The association of the severity of Omicron with menstrual and premenstrual syndrome among reproductive age women in China: a cross-sectional study.

This study aimed to investigate changes in menstruation and the association of the severity of Omicron with menstruation after the nationwide outbreak of COVID-19 in China. A cross-sectional study adopted an electronic questionnaire to conduct an anonymous online survey. The survey targeted women of reproductive age who had been infected with SARS-CoV-2, and were menstruating regularly in the six months prior to the infection, and experienced at least one menstrual cycle after the infection. The 737 included participants were divided into mild and severe groups based on the severity of the infection. Deviations in first menstrual cycle post-infection were reported in 46.4% of participants (mild group 40.1% vs. severe group 55.2%, P<0.05). Menstrual changes were predominantly a late menstrual period (mild group 25.3% vs. severe group 30.4%), a shorter duration of menstrual flow (mild group 10.4% vs. severe group 14.7%), and a decrease in menstrual flow volume (mild group 16% vs. severe group 21.6%). Premenstrual syndrome symptoms in a small number of women were worse compared with pre-infection, especially in the severe group. During the second menstrual period after infection, most participants reported their menstrual characteristics had returned to those of pre-infection (mild group 88% vs. severe group 80.2%, P<0.05). In this investigation, SARS-CoV-2 infection had a substantial effect on women's menstrual characteristics, and the changes were mostly transient. Women with more severe COVID-19 symptoms experienced more significant changes. The potential long-term effects of SARS-CoV-2 on female reproductive health require further observation and research.

Cette étude visait à étudier les changements dans la menstruation et l'association entre la gravité d'Omicron et la menstruation après l'épidémie nationale de COVID-19 en Chine. Une étude transversale a adopté un questionnaire électronique pour mener une enquête anonyme en ligne. L'enquête visait les femmes en âge de procréer qui avaient été infectées par le SRAS-CoV-2, qui avaient leurs règles régulièrement au cours des six mois précédant l'infection et qui ont connu au moins un cycle menstruel après l'infection. Les 737 participants inclus ont été divisés en groupes légers et sévères en fonction de la gravité de l'infection. Des écarts dans le premier cycle menstruel post-infection ont été signalés chez 46,4 % des participantes (groupe léger 40,1 % contre groupe sévère 55,2 %, P <0,05). Les changements menstruels étaient principalement une période menstruelle tardive (groupe léger 25,3 % contre groupe sévère 30,4 %), une durée plus courte du flux menstruel (groupe léger 10,4 % contre groupe sévère 14,7 %) et une diminution du volume du flux menstruel (groupe léger). 16 % contre groupe sévère 21,6 %). Les symptômes du syndrome prémenstruel chez un petit nombre de femmes étaient pires que ceux observés avant l'infection, en particulier dans le groupe sévère. Au cours de la deuxième période menstruelle après l'infection, la plupart des participantes ont déclaré que leurs caractéristiques menstruelles étaient revenues à celles d'avant l'infection (groupe léger 88 % contre groupe sévère 80,2 %, P <0,05). Dans cette enquête, l'infection par le SRAS-CoV-2 a eu un effet substantiel sur les caractéristiques menstruelles des femmes, et les changements ont été pour la plupart transitoires. Les femmes présentant des symptômes plus graves de la COVID-19 ont connu des changements plus importants. Les effets potentiels à long terme du SRAS-CoV-2 sur la santé reproductive des femmes nécessitent des observations et des recherches plus approfondies.

HuNoV Non-Structural Protein P22 Induces Maturation of IL-1ß and IL-18 and N-GSDMD-Dependent Pyroptosis through Activating NLRP3 Inflammasome.

Norovirus infection is the leading cause of foodborne gastroenteritis worldwide, causing more than 200,000 deaths each year. As a result of a lack of reproducible and robust in vitro culture systems and suitable animal models for human norovirus (HuNoV) infection, the pathogenesis of HuNoV is still poorly understood. In recent years, human intestinal enteroids (HIEs) have been successfully constructed and demonstrated to be able to support the replication of HuNoV. The NLRP3 inflammasome plays a key role in host innate immune responses by activating caspase1 to facilitate IL-1ß and IL-18 secretion and N-GSDMD-driven apoptosis, while NLRP3 inflammasome overactivation plays an important role in the development of various inflammatory diseases. Here, we found that HuNoV activated enteric stem cell-derived human intestinal enteroids (HIEs) NLRP3 inflammasome, which was confirmed by transfection of Caco2 cells with full-length cDNA clones of HuNoV. Further, we found that HuNoV non-structural protein P22 activated the NLRP3 inflammasome and then matured IL-1ß and IL-18 and processed the cleavage of gasdermin-D (GSDMD) to N-GSDMD, leading to pyroptosis. Besides, berberine (BBR) could ameliorate the pyroptosis caused by HuNoV and P22 by inhibiting NLRP3 inflammasome activation. Together, these results reveal new insights into the mechanisms of inflammation and cell death caused by HuNoV and provide potential treatments.

Effects of lifestyle intervention on adults with metabolic associated fatty liver disease: A systematic review and meta-analysis.

Introduction: This systematic review and meta-analysis evaluates the overall effects of lifestyle interventions upon hepatic fat content and metabolism-related indicators among adults with metabolic associated fatty liver disease. Methods: It was registered under PROSPERO (CRD42021251527). We searched PubMed, EMBASE, MEDLINE, Cochrane, CINAHL, Scopus, CNKI, Wan-fang, VIP, and CBM from the inception of each database to May 2021 for RCT studies of lifestyle interventions on hepatic fat content and metabolism-related indicators. We used Review Manager 5.3 for meta-analysis and used text and detailed tabular summaries when heterogeneity existed. Results: Thirty-four RCT studies with 2652 participants were included. All participants were obesity, 8% of whom also had diabetes, and none was lean or normal weight. Through subgroup analysis, we found low carbohydrate diet, aerobic training and resistance training significantly improved the level of HFC, TG, HDL, HbA1c, and HOMA-IR. Moreover, low carbohydrate diet is more effective in improving HFC than low fat diet and resistance training is better than aerobic training in reduction in HFC and TG (SMD, -0.25, 95% CI, -0.45 to -0.06; SMD, 0.24, 95% CI, 0.03 to 0.44, respectively). Discussion: Overall, this is the first review that systematically synthesizes studies focused on the effects of various lifestyle on adults with MAFLD. The data generated in this systematic review were more applicable to obesity MAFLD rather than lean or normal weight MAFLD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42021251527).

Jatrorrhizine Suppresses Murine-Norovirus-Triggered N-GSDMD-Dependent Pyroptosis in RAW264.7 Macrophages.

Human norovirus (HNV) is one of the emerging and rapidly spreading groups of pathogens and the main cause of epidemic viral gastroenteritis globally. Due to a lack of in vitro culture systems and suitable animal models for HNV infection, murine norovirus (MNV) has become a common model. A recent study showed that MNV activates NLRP3 inflammasome leading to pyroptosis. Jatrorrhizine (JAT) is a natural isoquinoline alkaloid isolated from Coptis Chinensis, which has been proven to have antibacterial, anti-inflammatory, and antitumor effects. However, whether JAT has an effect on norovirus gastroenteritis and the underlying molecular mechanism remain unclear. Here, we found that JAT could ameliorate NLRP3-N-GSDMD-dependent pyroptosis induced by MNV infection through inhibiting the MAPKs/NF-κB signaling pathways and decrease MNV replication in RAW264.7 macrophages, suggesting that JAT has the potential to be a therapeutic agent for treating norovirus gastroenteritis.

Remote pharmacy service in primary care: The implementation of a cloud-based pre-prescription review system.

BACKGROUND: To reduce the occurrence of inappropriate prescription in primary care through the introduction of a cloud-based pre-prescription review system. OBJECTIVE: We aimed to describe the implementation of a cloud-based pre-prescription review system in the pharmacy practice of Chinese community health centers (CHCs), which currently have few qualified pharmacists. PRACTICE DESCRIPTION: The cloud-based pre-prescription review system featured reviews by remote clinical pharmacists and targeted the prevention of inappropriate prescription in primary care. PRACTICE INNOVATION: This study describes the implementation of remote pharmacy at 22 CHCs in Futian District, Shenzhen, China. A pre-prescription system was developed and deployed in the cloud, which is linked to CHCs, and a consortium of qualified clinical pharmacists located in tertiary hospital. All prescriptions were mandatorily reviewed before printing and payment. First, prescriptions were reviewed using cloud-based rational drug use software. Then any detected potentially inappropriate prescriptions were reviewed by the remote pharmacist. The pharmacist consortium also modified review rules to improve efficiency and accuracy. EVALUATION METHODS: The frequency and proportions of potentially inappropriate prescriptions identified by the review software and the remote pharmacist consortium were analyzed descriptively. RESULTS: During the 6-month study period (July 1, 2019-December 31, 2019), 340,117 prescription entries from general practitioners in 22 community health care centers were reviewed. Of these, 6479 (3.0%) unique potential entries were suspended for pharmacist review, of which 3230 (49.9%) needed correction from prescribers in the CHCs. The most common corrections were related to improper administration routes or drug-drug interactions or had no justified indications. CONCLUSION: Inappropriate prescription is not uncommon in CHCs. The cloud-based prescription prereview model proposed in this study can serve as an important tool for the prevention of inappropriate prescription in primary care. The pre-prescription review system also provided opportunities for pharmacists to participate in the enhancement of patient care in primary care.

Removal of Congo red dye from aqueous solution with nickel-based metal-organic framework/graphene oxide composites prepared by ultrasonic wave-assisted ball milling.

Metal-organic frameworks (MOFs) were successfully synthesized by ultrasonic wave-assisted ball milling. In the absence of organic solvent, the coupling effect of ultrasonic wave and mechanical force played an significant role in the synthesis of MOFs. Adsorption of Congo red (CR) was studied in view of adsorption kinetic, isotherm and thermodynamics. The adsorbent was carried out using X-ray diffraction (XRD), thermogravimetric analysis (TGA), N2 adsorption-desorption isotherms, Raman spectroscopy and scanning electron microscope (SEM) methods. It was found that pseudo-second-order kinetic model and Freundlich adsorption isotherm matched well for the adsorption of CR onto nickel-based metal-organic framework/graphene oxide composites (Ni-MOF/GO). The results of the adsorption thermodynamics indicated that the adsorption process was a spontaneous and endothermic process. The adsorption capacity of graphene oxide/metal-organic frameworks (GO/MOFs) for CR reached 2489mg/g, much higher than previous reports. It was demonstrated that an increase in the number of active metal sites can dramatically improve the adsorption capacity of dye. A suitable dry temperature is beneficial for the improvement of adsorption capacity for dye. In this paper, the adsorption results indicated that ultrasonic wave-assisted ball milling has a good prospect for synthesis of MOFs with excellent adsorption performance.

Acupuncture for polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin presents in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture has an impact on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction and fertility. OBJECTIVES: To assess the effectiveness and safety of acupuncture treatment of oligo/anovulatory women with polycystic ovarian syndrome (PCOS). SEARCH METHODS: We identified relevant studies from databases including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, EMBASE, PsycINFO, CNKI and trial registries. The data are current to 19 October 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi- or pseudo-RCTs. Primary outcomes were live birth and ovulation (primary outcomes), and secondary outcomes were clinical pregnancy, restoration of menstruation, multiple pregnancy, miscarriage and adverse events. We assessed the quality of the evidence using GRADE methods. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated Mantel-Haenszel odds ratios (ORs) and mean difference (MD) and 95% confidence intervals (CIs). MAIN RESULTS: We included five RCTs with 413 women. They compared true acupuncture versus sham acupuncture (two RCTs), true acupuncture versus relaxation (one RCT), true acupuncture versus clomiphene (one RCT) and electroacupuncture versus physical exercise (one RCT). Four of the studies were at high risk of bias in at least one domain.No study reported live birth rate. Two studies reported clinical pregnancy and found no evidence of a difference between true acupuncture and sham acupuncture (OR 2.72, 95% CI 0.69 to 10.77, two RCTs, 191 women, very low quality evidence).Three studies reported ovulation. One RCT reported number of women who had three ovulations during three months of treatment but not ovulation rate. One RCT found no evidence of a difference in mean ovulation rate between true and sham acupuncture (MD -0.03, 95% CI -0.14 to 0.08, one RCT, 84 women, very low quality evidence). However, one other RCT reported very low quality evidence to suggest that true acupuncture might be associated with higher ovulation frequency than relaxation (MD 0.35, 95% CI 0.14 to 0.56, one RCT, 28 women).Two studies reported menstrual frequency. One RCT reported true acupuncture reduced days between menstruation more than sham acupuncture (MD 220.35, 95% CI 252.85 to 187.85, 146 women). One RCT reported electroacupuncture increased menstrual frequency more than no intervention (0.37, 95% CI 0.21 to 0.53, 31 women).There was no evidence of a difference between the groups in adverse events. Evidence was very low quality with very wide CIs and very low event rates.Overall evidence was low or very low quality. The main limitations were failure to report important clinical outcomes and very serious imprecision. AUTHORS' CONCLUSIONS: Thus far, only a limited number of RCTs have been reported. At present, there is insufficient evidence to support the use of acupuncture for treatment of ovulation disorders in women with PCOS.

Integrative treatment for low back pain: An exploratory systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Low back pain (LBP) is a common musculoskeletal condition often treated using integrative medicine (IM). Most reviews have focused on a single complementary and alternative medicine (CAM) therapy for LBP rather than evaluating wider integrative approaches. This exploratory systematic review aimed to identify randomized controlled trials (RCTs) and provide evidence on the effectiveness, cost effectiveness and adverse effects of integrative treatment for LBP. METHODS: A literature search was conducted in 12 English and Chinese databases. RCTs evaluating an integrative treatment for musculoskeletal related LBP were included. Reporting, methodological quality and relevant clinical characteristics were assessed and appraised. Metaanalyses were performed for outcomes where trials were sufficiently homogenous. RESULTS: Fifty-six RCTs were identified evaluating integrative treatment for LBP. Although reporting and methodological qualities were poor, meta-analysis showed a favourable effect for integrative treatment over conventional and CAM treatment for back pain and function at 3 months or less follow-up. Two trials investigated costs, reporting £ 5332 per quality adjusted life years with 6 Alexander technique lessons plus exercise at 12 months follow-up; and an increased total costs of $244 when giving an additional up to 15 sessions of CAM package of care at 12 weeks. Sixteen trials mentioned safety; no severe adverse effects were reported. CONCLUSION: Integrative treatment that combines CAM with conventional therapies appeared to have beneficial effects on pain and function. However, evidence is limited due to heterogeneity, the relatively small numbers available for subgroup analyses and the low methodological quality of the included trials. Identification of studies of true IM was not possible due to lack of reporting of the intervention details (registration No. CRD42013003916).

Chinese herbal medicine Guizhi Fuling Formula for treatment of uterine fibroids: a systematic review of randomised clinical trials.

BACKGROUND: Guizhi Fuling Formula is widely applied for uterine fibroids in China. Many clinical trials are reported. This study assessed the efficacy and safety of Guizhi Fuling Formula for the treatment of uterine fibroids. METHODS: PubMed, Cochrane CENTRAL, EMBASE, and four Chinese databases were searched through May 2013. We included randomised controlled trials (RCTs) that tested Guizhi Fuling Formula for uterine fibroids, compared with no intervention, placebo, pharmaceutical medication, or other Chinese patent medicines approved by the State Food and Drug Administration of China. Authors extracted data and assessed the quality independently. We applied RevMan 5.2.0 software to analyse data of included randomised trials. RESULTS: A total of 38 RCTs involving 3816 participants were identified. The methodological quality of the included trials was generally poor. Meta-analyses demonstrated that Guizhi Fuling Formula plus mifepristone were more effective than mifepristone alone in reducing the volume of fibroids (in total volume of multiple fibroids, MD -19.41 cm(3), 95% CI -28.68 to -10.14; in average volume of multiple fibroids, MD -1.00 cm(3), 95% CI -1.23 to -0.76; in average volume of maximum fibroids, MD -3.35 cm(3), 95% CI -4.84 to -1.87, I(2) = 93%, random effects model). Guizhi Fuling Formula significantly improved symptoms of dysmenorrhea either when it was used alone (RR 2.27, 95% CI 1.04 to 4.97) or in combination with mifepristone (RR 2.35, 95% CI 1.15 to 4.82). No serious adverse events were reported. CONCLUSIONS: Guizhi Fuling Formula appears to have additional benefit based on mifepristone treatment in reducing volume of fibroids. However, due to high risk of bias of the trials, we could not draw confirmative conclusions on its benefit. Future clinical trials should be well-designed and avoid the issues that are identified in this study.

Structure of the JmjC-domain-containing protein JMJD5.

The post-translational modification of histone tails is the principal process controlling epigenetic regulation in eukaryotes. The lysine methylation of histones is dynamically regulated by two distinct classes of enzymes: methyltransferases and demethylases. JMJD5, which plays an important role in cell-cycle progression, circadian rhythms and embryonic cell proliferation, has been shown to be a JmjC-domain-containing histone demethylase with enzymatic activity towards H3K36me2. Here, the crystal structure of human JMJD5 lacking the N-terminal 175 amino-acid residues is reported. The structure showed that the Gln275, Trp310 and Trp414 side chains might block the insertion of methylated lysine into the active centre of JMJD5, suppressing the histone demethylase activity of the truncated JMJD5 construct. A comparison of the structure of JMJD5 with that of FIH, a well characterized protein hydroxylase, revealed that human JMJD5 might function as a protein hydroxylase. The interaction between JMJD5 and the core histone octamer proteins indicated that the histone proteins could be potential substrates for JMJD5.

Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes.

Macrophages (Mvarphi) in most solid tumors exhibit a distinct immunosuppressive phenotype, but the mechanisms that allow tumor microenvironments to "educate" Mvarphi are incompletely understood. Here, we report that culture supernatants (TSNs) from several types of tumor cell lines can drive monocytes to become immunosuppressive Mvarphi. Kinetic experiments revealed that soon after exposure to these TSNs, monocytes began to provoke transient proinflammatory responses and then became refractory to subsequent stimulation. Other TSNs that failed to cause such temporary preactivation did not alter Mvarphi polarization. Consistent with these results, we observed that the monocytes/Mvarphi in different areas of human tumor samples exhibited distinct activation patterns. Moreover, we found that hyaluronan fragments constitute a common factor produced by various tumors to induce the formation of immunosuppressive Mvarphi, and also that upregulation of hyaluronan synthase-2 in tumor cells is correlated with the ability of the cells to cause Mvarphi dysfunction. These results indicate that soluble factors derived from tumor cells, including hyaluronan fragments, co-opt the normal development of Mvarphi to dynamically educate the recruited blood monocytes in different niches of a tumor. The malignant cells can thereby avoid initiation of potentially dangerous Mvarphi functions and create favorable conditions for tumor progression.