Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Association between chlamydia pneumoniae, mycoplasma infection and atherosclerosis / 公共卫生与预防医学

Objective To investigate the infection of Chlamydia pneumoniae and mycoplasma pneumoniae in adults and their association with atherosclerosis,and to provide theoretical guidance for the prevention of such diseases. Methods A case-control study was used to collect 362 patients who were diagnosed with atherosclerosis from January 2019 to December 2021 in Department of Sichuan Bazhong Central Hospital, and 370 cases who were admitted to the hospital during the same period of physical examination without any cardiovascular disease were selected as the control group, and whole blood samples of the two groups of study subjects were collected, and the infection of Chlamydia pneumoniae and mycoplasma pneumoniae was detected by PCR. Results The infection rate of Chlamydia pneumoniae was 35.49%, the infection rate of mycoplasma was 40.37%, and the co-infection rate was 11.37%；The infection rate of Chlamydia pneumoniae in the control group was 12.04%, the infection rate of mycoplasma was 15.83%, and the coinfection rate was 3.14%, and the difference between the two groups was statistically significant ( χ2=10.926, P=0.023). The effects of mycoplasma, chlamydia, and co-infection on atherosclerotic patients have sex differences, mainly manifested as higher infection rates in men; In addition, the effects of mycoplasma, chlamydia, and co-infection on atherosclerosis patients varied by age, mainly in the 55-70 years age group (P<0.05). Multivariate logistic regression results showed that Chlamydia pneumoniae infection was a risk factor for atherosclerosis (OR=1.303, 95%CI: 1.043-1.677) in the whole population, and chlamydia pneumoniae (OR=1.472, 95% CI: 1.037-1.556), mycoplasma (OR=2.003, 95%CI: 1.637-3.842) and co-infection in men (OR=1.937, 95%CI: 1.380-2.184) were risk factors for atherosclerosis, while co-infection in women (OR=1.699, 95%CI: 1.263-1.765) was a risk factor for atherosclerosis. Conclusion Chlamydia pneumoniae and mycoplasma infection are risk factors for atherosclerosis, and their impact on male groups is greater, and more attention needs to be paid to them.

Effect of microRNA-138 regulation of Wnt pathway on the biological behavior of human glioma cells in vitro / 解剖学报

Objective To investigate the effect of microRNA (miR)-138 regulation of Wnt signaling pathway on the biological behavior of human glioma cells in vitro. Methods Glioma cell lines U-87MG and U251 were selected and randomly divided into blank group, miR-NC group, miR-138 mimics group and miR-138 inhibitor group. Real-time PCR was used to detect the miR-138 expression in each group; MTT, flow cytometry, Transwell assay and scratch assay were used to detect proliferation, apoptosis, invasion and migration ability of each group respectively, and Western blotting was used to detect Wnt pathway-related protein expression in each group. Results The miR-138 expression level was higher in the miR-138 mimics group compared with the remaining 3 groups, and that in the miR-138 inhibitor group was lower than that in the blank group and the miR-NC group (P<0. 05) ; Compared with the blank group, the cell proliferation rate was lower in the miR-138 mimics group and higher in the miR-138 inhibitor group, and was time-dependent (P<0. 05) ; The apoptosis rate in the miR-138 mimics group was higher than that in the blank group, miR-NC group, and miR-138 inhibitor group, while the apoptosis rate in the miR-138 inhibitor group was lower than that in the rest other groups (P<0. 05) ; The number of cell-invading cells in the miR-138 mimics group was lower than that in the blank group, miR-NC group, and miR-138 inhibitor group, while all miR-138 inhibitor group were higher than the remaining three groups (P<0. 05) ; The cell migration rate of miR-138 mimics group was lower than that of blank group, miR-NC group and miR-138 inhibitor group, while all miR-138 inhibitor group were higher than the remaining three groups (P<0. 05) ; Wnt3a, Wntl, glycogen synthase kinase 3(3(GSK-3(3) and (3-catenin protein expression in the miR-138 mimics group was lower than that in the blank group, miR-NC group, and miR-138 inhibitor group; While miR-138 inhibitor groups were higher than the remaining three groups(P<0. 05). Conclusion MiR-138 overexpression effectively inhibite the proliferation, invasion and migration of glioma cells and promote their apoptosis, probably achieved by pathway inhibition of the Wnt signaling pathway.

Research progress of circular RNA in drug resistance of liver cancer / 中国药理学通报

Circular RNAs are novel non-coding RNAs with multiple biological functions, which can participate in biological processes such as the occurrence, development, invasion, and metastasis of liver cancer, as well as drug resistance of liver cancer. This article reviews the roles and mechanisms of circR-NAs in chemotherapy resistance, targeted therapy resistance and immunotherapy resistance in liver cancer, in order to provide new ideas for solving liver cancer resistance.

Artesunate inhibits development of esophageal squamous cell carcinoma via regulating expression of Skp2 and P21 / 中国药理学通报

Aim To clarify the regulatory effect of Artesunate(ART) on tumor cell function and cell cycle in the pathological process of esophageal squamous cell carcinoma(ESCC). Methods KYSE450 and TE14 cells were treated with different concentrations of ART. The cells treated with 0 mg •L

Prognostic comparison of active surveillance and adjuvant chemotherapy in the treatment of patients with stage Ⅰ ovarian immature teratoma after fertility-sparing surgery / 中华妇产科杂志

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

The Clinical Observation of Inflammation Theory for Depression:The Initiative of the Formosa Long COVID Multicenter Study (FOCuS)

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years / 中国中药杂志

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, β-amyloid(Aβ), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.

Efficacy and safety of acupuncture for polycystic ovary syndrome: An overview of systematic reviews / 中西医结合学报

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.

Application of fascial space priority approach for pelvic exenteration / 中华胃肠外科杂志

Locally advanced tumor with involvement of surrounding tissues and organs is a common situation in pelvic malignancies. Up to 10% of newly diagnosed rectal cancer cases infiltrate to adjacent tissues and organs. Satisfactory resection margins obtained by pelvic exenteration can achieve a 5-year survival rate similar to cases that without adjacent tissue invasion. The 5-year survival rate of patients with locally recurrent pelvic malignancies is almost zero if they are treated only with radiotherapy and chemotherapy. To obtain negative margins through pelvic exenteration is the only chance for a long-term survival of these patients. However, pelvic exenteration is a complicated procedure with higher morbidity and mortality. The development of fascia anatomy enables surgeons to have a deeper understanding and comprehensive application of pelvic fasciae. Meanwhile, the improvement of laparoscopic technology provides a clearer view for surgeons and enables the application of minimally invasive techniques in complex pelvic exenteration. The fascial space priority approach is based on the fascia anatomy of pelvis and giving priority to the separation of the pelvic avascular fascial spaces, which provides a reproducible surgical approach for complex pelvic exenteration.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Predictive value of foramen ovale size on pain recurrence after percutaneous balloon compression / 中南大学学报(医学版)

OBJECTIVES@#Primary trigeminal neuralgia (PTN) is a common cranial nerve disease in neurosurgery, which seriously endangers the physical and mental health of patients. Percutaneous balloon compression (PBC) has become an effective procedure for the treatment of PTN by blocking pain conduction through minimally invasive puncture. However, the recurrence of facial pain after PBC is still a major problem for PTN patients. Intraoperative balloon shape, pressure and compression time can affect the prognosis of patients with PBC after surgery. The foramen ovale size has an effect on the balloon pressure in Meckel's lumen. This study aims to analyse the predictive value of foramen ovale size for postoperative pain recurrence of PBC by exploring the relationship between foramen ovale size and postoperative pain recurrence of PBC.@*METHODS@#A retrospectively analysis was conducted on the clinical data of 60 patients with PTN who were treated with PBC in Department of Neurosurgery, Affiliated Hospital of Chengde Medical College from November 2018 to December 2021. We followed-up and recorded the Barrow Neurological Institute (BNI) pain score at 1, 3, 6 and 12 months after operation. According to the BNI pain score at 12 months after surgery, the patients were divided into a cure group (BNI pain score I to Ⅱ) and a recurrence group (BNI pain score Ⅲ to Ⅴ). The long diameter, transverse diameter and area of foramen ovale on the affected side and the healthy side of the 2 groups were measured. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used for analysis the relationship between the recurrence of pain and the long diameter, transverse diameter, area of foramen ovale on the affected side, and aspect ratio, transverse diameter ratio, area ratio of foramen ovale on the affected side to healthy side in the 2 groups.@*RESULTS@#At the end of 12 months of follow-up, 50 (83.3%) patients had pain relief (the cured group), 10 (16.7%) patients had different degrees of pain recurrence (the recurrence group), and the total effective rate was 83.3%. There were no significant differences in preoperative baseline data between the 2 groups (all P>0.05). The long diameter of foramen ovale on the affected side, the long diameter ratio and area ratio of foramen ovale on the affected/healthy side in the cured group were significantly higher than those in the recurrence group (all P<0.05), and there were no significant differences in the transverse diameter and area of foramen ovale on the affected side and the transverse diameter ratio of foramen ovale on the affected/healthy side between the 2 groups (all P>0.05). The ROC curve analysis showed that the AUC of the long diameter of foramen ovale on the affected side was 0.290 (95% CI 0.131 to 0.449, P=0.073), and the AUC of aspect ratio of foramen ovale on the affected side to healthy side was 0.792 (95% CI 0.628 to 0.956, P=0.004). The AUC of area ratio of foramen ovale on the affected side to healthy side was 0.766 (95% CI 0.591 to 0.941, P=0.008), indicating that aspect ratio and area ratio of foramen ovale on the affected side to healthy side had a good predictive effect on postoperative pain recurrence of PBC. When aspect ratio of foramen ovale on the affected side to healthy side was less than 0.886 3 or area ratio of foramen ovale on the affected side to healthy side was less than 0.869 4, postoperative pain recurrence was common.@*CONCLUSIONS@#Accurate evaluation of the foramen ovale size of skull base before operation is of great significance in predicting pain recurrence after PBC.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup / 中国结合医学杂志

OBJECTIVE@#To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients.@*METHODS@#By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup.@*RESULTS@#Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens.@*CONCLUSIONS@#There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

A circRNA-miRNA-mRNA network analysis underlying pathogenesis of human heart failure / 老年心脏病学杂志（英文版）

BACKGROUND@#The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF.@*METHODS & RESULTS@#We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively.@*CONCLUSION@#These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

Mid-term clinical outcome of arthroscopic surgery on early knee osteoarthritis in middle-old aged patients / 中国骨伤

OBJECTIVE@#To compare the mid-term clinical effect of arthroscopic surgery versus conservative treatment on the middle aged early knee osteoarthritis (EKOA) patients, with the hope to provide clinical evidence for their individual therapy.@*METHODS@#A total of 145 middle aged EKOA patients(182 knees) who received arthroscopic surgery or conservative treatment from January 2015 to December 2016 were retrospectively enrolled, including 35 males and 110 females, aged from 47 to 79 years old with an average of (57.6±6.9) years old, and the duration of disease ranged from 6 to 48 months with an average of(14.6±8.9) months. According to treatment method, patients were divided into arthroscopic surgery group (47 patients, 58 knees) and conservative treatment group(98 patients, 124 knees). Before treatment, patients presented with symptoms of knee joint, such as pain, swelling, locking, limited flexion and extension, and weakness, as well as abnormal findings in knee X-ray (without or suspicious joint space narrow, and a few of osteophyte formation) or in knee MRI (injury or degeneration of articular cartilage or meniscus, loose body in the joint cavity and synovial hyperemia edema, etc). Related data were collected, including duration of knee symptoms, presence of meniscus injury, loose body in the joint cavity or mechanical symptoms such as locking, and visual analogue scale (VAS) and Lysholm knee function score before treatment and at the latest follow-up. Statistical analysis was performed to compare the differences in VAS or Lyshilm score before or after treatment between the low groups and within each group.@*RESULTS@#Patients in the two groups were followed up from 60 to 76 months. In the arthroscopic surgery group, the incision healing was good and no surgical complications occurred. There were no significant differences in age, gender, BMI and follow-up time between the two groups(P>0.05). Before treatment, compared with conservative group, duration of symptoms in the arthroscopic group was longer (P<0.001), comorbidity rates of meniscus injury (P<0.001), free body (P=0.001) and mechanical symptoms (P<0.001) were higher, VAS (P<0.001) and Lysholm score (P<0.001) were worse. At the final follow-up, VAS and Lysholm score in either the conservative group or the arthroscopic group were significantly better than before treatment (P<0.05), while no significant differences between the two groups were found. The VAS was (1.5±1.2) scores in the arthroscopic group and (1.6±1.0)scores in the conservative group(P=0.549), and the Lysholm score was (84.9±12.5) scores in the arthroscopic group and (84.2±9.9) scores in the conservative group (P=0.676).@*CONCLUSION@#Both arthroscopic surgery and conservative treatment have satisfactory intermediate clinical effect middle- aged patients with EKOA, without statistically differences. However, most of the patients before surgery in the arthroscopic treatment group had mechanical locking symptoms caused by meniscus injury or loose body. Therefore, for the middle-aged EKOA patients with mechanical locking symptoms or without obtaining satisfactory outcome after conservative treatment, arthroscopic surgery may be considered.

Correlation of extracellular enzymes activity of Candida glabrata clinical isolates with in vivo pathogenicity in Galleria mellonella larvae / 中华预防医学杂志

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC50) was calculated by using 1.25×108 CFU/ml,2.50×108 CFU/ml,3.75×108 CFU/ml,5.00×108 CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC50 concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC50=2.5×108 CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Qualitative and quantitative study of flavonoids in Notoginseng Radix et Rhizoma based on UPLC-Q-TOF-MS and HPLC-DAD / 中国中药杂志

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-β-D-xylosyl)-β-D-galactoside was the highest with the average content in the tested samples of 161.0 μg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 μg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 μg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.

Contrast-enhanced ultrasound and contrast-enhanced computed tomography for differentiating mass-forming pancreatitis from pancreatic ductal adenocarcinoma: a meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Patients with mass-forming pancreatitis (MFP) or pancreatic ductal adenocarcinoma (PDAC) presented similar clinical symptoms, but required different treatment approaches and had different survival outcomes. This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) in differentiating MFP from PDAC.@*METHODS@#A literature search was performed in the PubMed, EMBASE (Ovid), Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Weipu (VIP), and WanFang databases to identify original studies published from inception to August 20, 2021. Studies reporting the diagnostic performances of CEUS and CECT for differentiating MFP from PDAC were included. The meta-analysis was performed with Stata 15.0 software. The outcomes included the pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CEUS and CECT. Meta-regression was conducted to investigate heterogeneity. Bayesian network meta-analysis was conducted to indirectly compare the overall diagnostic performance.@*RESULTS@#Twenty-six studies with 2115 pancreatic masses were included. The pooled sensitivity and specificity of CEUS for MFP were 82% (95% confidence interval [CI], 73%-88%; I2  = 0.00%) and 95% (95% CI, 90%-97%; I2  = 63.44%), respectively; the overall +LR, -LR, and DOR values were 15.12 (95% CI, 7.61-30.01), 0.19 (95% CI, 0.13-0.29), and 78.91 (95% CI, 30.94-201.27), respectively; and the area under the SROC curve (AUC) was 0.90 (95% CI, 0.87-92). However, the overall sensitivity and specificity of CECT were 81% (95% CI, 75-85%; I2  = 66.37%) and 94% (95% CI, 90-96%; I2  = 74.87%); the overall +LR, -LR, and DOR values were 12.91 (95% CI, 7.86-21.20), 0.21 (95% CI, 0.16-0.27), and 62.53 (95% CI, 34.45-113.51), respectively; and, the SROC AUC was 0.92 (95% CI, 0.90-0.94). The overall diagnostic accuracy of CEUS was comparable to that of CECT for the differential diagnosis of MFP and PDAC (relative DOR 1.26, 95% CI [0.42-3.83], P  > 0.05).@*CONCLUSIONS@#CEUS and CECT have comparable diagnostic performance for differentiating MFP from PDAC, and should be considered as mutually complementary diagnostic tools for suspected focal pancreatic lesions.