Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

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.

Research on analgesic effect and prospect of clinical application of rutin / 中国药理学通报

Rutin is extracted from Ruta graveolens L. with many pharmacological activities such as anti-inflammation, anti-oxidation , protecting cardiovascular system and analgesia. As a natural product, rutin has the advantages of low side effects and difficult tolerance, but its instability and low bioavailability still limit its clinical application. This paper summarizes the analgesic mechnism of rutin, and looks forward to the clinical applica¬tion of rutin based on its derivative and dosage forms. It is expected to provide ideas for further analgesic research and drug development and application of rutin in the future.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

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.

Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

Research advances of adipose stem cell matrix gel in promoting wound healing / 中华烧伤杂志

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis / 中华内科杂志

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Analysis on survival time and influencing factors among reported HIV/AIDS in Yunnan Province, 1989-2021 / 中华流行病学杂志

Objective: To analyze the survival time of reported HIV/AIDS and influencing factors of Yunnan Province from 1989 to 2021. Methods: The data were extracted from the Chinese HIV/AIDS comprehensive response information management system. The retrospective cohort study was conducted. The life table method was applied to calculate the survival probability. Kaplan-Meier was used to draw survival curves in different situations. Furthermore, the Cox proportion hazard regression model was constructed to identify the factors related to survival time. Results: Of the 174 510 HIV/AIDS, the all-cause mortality density was 4.23 per 100 person-years, the median survival time was 20.00 (95%CI:19.52-20.48) years, and the cumulative survival rates in 1, 10, 20, and 30 years were 90.75%, 67.50%, 47.93% and 30.85%. Multivariate Cox proportional risk regression model results showed that the risk of death among 0-14 and 15-49 years old groups were 0.44 (95%CI: 0.34-0.56) times and 0.51 (95%CI:0.50-0.52) times of ≥50 years old groups. The risk for death among the first CD4+T lymphocytes counts (CD4) counts levels of 200-349 cells/μl, 350-500 cells/μl and ≥501 cells/μl groups were 0.52 (95%CI: 0.50-0.53) times, 0.41 (95%CI: 0.40-0.42) times and 0.35 (95%CI: 0.34-0.36) times of 0-199 cells/μl groups. The risk of death among the cases that have not received antiretroviral therapy (ART) was 11.56 (95%CI: 11.26-11.87) times. The risk for death among the cases losing to ART, stopping to ART, both losing and stopping ART was 1.66 (95%CI:1.61-1.72) times, 2.49 (95%CI:2.39-2.60) times, and 1.65 (95%CI:1.53-1.78) times of the cases on ART. Conclusions: The influencing factors for the survival time of HIV/AIDS cases were age at diagnosis in Yunnan province from 1989 to 2021. The first CD4 counts levels, antiretroviral therapy, and ART compliance. Early diagnosis, early antiretroviral therapy, and increasing ART compliance could extend the survival time of HIV/AIDS cases.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Independent prognostic value of the congestion and renal index in patients with acute heart failure / 老年心脏病学杂志（英文版）

BACKGROUND@#Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF.@*METHODS@#We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes.@*RESULTS@#A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system.@*CONCLUSIONS@#In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma / 中西医结合学报

OBJECTIVE@#Although there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.@*METHODS@#Small interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.@*RESULTS@#JAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.@*CONCLUSION@#JAML is a novel target for kaempferol against LUAD cells. Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268-276.

Endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.

Analysis of the pollution status of paralytic shellfish poisons in shellfish sold in Hainan Province, 2018-2021 / 中国热带医学

@#Abstract: Objective　To investigate the pollution of paralytic shellfish poisons (PSP) in shellfish sold in Hainan Province from 2018 to 2021. Methods　From 2018 to 2021, the content of 10 paralytic shellfish poisons including saxitoxin (STX), neosaxitoxin (neoSTX), gonyautoxins 1 (GTX1), gonyautoxins 2 (GTX2), gonyautoxins 3 (GTX3), gonyautoxins 4 (GTX4), gonyautoxins 5 (GTX5), decarbamoylsaxitoxin (dcSTX), decarbamoylgonyau toxins 2 (dcGTX2) and decarbamoylgonyau toxins 3 (dcGTX3) in 7 kinds of shellfish commonly sold in 13 cities and counties in Hainan province was analyzed. Results　The detection rate of PSP in 360 shellfish samples was 10.3%. Among them, the highest detection rate of STX was 5.83%, followed by GTX2 detection rate of 4.17%; the detection rate of neoSTX and GTX3 were both 1.67%; the detection rate of GTX1 was 1.39%. None of the five PSP, GTX4, GTX5, dcSTX, dcGTX2 and dcGTX3, were detected. Four types of PSP were detected in fanscallops, two were detected in oysters, mussels and Scapharca subcrenata, only one was detected in scallops, and no toxin contamination was detected in clams and razor clams. A single sample of fanscallops detected a maximum of 4 PSP, and a single sample of oysters, scallops, mussels and Scapharca subcrenata detected a maximum of 1 PSP. The equivalence of PSP in all samples was ND-155.6 μg/kg.The annual detection rate of PSP from high to low was: 20.0% in 2020, 15.6% in 2019, 5.3% in 2018, and 2.0% in 2021, and none of the samples tested exceeded the standard. Continuously detectable STX in 2018-2020, all PSP that could be detected in 2018 were STX. In 2019, in addition to STX detected in scallops and Scapharca subcrenata, neoSTX was also detected in oysters, mussels and Scapharca subcrenata. In 2020, PSP was only detected from scallops, and GTX2 could be detected in all positive specimens, while 5 STX, 5 GTX1 and 6 GTX3 were detected. Only GTX2 detected from scallops in 2021. STX was detected in shellfish sold in 12 cities and counties, GTX2 can be detected in 10 cities and counties, neoSTX can be detected in 5 cities and counties, GTX1 and GTX2 were detected in 4 cities and counties respectively. Shellfish sold in Wenchang and Lingshui markets can detect 5 types of PSP. Conclusion　Some types of shellfish on the market in Hainan are contaminated with some kind of PSP pollution risks, and it is necessary to strengthen the supervision of PSP in marketed shellfish.

Research progress of a new immune checkpoint inhibitor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain in anti-tumor immunotherapy / 中国热带医学

@#The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells (NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells. TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies (mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC) patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.

Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.

Influence of visceral lipids obesity on the early postoperative complications after radical gastrectomy / 中华胃肠外科杂志

Objective: To investigate the effect of visceral fat area (VFA) on the surgical efficacy and early postoperative complications of radical gastrectomy for gastric cancer. Methods: A retrospective cohort study method was used. Clinicopathological data and preoperative imaging data of 195 patients who underwent D2 radical gastric cancer surgery at the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to December 2017 were analyzed retrospectively. Inclusion criteria: (1) complete clinicopathological and imaging data; (2) malignant gastric tumor diagnosed by preoperative pathology, and gastric cancer confirmed by postoperative pathology; (3) no preoperative complications such as bleeding, obstruction or perforation, and no distant metastasis. Those who had a history of abdominal surgery, concurrent malignant tumors, poor basic conditions, emergency surgery, palliative resection, and preoperative neoadjuvant therapy were excluded. The VFA was calculated by software and VFA ≥ 100 cm2 was defined as visceral obesity according to the Japan Obesity Association criteria . The patients were divided into high VFA (VFA-H, VFA≥100 cm2, n=96) group and low VFA (VFA-L, VFA<100 cm2, n=99) group . The clinicopathological characteristics, surgical outcomes and early postoperative complications were compared between the two groups. Univariate and multivariate Logistic regression models were used to analyze the risk factors of early complications. Receiver operating characteristic (ROC) curve was used to analyze predictive values of VFA for early complications. Pearson's χ2 test was used to analyze the correlation between BMI and VFA. Results: There were no significant differences in terms of gender, age, American Society of Anesthesiologists physical status classification, preoperative comorbidities, preoperative anemia, tumor TNM staging, N staging, T staging and tumor differentiation, surgical method, extent of resection, and tumor location between the VFA-L group and the VFA-H group (all P>0.05). However, patients in the VFA-H group had higher BMI, larger tumor, lower rate of hypoalbuminemia and greater subcutaneous fat area (SFA) (all P<0.05). The VFA-H group presented significantly longer operation time and significantly less number of harvested lymph nodes as compared to the VFA-L group (both P<0.05). However, there were no significant differences in intraoperative blood loss, conversion to laparotomy and postoperative hospital stay (all P>0.05). Complications of Clavien-Dindo grade II and above within 30 days after operation were mainly anastomosis-related complications (leakage, bleeding, infection and stricture), intestinal obstruction and incision infection. The VFA-H group had a higher morbidity of early complications compared to the VFA-L group [24.0% (23/96) vs 10.1% (10/99), χ2=6.657, P=0.010], and the rates of anastomotic complications and incision infection were also higher in the VFA group [10.4% (10/96) vs. 3.0% (3/99), χ2=4.274, P=0.039; 7.3% (7/96) vs. 1.0% (1/99), P=0.033]. Multivariate logistic analysis showed that high BMI (OR=3.688, 95%CI: 1.685-8.072, P=0.001) and high VFA (OR=2.526, 95%CI: 1.148-5.559,P=0.021) were independent risk factors for early complications. The area under the ROC curve (AUC) of VFA for predicting early complications was 0.645, which was higher than that of body weight (0.591), BMI (0.624) and SFA (0.626). Correlation analysis indicated that there was a significantly positive correlation between BMI and VFA (r=0.640, P<0.001). Conclusion: VFA ≥ 100 cm2 is an independent risk factor for early complications after radical gastrectomy for gastric cancer.It can better predict the occurrence of above early postoperative complications.

Research progress on DNA methylation in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

DNA methylation, as an important form of epigenetic modification, plays vital roles in the occurrence and development of diseases by regulating gene expression. In recent years, with the rapid development of DNA methylation research and the continuous updates of the detection method,it is reported that DNA methylation has become an important way to explore the pathogenesis of various diseases and new treatment methods.Many breakthroughs have been made in the basic research of DNA methylation in different ophthalmological diseases, including corneal epithelium repair, cell adhesion and abnormal matrix remodeling of conjunctival epithelium, ocular fibrosis and glaucoma, oxidative stress, inflammatory response and cell damage, the relationship between different DNA methylation levels and ocular tumors, etc. This review aims to provide a new idea for the pathogenesis, examination, diagnosis and prevention of different ocular diseases by summarizing the relevant studies on the regulatory mechanisms of DNA methylation in ophthalmological diseases.

Research Progress on the Application of Human Oral Microbiome in Forensic Individual Identification / 法医学杂志

The oral cavity is the second largest microbial bank in humans after the intestinal canal, colonizing a large number of microorganisms including viruses, bacteria, archaea, fungi and protozoa. The great number of microbial cells, good DNA stability, and individual has a unique microbial community, these characteristics make the human microbiome expected to become a new biomarker for forensic individual identification. This article describes the characteristics of human oral microorganisms and microbial molecular markers in detail, analyzes the potential application value of microorganisms in forensic individual identification, and reviews the research progress of human oral microorganisms in forensic individual identification.

Interaction between ischemic stroke risk loci identified by genome-wide association studies and sleep habits / 北京大学学报(医学版)

OBJECTIVE@#To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci.@*METHODS@#A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke.@*RESULTS@#A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033).@*CONCLUSION@#Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.

Content Difference of Effective Components of Cynomorii Herba Between Different Producing Areas and Its Response to Environmental Factors / 中国实验方剂学杂志

ObjectiveTo explore the content difference of gallic acid，protocatechuic acid，catechin，total flavonoids， and total polysaccharides in Cynomorii Herba between different producing areas and the correlation between effective components and environmental factors. MethodNinety-five batches of Cynomorii Herba samples were collected from 12 major producing areas in five provinces （autonomous regions）， including Gansu，Inner Mongolia，Xinjiang，Qinghai， and Ningxia，and the geographical-climatic factors such as altitude，longitude and latitude，climate type，annual average frost-free period，annual rainfall，annual sunshine hours，annual average temperature， and annual average evaporation were recorded. The content of gallic acid，protocatechuic acid， and catechin in Cynomorii Herba was determined by high-performance liquid chromatography （HPLC），and the mathematical model of the correlation between the content of chemical components and environmental factors was optimized and established. ResultPearson correlation analysis showed that protocatechuic acid content in Cynomorii Herba increased with the increase in annual average frost-free period and annual average temperature， and catechin content increased with the increase in the annual average frost-free period，annual sunshine hours， and annual average evaporation，while total polysaccharides content decreased with the increase in altitude. Redundancy analysis （RDA） showed that the annual average frost-free period， annual average evaporation，annual sunshine hours， and altitude had great influences on the content of effective components in Cynomorii Herba. Curve fitting showed that the optimal conditions for the growth of Cynomorii Herba were as follows： altitude of 800-2 000 m，annual average frost-free period of 80-110 d， annual rainfall of 110-300 mm，annual sunshine hours of 2 400-3 000 h， annual average temperature of 2.2-8.8 ℃，and annual average evaporation of 1 700-2 500 mm. ConclusionThe content of effective components in Cynomorii Herba is diverse in terms of producing areas and shows a clear response rule to environmental factors. The areas suitable for growing and artificial cultivation introduction are those with high altitude，short annual average frost-free period，low annual rainfall，large average evaporation，long sunshine hours， and low annual average temperature.

Analysis of Chemical Constituents in Different Parts of Gentiana straminea Based on UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） was used to analyze the chemical constituents in the aerial part and roots of Gentiana straminea from different areas of Qinghai province， and the main chromatographic peaks and differential components of different parts were identified. MethodThe chromatographic separation was performed on a Waters ACQUITY UPLC HSS T3 column （2.1 mm×100 mm， 1.8 μm） with 0.1% formic acid aqueous solution （A）-acetonitrile （B） as the mobile phase for gradient elution （0-1 min， 1%-13%B； 1-5 min， 13%-18%B； 5-7 min， 18%-50%B； 7-9.5 min， 50%-60%B； 9.5-11 min， 60%-99%B； 11-14 min； 99%B； 14-15 min， 99%-1%B； 15-16 min， 1%B）， the column temperature at 40 ℃， and the flow rate of 0.3 mL·min-1. Electrospray ionization （ESI） and negative ion full scan mode were selected for the mass spectrometric conditions to analyze the samples， and the detection range was m/z 50-1 200. Chemical constituents of the aerial part were qualitatively analyzed with the reference substances， literature information and ChemSpider. Principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were used to analyze the classification trend， correlation and differential chemical components between aerial part and roots of G. straminea. ResultA total of 68 components， including 24 iridoids， 13 flavonoids， 8 triterpenoids， 6 xanthones， 5 fatty acids， 4 saccharides， 3 phenolic glycosides， 2 alkaloids， 2 sterols and 1 lignan， were preliminarily identified from the aerial part of G. straminea. Among them， 42 components were firstly reported in 4 Gentiana species included in the 2020 edition of Chinese Pharmacopoeia. Eight differential components were screened out， namely sucrose， maltotriose， loganic acid， shanzhiside methyl ester， 6′-O-β-D-glucosylgentiopicroside， swertiamarin， gentiopicrin and isovitexin. ConclusionThe aerial part of G. straminea is rich in chemical constituents and has good medicinal potential. There were significant differences in the chemical components between the aerial part and roots of G. straminea， and the main differential components were iridoids， which could provide a basis for exploring efficacy differences in different parts of G. straminea.