ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine （TCM）/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed， Embase， Web of Science， CNKI， Wanfang Data， and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1， 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ） and Reporting Items for Practice Guidelines in Healthcare （RIGHT）. ResultsA total of nine guidelines/consensuses were included after literature screening， with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows： scope and purpose （47.1%）， stakeholder involvement （41.0%）， rigor of development （21.6%）， clarity of presentation （40.2%）， applicability （19.0%）， and editorial independence （19.6%）. The recommendation level of the articles was B level （recommended after revision） for four articles and C level （not recommended） for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”， while other areas needed to be improved. Currently， there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness， scientific rigor， and transparency of these guidelines/consensuses.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective To analyze trend changes of disease burden of hypertensive nephropathy (HTN) between 2012 and 2023 in Chongqing, and to provide the suggestion for HTN prevention and treatment. Methods Death cases of HTN from Chongqing death registration data between 2012 and 2023 were analyzed to calculate indicators such as mortality, age standardization mortality rate (ASMR), rate of years of life lost (YLL) and Average years of life lost. The mortality of HTN between male and female, urban and rural were compared by Chi-square test. The trend change was explained by average annual percent of change (AAPC). Results The mortality and standardized mortality of HTN in Chongqing decreased from 5.44/100 000 and 3.13/100 000 in 2012 to 2.76/100 000 and 1.07/100,000 in 2023 respectively. The average annual percent change (AAPC) was -5.41% and -8.35% respectively, and the differences in the change trends were statistically significant (P<0.01). The mortality and standardized mortality of HTN in males and females decreased with AAPC of 5.50%, 8.07%, 5.27% and 8.69% respectively, and the differences in the change trends were all statistically significant (all P< 0.05). From 2012 to 2014, 2019 and 2021, the mortality rate of HTN in rural areas was higher than that in urban areas (all P < 0.05). The mortality and standardized mortality of HTN in rural areas decreased with AAPC of 6.58% and 9.46% respectively, and the differences in the change trends were all statistically significant (all P<0.05). The rate of YLL and standardized YLL of HTN in Chongqing decreased from 96.02/100 000 and 60.42/100 000 in 2012 to 44.98/100 000 and 21.49/100 000 in 2023 respectively. The AAPC was -5.83% and -7.80% respectively, and the differences in the change trends were statistically significant (both P < 0.05). AYLL of HTN were 17.88 years in 2012, and it was 17.08 years in 2023. There were no statistically significant differences in the changes (both P > 0.05). The standardized AYLL of HTN in rural areas increased at an average annual rate of 1.14%, and the difference was statistically significant (P < 0.05). Conclusion The mortality and YLL rate of HNT in Chongqing was lower than it in China. Moreover, its trend was decreased. It should be strengthened early screening and healthy management of HNT.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*