Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.

The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.

Objective To investigate the effect of icotinib on right ventricular remodeling in rats with monocrotaline(MCT)-induced pulmonary hypertension(PH).Methods Sprague-Dawley rats were randomly divided into control group(0.3％sodium carboxymethyl cellulose),model group and low,high dose experimental groups(30,60 mg·kg-1 icotinib),8 rats in each group.PH rat model was established by single intraperitoneal injection of 60 mg·kg-1 MCT in model group and low,high dose experimental groups.The drug was administered continuously for 4 weeks after MCT injection.The hemodynamic indexes of each group were detected.Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL)staining was used to detect the apoptosis of right ventricular cardiomyocytes.The protein levels of B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved cysteine aspartic acid specific protease-3(cleaved-caspase-3),epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),optic atrophy 1(Opa1)and mitofusin 2(Mfn2)were detected by Western blot analysis.Results The right ventricular systolic pressure in low,high dose experimental groups and control group,model group were(38.58±4.98),(34.15±3.88),(23.66±2.45)and(45.07±5.78)mmHg;the mean pulmonary artery pressure were(27.85±3.77),(24.25±3.09),(17.33±2.46)and(33.07±4.15)mmHg;the right ventricle(RV)to left ventricle+septum were(36.38±5.51)％,(33.63±4.69)％,(22.25±2.96)％and(42.50±7.33)％;the RV to tibial length were(69.33±7.86),(62.69±7.17),(49.12±6.42)and(78.22±9.07)mg·cm-1.There were significant differences in the above indexes between low,high dose experimental groups and model group(all P＜0.01).There were significant differences in Bcl-2,Bax,cleaved caspase-3,p-EGFR,Opa1,Mfn2 between low,high dose experimental groups and model group(P＜0.05,P＜0.01).Conclusion Icotinib can inhibit right ventricular remodeling in PH rats induced by MCT,and its mechanism may be related to reducing the phosphorylation level of EGFR in the right ventricle,alleviating mitochondrial dysfunction and inhibiting cardiomyocyte apoptosis.

Objective:To analyze the efficacy and influencing factors of cyclosporine(CsA)alone in the treatment of children with acquired aplastic anemia(AA).Methods:The clinical data of children diagnosed with AA and treated with CsA alone from January 1,2016 to December 31,2020 in the Children's Hospital of Chongqing Medical University were collected,and the efficacy and influencing factors of CsA treatment were evaluated.Results:Among the 119 patients,there were 62 male and 57 female,with a median age of 7 years and 1 month.There were 45 cases of very severe AA(VSAA),47 cases of severe AA(SAA),and 27 cases of non-severe AA(NSAA).At 6 months after treatment,the efficacy of VSAA was lower than that of SAA and NSAA,and there was a statistical difference(P＜0.01).6 cases died early,16 cases relapsed,2 cases progressed to AML and ALL.The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA,while high PLT count was a protective factor(P=0.008,P=0.002).The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5 × 109/L,68.5％,respectively.Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST(P=0.020,OR=0.062),and high PLT count was a protective factor(P=0.044,OR=1.038).At 3 months of treatment,CsA response and NSAA were the risk factor for recurrence(P=0.001,0.031).Conclusion:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone.A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA,and a high proportion of bone marrow lymphocyte was an unfavorable factor.CsA response at 3 months and NSAA were risk factors for recurrence.

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
Humans ; Mice ; Animals ; Hyperalgesia/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Hypothermia/metabolism* ; Neuralgia ; Brachial Plexus/injuries* ; Edema/metabolism*

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.

Objective:To investigate the predictive value of different body obesity measures for non-alcoholic fatty liver disease (NAFLD).Methods:It was a cross-sectional study. The present study was a case-control study involving 553 subjects who underwent physical examination from January to April 2022. The subjects were divided into NAFLD group ( n=321 cases) and control group ( n=232 cases) according to abdominal ultrasound imaging parameters. All subjects completed a general information questionnaire, liver ultrasound examination, serum biochemical indices and physical measurements. Logistic regression model was used to analyze the correlation between human obesity measures (neck circumference, triceps skinfold thickness (TSF),body mass index (BMI), waist-to-hip ratio, lipid accumulation index (LAP), visceral fat index (VAI), body roundness index (BRI) and a body shape index (ABSI)) and NAFLD. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of single and combined measures of obesity for NAFLD. Results:The subjects were stratified by gender, and the quartile levels of BMI, neck circumference, TSF, waist-to-hip ratio, LAP, VAI and BRI were all correlated with NAFLD in both male and female (all P<0.05). After further adjustment for confounding factors, compared with those in group Q 1, group Q 4 of the above-mentioned indexes still had higher odds ratios ( P<0.05). The AUC value of LAP in predicting NAFLD was the largest in both men and women, which was 0.836(0.788-0.876) and 0.885(0.839-0.921), and the cut-off value was 41.93 and 33.27, respectively. There was no significant difference in AUC of ROC predicting NAFLD among LAP, BRI and BMI ( P>0.05). The AUC of ABSI in predicting NAFLD was less than 0.7(namely 0.584(0.525-0.641) and 0.679(0.618-0.735) in men and women, respectively), which indicated poor predictive performance for NAFLD. In the pairwise combination index, the AUC of ROC predicting NAFLD with TSF+LAP in male was the largest, which was 0.864(0.819-0.901), and there was statistical significance when compared with BRI (AUC=0.818(0.769-0.860)) and BMI (AUC=0.816(0.767-0.858)) ( P<0.05), but there was no statistical significance when compared with LAP (AUC=0.836(0.788-0.876)) ( P>0.05). The AUC of ROC predicting NAFLD with VAI+LAP in women was the largest, it was 0.894(0.849-0.928), there was statistical significance when compared with BMI (AUC=0.849(0.799-0.890)) ( P<0.05), but there was no statistical significance when compared with LAP (AUC=0.885(0.839-0.921)) and BRI (AUC=0.870(0.822-0.908)) ( P>0.05). Conclusion:BMI, neck circumference, TSF, waist-to-hip ratio, LAP, VAI and BRI all have good predictive value for NAFLD.

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ²=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female ; Humans ; Adult ; Medroxyprogesterone Acetate/adverse effects* ; Endometrial Hyperplasia/pathology* ; Dydrogesterone/adverse effects* ; Hyperplasia ; Prospective Studies