanyinjiao (SP 6) based on data mining.Methods:Search for literatures in CNKI, Wanfang, VIP, and Pubmed, the clinical researches of acupuncture on Sanyinjiao (SP 6) point were selected, according to the inclusion and exclusion criteria, and the retrieval period was from database construction to September 30th, 2021. Excel 2016, SPSS Statistics 25.0, SPSS Modeler 18.0 were used to perform descriptive analysis, association analysis and cluster analysis.Results:After literature screening, a total of 261 literatures were included, involving 73 kinds of diseases, mainly including mental and behavioral disorders, genitourinary diseases, endocrine and nutritional metabolism diseases and nervous system diseases. The most frequently used acupoints in Sanyinjiao (SP 6) compatibility are Zusanli (ST 36), Baihui (GV 20), Guanyuan (CV 4) and Taichong (LR 3), most of which focus on stomach meridian, conception channel, governor channel and bladder meridian. Seven categories were extracted among high-frequency acupoints by cluster analysis. The association rule analysis showed that the commonly used combination of Sanyinjiao (SP 6) were Zusanli (ST 36)-Sanyinjiao (SP 6), Baihui (GV 20)-Sanyinjiao (SP 6), and Guanyuan (CV 4)-Sanyinjiao (SP 6).Conclusions:Sanyinjiao (SP 6) is widely used in clinical application, and it is always compatible with stomach meridian, conception vessel, governor channel acupoints, especially those acupoints on the outer and inner meridians and the upper and lower parts. Sanyinjiao (SP 6) combined with other acupoints can treat diseases of multiple systems, such as insomnia, stroke, anxiety and depression, dysmenorrhea, infertility, etc. Clustering and association analysis found the core compatibility law of Sanyinjiao (SP 6), which can be used as a reference for clinical acupoint selection.

Abstract To study the antiviral effect ofZedoary TurmericOil Injection on novel coronavirus, SARS-CoV-2 viroid cell lines were preparedin vitroand treated with different concentrations of Zedoary Oil. The cell number and relative fluorescence value(RLU) were observed and measured, and the 50% effective inhibitory concentration(IC 50) was calculated. Four patients with Coronavirus Disease 2019 were clinically included, including 2 in the control group and 2 in the experimental group. The control group received conventional treatment, and the experimental group receivedZedoary TurmericOil Injection in addition to conventional treatment. The nucleic acid conversion rate, conversion time, pulmonary imaging changes, fever reduction time, clinical improvement time and adverse events of the patients were observed.In vitroexperiment, the relative fluorescence value decreased with increasing concentration ofZedoary TurmericOil, which was significantly different from that of the control group(P<0.05). The IC50 was 0.26 μg/ml.In vivostudy, the novel coronavirus nucleic acid in stool of case 1 in the test group turned negative in 3 days, the cough symptom of case 2 was significantly relieved, and there was obvious absorption in pulmonary imaging. The negative conversion time of novel coronavirus nucleic acid in the control group was 5 and 7 days respectively. No adverse events occurred in the experimental group.Zedoary TurmericOil had strong inhibitory effect on SARS-COV-2 virusin vitrowhich was dose-dependent.In vivotreatment of COVID-19,Zedoary TurmericOil Injection combined with conventional treatment can improve the cough caused by SARS-COV-2 infection, promote SARS-COV-2 to turn negative, promote absorption of lung lesions, and reduce lung injury, with no obvious adverse events.

Objective To analyze the risk factors for the occurrence of post transplantation diabetes mellitus (PTDM) in renal transplant recipients, establish a prediction model for PTDM and evaluate its prediction value. Methods Clinical data of 915 renal transplant recipients were retrospectively analyzed. According to the occurrence of PTDM, all recipients were divided into the PTDM group (n=78) and non-PTDM group (n=837). The main indexes of recipients were collected. The risk factors for the occurrence of PTDM in renal transplant recipients were analyzed by univariate and multivariate analysis. The prediction model for PTDM was established and its prediction value was evaluated. Results Family history of diabetes mellitus, body mass index (BMI), preoperative 2 h postprandial blood glucose and preoperative glycosylated hemoglobin were the independent risk factors for the occurrence of PTDM in renal transplant recipients. The prediction model for PTDM was logit (P)=2.199×family history of diabetes (yes=1, no=0)+0.109×BMI+0.151×2 h postprandial blood glucose (mmol/L)+0.508×glycosylated hemoglobin (%)-9.123. The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of these 4 predictors combined for predicting PTDM in renal transplant recipients was 0.830 [95% confidence interval (CI) 0.786-0.873], the cut-off value was 0.0608, the sensitivity was 0.821, the specificity was 0.700, and the Youden index was 0.521 (P < 0.05). Conclusions Family history of diabetes mellitus, BMI, preoperative 2 h postprandial blood glucose and preoperative glycosylated hemoglobin are the independent risk factors for the occurrence of PTDM in renal transplant recipients. The prediction model for PTDM combined with4 predictors yield relatively high prediction value for PTDM.

Objective:To investigate the effects and mechanisms of allogeneic epidermal stem cells (ESCs) on the survival of allogeneic full-thickness skin grafts in nude mice with full-thickness skin defect wounds.Methods:Experimental research methods were applied. Primary ESCs that appeared paving stone-like after being cultured for 7 d were obtained by enzymatic digestion method from one 4-week-old male BALB/c-NU nude mouse (the same strain, age, and sex below). The cells of third passage were identified by flow cytometry to positively express ESC marker CD44 and negatively express CD45, meanwhile, the positive expression of ESC markers of p63 and integrin 6α, and negative expression of CD71 were identified by immunofluorescence method. The ESCs of third passage in the logarithmic growth phase were used for the following experiments. Twenty-six nude mice were equally divided into phosphate buffered saline (PBS) group and ESCs group according to the random number table. A full-thickness skin defect wound was made on the back of each nude mouse, and then the wounds of the two groups were sprayed with equal volumes of PBS and ESCs, respectively. The wounds were transplanted with full-thickness skin grafts cut from the backs of 4 other nude mice. Each ten nude mice from the two groups were selected, the wound healing and skin survival on post surgery day (PSD) 0 (immediately), 3, 7, 14, and 21 were observed, and the survival ratio and shrinkage rate of skin grafts on PSD 3, 7, 14, and 21 were calculated (the number of sample was the number of surviving skin grafts at each time point); the blood perfusion in the skin grafts on PSD 3, 7, and 14 was detected by the laser speckle blood flow imager, and the blood flow ratio of nude mice skin grafts in ESCs group to PBS group at each time point was calculated (the number of sample was the pair number of surviving skin grafts in group pairing at each time point). The skin graft tissue of each 3 nude mice remained in the two groups were collected on PSD 7, and the mRNA expressions and protein expressions of tumor necrosis factor α (TNF-α), interleukin 8 (IL-8), IL-10, type Ⅰ collagen, type Ⅲ collagen, and matrix metalloproteinase 9 (MMP-9) in the tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Data were statistically analyzed with Log-rank test, analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and Bonferroni correction. Results:Taking the condition on PSD 0 as a reference, the wounds of nude mice in the two groups healed gradually on PSD 3, 7, 14, and 21, and the shrinkage of skin grafts was gradually obvious. Among them, the shrinkage healing of wound of nude mice in PBS group was more significant than that in ESCs group. On PSD 3, the skin graft of 1 nude mouse failed in ESCs group, while the skin graft of 3 nude mice failed in PBS group. On PSD 7, the skin graft of another nude mouse failed in PBS group. The survival ratio of skin grafts of nude mice in the two groups was similar on PSD 3, 7, 14, and 21 ( P>0.05). On PSD 3, 7, 14, and 21, the shrinkage rates of skin grafts of nude mice in ESCs group were (9.2±0.4)%, (19.7±1.2)%, (53.6±3.5)%, and (62.2±5.1)%, respectively, which was significantly lower than (11.0±0.9)%, (47.8±2.8)%, (86.1±7.1)%, and (89.7±9.0)% in PBS group ( t=5.719, 26.650, 11.940, 7.617, P<0.01). On PSD 3, 7, and 14, blood perfusion signals were observed in the skin grafts of nude mice in the two groups. The average blood perfusion ratios of the skin grafts of nude mice in ESCs group to PBS group were greater than 1, and there was no statistically significant difference in the overall comparison of 3 time points ( P>0.05). On PSD 7, compared with those of PBS group, the mRNA and protein expressions of TNF-α, IL-8, type Ⅰ collagen, and type Ⅲ collagen in the skin graft tissue of nude mice in ESCs group were significantly reduced, while the mRNA and protein expressions of IL-10 and MMP-9 in the skin graft tissue of nude mice in ESCs group were significantly increased (in mRNA comparison, t=2.823, 2.934, 2.845, 2.860, 3.877, 2.916, P<0.05). Conclusions:Allogeneic ESCs can reduce the shrinkage of allogeneic full-thickness skin grafts transplanted on full-thickness skin defect wounds in nude mice, promote the formation of new blood vessels between the skin graft and the wound, reduce inflammation and collagen protein expression, and promote the expression of MMP-9, thus improving the survival quality of skin grafts.

Objective:To explore the clinical effects in repairing dorsal complex tissue defect of finger with the flap based on superficial palmar branch of radial artery (SPBRA) with palmaris longus tendon.Methods:From May, 2011 to October, 2017, dorsal complex tissue defects of 15 fingers and thumbs in 15 patients were treated by the flaps which were based on SPBRA with palmaris longus tendon. There were 10 males and 5 females, in an average of 35.8 (19-51) years. All the defects (3 thumbs, 5 index, 2 middle and 5 ring fingers) were dorsal complex tissue defects and all had extensor tendon defects. The areas of soft tissue defect measured 2.0 cm×1.5 cm to 4.0 cm×2.0 cm. The lengths of tendon defect measured 2.0-4.0 cm. All patients received emergency surgery. The time before the surgery was 1.5-3.0 hours. The surgery time was 3.0-4.5 hours, 3.6 hours in an average. Postoperative regular follow-up.Results:All of the wounds healed in stage I and all flaps survived. Texture of the flaps was soft with rosy color. No obvious swelling occurred. All the donor sites healed in stage I. The patients were followed-up for 4-18 months, 8 months in an average. The appearance and function of the repaired fingers and thumbs were satisfactory. The pain, temperature and touch sensations were good. The color of flaps was similar to the normal finger without swelling. The wear resistance of the flaps was good. Thin-line scars were in the wrist donor sites without contracture. The range of motion of active palmar flexion of the wrist was from 0° to 80° and active hyperextension was from 0° to 70°. No obvious limitation was found.Conclusion:It is able to achieve a satisfactory clinical effects by using the flap that is based on SPBRA with palmaris longus tendon in repairing the dorsal complex tissue defect of hand. The advantages of the technique are that the donor site is concealed. The wound is small, and the flap is easy to be harvested and anastomosed.

OBJECTIVE： To provide reference for the formulation of primary medication regimen for antibacterial drug treatment of ICU patients with Escherichia coli infection. METHODS： Based on the surveillance report on E. coli resistance in hospitals issued by CHINET China bacterial drug resistance surveillance network in 2016， 19 third class A hospitals in China were collected as E. coli clinically isolated from ICU wards. Antibiotics with resistance rate of less than 40％ to E. coli and with high utilization rate in clinical practice were selected as the research objects， and a simulated drug delivery scheme was formulated. Monte Carlo simulation method was used to simulate the clinical effect of different dosage regimens on 10 000 cases among “patients with E. coli infection” in ICU wards. The target thresholds were ％fT＞MIC＞50％ （piperacillin/tazobactam， cefoperazone/sulbactam），％fT＞MIC＞40％ （meropenem）， fcmax/MIC＞10 （amikacin）. The cumulative response percentage （CFR） to the target threshold requires that CFR be greater than 90％ for the optimal regimen. The results were compared with those of 275 clinical ICU pationts. RESULTS： Four antibiotics were identified， namely cefoperazone/sulbactam， piperacillin/tazobactam， meropenem and amikacin； sixteen medication regimen were simulated， including 1 kind of cefoperazone/sulbactam “3.0 g， q8 h”； 3 kinds of piperacillin/tazobactam “2.25 g，  q6 h” “3.375 g， q8 h” and “3.375 g， q6 h”； 2 kinds of meropenem “0.5 g， q8 h” “1.0 g， q8 h”； 3 kinds of amikacin “0.4 g， q24 h” “0.6 g， q24 h” and “0.8 g， q24 h”. Their CFR values were higher than 90％， all of them could be regarded as primary medication regimen. The clinical results were basically consistent with the simulation results. CONCLUSIONS： Above medication regimen of piperacillin/tazobactam， cefoperazone/sulbactam， meropenem and amikacin can be used as initial empirical drug selection for patients with E. coli infection in ICU.