A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

Objective:To investigate the mechanism by which baicalein alleviates osteoarthritis by regulating Sirtuin (Sirt) to inhibit the senescence of fibroblast-like synoviocytes (FLS).Methods:FLS were extracted from synovium of non-osteoarthritis patients (3 patients) and osteoarthritis patients (3 patients), and assessed the senescence of FLS in osteoarthritis patients by Western blot, β-galactosidase staining and immunofluorescence, and examined the changing levels of Sirt family proteins and mRNAs in FLS. The relative expression level of Sirt1 in FLS was knocked down by transfection with Sirt1 siRNA, and the antioxidative capacity and senescence degree of FLS were analyzed. Chondrocytes were co-cultured with FLS and functional changes in chondrocytes were detected by Western blot. After inducing FLS senescence with bleomycin (BLM), different concentrations of baicalein were administered to detect the expression levels of Sirt1, p16, and p21 proteins and intracellular reactive oxygen species (ROS). The expression level of Sirt1 in FLS was knocked down, and BLM and baicalein treatments were applied. The relative expression levels of Sirt1 and ROS were detected using Western blot and ROS assays. After BLM-induced FLS senescence, baicalein and Compound C were added. The relative expression levels of phosphorylated AMP-activated protein kinase (pAMPK), nuclear factor erythroid 2-related factor 2 (NRF2), p16, p21, and ROS were detected by Western blot and ROS assays.Results:The relative expression of p16 and p21 in FLS in the osteoarthritic group were 3.66±0.38 and 3.55±0.34, which were higher than those in non-osteoarthritis group 1.00±0.07 and 1.00±0.09 ( t=11.860, P<0.001; t=12.520, P<0.001). The relative expression levels of Sirt1 and Sirt6 in FLS in the osteoarthritis group were 0.30±0.04 and 0.16±0.01, which were smaller than those in the non-osteoarthritis group 1.00 ± 0.03 and 1.00±0.04 ( t=23.840, P<0.001; t=34.130, P<0.001). After baicalein treatment, the relative expression of ROS was 2.58±0.28, 1.65±0.14 and 1.00±0.24 in the BLM, BLM+Bai and control groups, respectively, with statistically significant differences between the groups ( F=35.700, P<0.001), which was greater in the BLM and BLM+Bai than in the control group, and lower in the BLM+Bai than in the BLM group ( P<0.05). The relative expression of pAMPK and NRF2 was 0.28±0.02 and 0.38±0.09 after Compound C+Baicalein treatment, which was lower than that of 0.56±0.07 and 0.60±0.08 in the BLM+Bai group ( P<0.05). The relative expression of ROS increased from 1.75±0.16 to 3.45±0.12 ( P<0.001). The proportion of positivity in the BLM+Bai+Compound C, BLM+Bai and control groups was 47.30%±4.29%, 18.18%±3.89% and 7.70%±3.53% ( F=109.700, P<0.001), respectively, with the BLM+Bai+Compound C group being higher than that in the BLM+Bai group ( P<0.05). Conclusion:The downregulation of Sirt1 expression in patients with osteoarthritis leads to FLS senescence and accelerates the progression of osteoarthritis. Baicalein can inhibit FLS senescence by activating Sirt1/AMPK/NRF2 pathway, which may delay the progression of osteoarthritis and improve the function of chondrocytes.

Objective:RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia(B-ALL)and explore the possible mechanisms of drug resistance.Methods:RS4;11 cell line was continuously induced and cultured by low and ascending concentrations of BCL-2 inhibitors navitoclax and venetoclax to construct navitoclax-resistant cell line RS4;11/Nav and venetoclax-resistant cell line RS4;11/Ven.The cell viability was detected by MTT assay,and the cell apoptosis was detected by flow cytometry.Differentially expressed genes(DEGs)between RS4;11 drug-resistant cell lines and parental cell line were detected by transcriptome sequencing technology(RNA-seq),and mRNA expression levels of DEGs between drug-resistant cell lines and parental cell line were detected by real-time PCR(RT-PCR).Western blot was used to detect the expression levels of BCL-2 family anti-apoptotic proteins in drug-resistant cell lines and parental cell line.Results:The drug-resistant cell lines RS4;11/Nav and RS4;11/Ven were successfully established.The resistance index(RI)of RS4;11/Nav to navitoclax and RS4;11/Ven to venetoclax was 328.655±47.377 and 2 894.027±300.311,respectively.The results of cell apoptosis detection showed that compared with the drug-resistant cell lines,RS4;11 parental cell line were significantly inhibited by BCL-2 inhibitors,while the apoptosis rate of drug-resistant cell lines was not affected by the drugs.Western blot assay showed that the expression of anti-apoptotic proteins of BCL-2 family did not increase significantly in drug-resistant cell lines.RNA-seq,RT-PCR and Western blot assays showed that the expression of EP300 in drug-resistant cell lines was significantly higher than that in parental cell line(P＜0.05).Conclusion:Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors,and the drug resistance mechanism may be related to the overexpression of EP300.

Objective To observe the clinical efficacy of Redo-Bentall surgery in the reoperation of aortic root lesions.Methods A retrospective analysis was performed on 46 patients who underwent Redo-Bentall surgery for aortic root lesions in our department from June 2010 to April 2022.They were 35 males and 11 females,at a mean age of 43.37±12.79 years,in 4.96±6.76 years since the last operation.General clinical data in perioperative period and during follow-up were collected and analyzed.Kaplan-Meier survival analysis was used to compare the survival rates of each etiological group.Results There were 9 cases of central end otitis,12 cases of Behset's disease,and 25 cases of other causes.After operation,4 cases(8.70％)experienced cardiac arrest,4 cases(8.70％)renal failure,2 cases(4.35％)gastrointestinal bleeding,2 cases(4.35％)new third-degree atrioventricular block and 2 cases(4.35％)permanent pacemaker placement.In perioperative period,3 cases(6.52％)died in hospital.During a mean follow-up of 5.03±3.27 years after discharge,5 cases(11.63％)were lost to follow-up,1 case died(2.33％),1 case had lacunar infarction(2.33％),and no severe bleeding or embolism complications was observed in the rest patients.The long-term survival rate was significantly lower in the endocarditis group(62.3％)and the Behcet's disease group(70％)than the other etiological groups(80％,P＜0.05).Conclusion The application of Redo-Bentall in the reoperation of aortic root lesions is safe and effective,but the survival rate is quite lower in the patients with infective endocarditis and Behcet's disease.

Objective To investigate the therapeutic effect of hesperidin(Hsp)on mammary gland hyperplasia(MGH)rats and the possible mechanism.Methods Sixty female rats were randomly divided into blank,model,control and experimental-L,-M,-H groups.Except for blank group,all other groups were injected intramuscularly with estrogen and progestin to induce MGH model in rats.The experimental-L,-M and-H groups were given 25,50,100 mg·kg-1 Hsp by gavage.The control group was given 5 mg·kg-1 tamoxifen by gavage.The blank and control groups were given an equal volume of 0.9％NaCl by gavage.Six groups of rats were administered once a day for 30 days.After the administration,the height and diameter of nipples and the uterine coefficient were measured.The serum sex hormone content was detected using enzyme-linked immunosorbent assay,the levels of oxidative stress indicators were detected using corresponding kits,and the expressions of related proteins were detected using Western blot.Results The nipple diameters of rats in experimental-M and-H groups,control group,model group and blank group were(1.41±0.20),(1.18±0.21),(1.23±0.20),(1.75±0.13)and(1.02±0.06)mm;the nipple heights were(1.62±0.24),(1.41±0.19),(1.47±0.16),(1.87±0.32)and(1.23±0.14)mm;the uterine indexes were(0.55±0.08),(0.37±0.05),(0.41±0.04),(0.72±0.11)and(0.34±0.03)mg·g-1;the relative expression levels of estrogen receptor alpha(ERα)were 0.54±0.05,0.13±0.02,0.13±0.03,0.89±0.08 and 0.10±0.02;the relative expression levels of progesterone receptor(PR)were 0.43±0.03,0.08±0.01,0.87±0.07,0.20±0.04 and 0.14±0.03;the phosphorylated-extracellular-regulated kinase 1/2(ERK1/2)/ERK1/2 were 0.50±0.03,0.06±0.02,0.83±0.05,0.09±0.04 and 0.04±0.01,respectively.Compared with model group,the differences of above indexes in the experimental-M,-H groups and control group were statistically significant(all P＜0.05).Conclusion Hsp could reduce nipple diameter,height,and uterine coefficient,regulate sex hormone levels,resist oxidative stress,and inhibit the expression of ERα,PR and p-ERK1/2 proteins in rats.

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.
Humans ; Medicine, Chinese Traditional ; Gastrointestinal Tract ; Skin Diseases/drug therapy* ; Gastrointestinal Microbiome

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.
Humans ; Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Molecular Docking Simulation ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Capsules ; Atherosclerosis ; Cerebral Infarction ; Neoplasms

BACKGROUND: Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility, bringing serious harm to women's physical and mental health. Acupuncture may be an effective treatment for PCOS. However, systematic reviews (SRs) on the efficacy and safety of acupuncture for PCOS have reported inconsistent results, and the quality of these studies has not been adequately assessed. OBJECTIVE: To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS, as well as to assess the quality and risks of bias of the available SRs. SEARCH STRATEGY: Nine electronic databases (Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Chinese Science and Technology Periodical Database, and China Biology Medicine disc) were searched from their establishment to July 27, 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "acupuncture," "polycystic ovary syndrome," and "systematic review." INCLUSION CRITERIA: SRs of randomized controlled trials that explored the efficacy and (or) safety of acupuncture for treating patients with PCOS were included. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted study data according to a predesigned form. Tools for evaluating the methodological quality, risk of bias, reporting quality, and confidence in study outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), were used to score the included SRs. RESULTS: A total of 885 studies were retrieved, and 11 eligible SRs were finally included in this review. The methodological quality of 2 SRs (18.18%) was low, while the other 9 SRs (81.82%) were scored as extremely low. Four SRs (36.36%) were considered to be of low risk of bias. As for reporting quality, the reporting completeness of 9 SRs (81.82%) was more than 70%. Concerning the confidence in study results, 2 study results were considered to have a high quality of evidence (3.13%), 14 (21.88%) a "moderate" quality, 28 (43.75%) a "low" quality, and 20 (31.24%) considered a "very low" quality. Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate (CPR) and ovulation rate, and reduce luteinizing hormone/follicle-stimulating hormone ratio, homeostasis model assessment of insulin resistance, and body mass index (BMI). When compared with medicine alone, acupuncture alone also can improve CPR. Further, when compared with no intervention, acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI. Acupuncture was reported to cause no adverse events or some adverse events without serious harm. CONCLUSION The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence. More high-quality studies are needed to support the use of acupuncture in PCOS.
Pregnancy ; Humans ; Female ; Polycystic Ovary Syndrome/etiology* ; Acupuncture Therapy/adverse effects* ; Infertility, Female/etiology* ; China