[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Growth hormone supplementation during ovarian stimulation in women with advanced maternal age undergoing preimplantation genetic testing for Aneuploidy.

BACKGROUND: Studies have shown that supplementation with recombinant human GH (rh-GH) during ovarian stimulation (OS) may improve the ovarian response and clinical outcomes of IVF. However, it remains unclear whether GH is associated with the ploidy status of embryos, and therefore, is unable to explain the underlying reason for the effect of GH on IVF outcomes. This study aimed to investigate whether GH supplementation in women with advanced maternal age (AMA) during OS is related to an increased probability of obtaining euploid blastocysts. METHODS: This was a single center retrospective cohort study. The data of all women aged 38-46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle between January 2021 and June 2022 were reviewed. Patients in the GH group received 4 IU/day subcutaneous GH supplementation from the beginning of OS to the trigger day, and patients in the control group did not. A total of 140 patients in the GH group and 272 patients in the control group were included after 1:2 propensity score matching. RESULTS: The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group than that in the control group (41.43% vs. 27.21%, P = 0.00). The GH group had a significantly higher euploid blastocyst rate per cohort (32.47% vs. 21.34%, P = 0.00) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.35 ± 0.40 vs. 0.21 ± 0.33, P = 0.00; per OS cycle 0.27 ± 0.38 vs. 0.16 ± 0.30, P = 0.02). However, the benefit of GH was more significant in patients aged 38-40 years, but not significant in patients aged 41-46 years. Pregnancy outcomes were similar between the two groups after embryo transfer. CONCLUSIONS: GH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38-40 years, but this benefit is not significant in women aged 41-46 years. Our results explained the underlying reason for the effect of GH on IVF outcomes in existing studies, and might be helpful for AMA patients undergoing PGT-A cycles to obtain a better outcome meanwhile to avoid over-treatment. TRIAL REGISTRATION: NCT05574894, www. CLINICALTRIALS: gov .

Hyperbaric oxygen therapy: a possible choice for patients with resistant thin endometrium during frozen embryo transfer treatments.

BACKGROUND: Thin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments. METHODS: This prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(< 7 mm) on the endometrium transformation day, despite the use of standard therapies as well as adjuvant therapies, were enrolled in the study. Patients were assigned voluntarily to either the HBOT group or the concurrent control group. The HBOT group received daily HBOT for at least 10 days during the proliferative phase, in addition to the routine endometrium preparation methods and the concurrent control group underwent cycles without HBOT. Propensity score matching (PSM) was used to ensure comparability between the groups. Both self-control and case-control comparisons were conducted. The primary outcome measured was endometrial thickness (ET) on the day of endometrium transformation. Secondary outcomes included intrauterine pregnancy rate (IPR), embryo implantation rate (IR), miscarriage rate, and others. RESULTS: Patients in the HBOT group demonstrated a significantly thicker endometrial thickness on the day of endometrium transformation after undergoing therapy (5.76 ± 1.66 vs. 6.57 ± 1.23, P = 0.002). This improvement was accompanied by a decreased rate of cycle cancellations. Baseline parameters and endometrial thickness were comparable between the HBOT group and the concurrent control group during the cycle. The IPR was similar in patients who received cleavage-stage embryos (0.0% vs. 6.7%, P = 1.00), but significantly higher in patients in the HBOT group who received blastocysts (53.8% vs. 18.2%, P = 0.017). CONCLUSIONS: A period of HBOT prior to endometrium transformation contributes to increased endometrial thickness and facilitates blastocyst implantation in patients with resistant thin endometrium during FET treatments. TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry (registration no. ChiCTR2300072831, retrospectively registered).

Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation.

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 µmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Genipin Attenuates Sepsis-Induced Splenocyte Apoptosis via the Inhibition of Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.

Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose.

Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

Effect of tea polyphenols on sturgeon myofibrillar protein structure in the in vitro anti-glycation model mediated by low temperature vacuum heating.

The binding mechanism between tea polyphenols and sturgeon myofibrillar protein (SMP) in the early stage (0, 2, 4 min), middle stage (6, 10 min) and late stage (15 min) of low temperature vacuum heating (LTVH) in an in vitro anti-glycation model was investigated. The result indicated that the protein cross-linking during LTVH treatment were mainly induced by tea polyphenols. The loss rate of free arginine (Arg) and free lysine (Lys) of SMP at the late stage of LTVH treatment (15 min) was 73.95 % and 83.16 %, respectively. The hydrophobic force and disulfide bond were the main force between tea polyphenols and SMP in the middle and late stage of LTVH treatment. The benzene ring and phenolic hydroxyl group of tea polyphenols can interact with the amino acid residues of SMP, which was exothermic and entropy-increasing. This study provides new insights in the interaction mechanisms between tea polyphenols-protein during heat treatment process.

Effect of tea polyphenols supplement on growth performance, antioxidation, and gut microbiota in squabs.

Early life nutritional supplementation can significantly improve pigeon health. Both the nutritional crops of parental pigeons and the intestinal development of squabs play key roles in the growth rate of squabs. Tea polyphenols (TPs), as natural plant extracts, exhibit potential biological activities. However, the impact of TPs on the intestinal function of squabs is not known. This study evaluated the effects of TPs on growth performance, immunity, antioxidation, and intestinal function in squabs. A total of 432 young pigeons (1 day old) were divided into four groups: a control group (fed a basic diet) and three treatment groups (low, medium, and high dose groups; 100, 200, and 400 mg/kg TPs, respectively). On the 28th day, samples of serum, mucosal tissue, and digests from the ileum of squabs were collected for analysis. The results revealed that TP supplementation significantly reduced the feed-to-meat ratio and improved the feed utilization rate and serum biochemical indices in squabs. Additionally, it enhanced the intestinal barrier function of birds by promoting intestinal development and integrity of tight junctions and regulating digestive enzyme activities and intestinal flora. Mechanistically, TPs activated the Nrf2-ARE signaling pathway, which may be associated with improved antioxidant and immune responses, correlating with an increased abundance of Candida arthritis and Corynebacterium in the ileum.

Hyperpigmentation Inhibits Early Skeletal Muscle Development in Tengchong Snow Chicken Breed.

Tengchong snow, which has white feathers and black meat, is one of the most important black-bone chicken breeds and a genetic treasure of black food in China. Although the black meat traits are dominant, there are some chickens with white meat traits born in the process of folk selection and breeding. The purpose of this study was to compare the differences in skeletal muscle development between Tengchong snow black meat chickens (BS) and white meat chickens (WS), as well as whether excessive melanin deposition has an effect on skeletal muscle development. The BS and WS groups were selected to determine their muscle development difference at stages of 1, 7, 14, 21, and 42 days, using histological stain methods to analyze the development and composing type of breast and leg muscle fibers, as well as the count of melanin in BS muscle fibers. Finally, we were validated key candidate genes associated with muscle development and melanin synthesis. The results showed that BS breast muscle development was inhibited at 7, 14, and 21 days, while the leg muscle was inhibited at 7, 14, 21, and 42 days, compared to WS. Melanin deposition was present in a temporal migration pattern and was greater in the leg muscles than in the breast muscles, and it focused around blood vessels, as well as the epithelium, perimysium, endomysium, and connective tissue. Additionally, melanin produced an inhibitory effect similar to MSTN during skeletal muscle fiber development, and the inhibition was strongest at the stage of melanin entry between muscle fibers, but the precise mechanisms need to be confirmed. This study revealed that melanin has an inhibitory effect on the early development of skeletal muscle, which will provide new insights into the role of melanin in the black-boned chicken and theoretical references for the future conservation and utilization of black-boned chicken.

Somatostatin plus Gastroscopic Administration of Omeprazole for the Treatment of Acute Upper Gastrointestinal Bleeding: An Exploration of a Promising Alternative.

Objective: To analyze the efficacy and safety of somatostatin combined with gastroscopic administration of omeprazole in the treatment of acute upper gastrointestinal bleeding. Methods: Eligible 112 patients with acute upper gastrointestinal bleeding treated in our hospital from May 2019 to July 2020 were randomized at a ratio of 1 : 1 either to the control group (somatostatin) or observation group (somatostatin combined with omeprazole gastroscope administration). The treatment efficacy, the average hemostasis time, rebleeding rate, average length of hospital stay, and the incidence of adverse reactions were compared. Results: The study group demonstrated significantly higher total effective rate than the control group (96.45% vs. 80.36%, <0.05). The study group demonstrated superior performances compared to the control group with respect to the average hemostasis time ((14.17 ± 2.53 h) vs. (28.84 ± 4.07 h)), rebleeding rate (3.57% vs. 14.28%), and average length of hospital stay ((5.86 ± 1.26 d) vs. (9.74 ± 1.07 d)) (all p < 0.05). The chi-square test revealed a remarkably lower total incidence of adverse reactions in the study group vs. control group which was (4 (7.14%) vs. 12 (21.43%)) (p < 0.05). Conclusion: The combination of somatostatin and gastroscopic administration of omeprazole might be a promising alternative for the treatment of acute upper gastrointestinal bleeding. It improves the clinical treatment effect and controls the symptoms of patients, with a good safety profile.

Ma's bamboo-based medicinal moxibustion therapy of low back pain in lumbar disc herniation: study protocol for a randomized controlled trial.

BACKGROUND: Lumbar disc herniation (LDH) is a common and frequently occurring disease in clinics. Low back pain and sciatica are the presenting symptoms of LDH. To some extent, it can be considered that measures with the capability to improve low back pain or sciatica have the potential to treat LDH. Ma's bamboo-based medicinal moxibustion therapy can effectively reduce the degree of low back pain and has been widely used. Studies of small sample size have seen significant improvement on pain relief. The aim of this trial is to evaluate the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy in the treatment of LDH low back pain. METHODS/DESIGN: The trial is a multicenter, randomized, parallel-group, non-inferiority study. Three hundred and twelve patients will be randomly assigned to a Ma's bamboo-based medicinal moxibustion group (n=156) and an acupuncture group (n=156). Patients in each group will receive treatment every day, 6 times a week, 12 times in total. Follow-up will be conducted 14 days after treatment. The primary outcome will be the visual analog scale(VAS) at baseline, after 6 times of treatment, end of treatment, and follow-up. The secondary outcomes will include Oswestry disability indexes (ODI), modified Japanese Orthopaedic Association low back pain (M-JOA) score, serum ß-endorphin (ß-EP), and serum substance P (SP). ß-EP and SP, as well as safety evaluation indexes (routine blood, liver, and kidney function and electrocardiogram), will be measure at baseline and after the end of treatment. The number, nature, and severity of adverse events will be recorded. DISCUSSION: The results of the trial will compare the efficacy of low back pain in LDH between Ma's bamboo-based medicinal moxibustion group and the acupuncture group and will be expected to make a systematic and objective evaluation of the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy. TRIAL REGISTRATION: ChiCTR2000038725 . Registered on 29 September 2020.

Clinical Significance of Albumin- and Bilirubin-Based Biomarkers in Glaucoma: A Retrospective Case-Control Study.

Glaucoma is the second leading cause of global blindness. The etiology of glaucoma is complicated. In addition to elevated intraocular pressure (IOP), several other mechanisms have been implicated in pathogenesis, such as oxidative stress and systemic inflammation. Serum albumin (ALB) and bilirubin (BIL) have been reported to have potent antioxidant properties and contribute to maintain redox homeostasis in various diseases. However, associations between these parameters and glaucoma remain mostly unknown. Here, we conducted a retrospective case-control study, revealing that serum ALB, total BIL (TBIL), and indirect BIL (IBIL) levels were markedly lower in glaucoma patients than those in healthy controls. Furthermore, the neutrophil-to-ALB (NAR), neutrophil-to-TBIL (NTBR), and neutrophil-to-IBIL (NIBR) ratios were greatly higher in glaucoma. Additionally, interestingly, lower ALB and BIL levels and higher NAR, NTBR, and NIBR were associated with severer glaucomatous visual impairment, and NAR, NTBR, and NIBR showed good accuracy as diagnostic tests for glaucoma severity, suggesting these indices might be useful as discriminative biomarkers for disease severity. Our current findings demonstrate associations between ALB, BIL, NAR, NTBR, NIBL, and glaucoma. It might be useful to use NAR, NTBR, and NIBR as predictive markers for disease severity and employ ALB/BIL as alternative therapy or adjuvant medicines in glaucoma patients.

Terrestrosin D ameliorates skin lesions in an imiquimod-induced psoriasis-like murine model by inhibiting the interaction between Substance P and Dendritic cells.

BACKGROUND: Psoriasis is a psychosomatic immune skin disease with psychological factors contributing to the disease. Substance P (SP) is highly expressed in the psoriatic lesions of patients and is involved in pathological disease progression. Tribulus terrestris L. has been used as a Chinese herbal medicine for disease prevention for thousands of years. Terrestrosin D (TED) has been identified as the effective monomeric component of Tribulus terrestris L.. PURPOSE: We investigated whether TED could reverse imiquimod-induced psoriatic lesions, and then, investigated its potential mechanism of action both in vivo and in vitro. METHODS: 5% imiquimod cream was applied onto the backs of mice for 6 days to induce psoriasis-like skin lesions. The psoriatic area and severity index (PASI) was then used for scoring disease severity. Pathological changes and Ki-67 expression levels in skin lesions were measured using hematoxylin and eosin (H&E) and immunofluorescence staining after TED administration. The in vivo and in vitro expression levels of inflammatory cytokines, the ratio of DCs, and SP were measured using ProcartaPlex Mouse Cytokine panels, flow cytometry, and western blotting. Behavioral assessments were determined using the open field and elevated plus-maze (EPM) test. RESULTS: TED decreased PASI scores, epidermal thickness, Ki-67 expression levels, the ratio of DCs in the spleen, and secretion of IL-12p70, IL-18, and TNF-α in imiquimod-induced psoriasis-like murine models. Furthermore, TED increased IL-10 secretion levels, improved behavior, and down-regulated the expression levels of SP. Additionally, TED inhibited the in vitro maturation and activation of SP-induced CD11c+ DCs and the release of IL-12p70 and IL-23. CONCLUSION: TED reduced DCs maturation, down-regulated the expression levels of inflammatory factors, and improved skin lesions and behavior of psoriasis-like murine models by inhibiting the interaction between Substance P and Dendritic cells.

[Mechanism of Astragali Radix-Coptis Rhizoma pair in treating type 2 diabetes mellitus based on network pharmacology].

This study aims to explore the main mechanism of Astragali Radix-Coptis Rhizoma pair(hereinafter referred to as the pair) in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and animal experiment. The main Chinese medicine compound prescriptions for T2 DM were retrieved from CNKI database and the medicinals with high frequency among these prescriptions were screened. The active components in the above medicinals were searched from TCMSP, TCMID, and previous research, targets of the components from SwissTargetPrediction and SEA, and targets for the treatment of T2 DM from DISGENET, TTD, and DrugBank. Thereby, the medicinal-component-disease-target network was constructed with Cytoscape. The targets were input in String database to yield the related proteins and the protein-protein interaction(PPI) network was constructed by Cytoscape. The biological functions of proteins in the PPI network were analyzed by Cluego. Then, high-fat high-sugar diet and 30 mg·kg~(-1) streptozotocin(STZ, intraperitoneal injection, once) were employed to induce T2 DM in rats and the T2 DM rats were classified into the control group, model group, positive drug(metformin) group, and pair group. After one month of administration, the changes of blood glucose and blood lipids [triglyceride(TG), cholesterol(CHO), low density lipoprotein(LDL), high density lipoprotein(HDL)] were detected with biochemical methods and pathological changes of islet and collagen deposition in pancreatic tissue by HE staining and Masson staining, respectively. The result showed that pair can be used for T2 DM treatment. ras-related C3 botulinum toxin substrate 1(RAC1), paraoxonase 1(PON1), beta-galactoside alpha 2,6-sialyltransferase 1(ST6 GAL1), insulin receptor(INSR), sex hormone-binding globulin(SHBG), ileal sodium/bile acid cotransporter(SLC10 A2), endothelin-1 receptor A(EDNRA), peroxisome proliferator-activated receptor A(PPARA), endothelin receptor B(EDNRB), and 5-hydroxytryptamine receptor 2 A(HTR2 A) were the targets of the pair for the treatment of T2 DM. The main biological functions of the pair were regulating the metabolism of blood glucose and li-pids and protecting the cardiovascular system. The fasting blood glucose, and serum TG, CHO, and LDL were higher(P<0.01) and the HDL was lower(P<0.05) in the model group than in the control group on the 7 th, 14 th, and 28 th days. The fas-ting blood glucose and the serum TG, CHO, and LDL decreased(P<0.05) and the serum HDL increased(P<0.05) in the metformin group and the pair group as compared with those in the model group on the 14 th and 28 th days. There were no significant differences in blood glucose, TG, CHO, LDL, and HDL between the metformin group and the pair group. Rats in the model group demonstrated damaged structures of islets and pancreas, obviously increased deposition of collagen in islets and pancreas, and blurred cell boundaries. Metformin and the pair significantly alleviated the damaged structures and collagen deposition. The pair can effectively regulate the disorders of blood glucose and lipid metabolism in T2 DM and protect the structure and functions of pancreas and islets by controlling cardiovascular system, which is worthy of clinical application and can be used for drug development.

The efficacy and safety of fire needle for cervical spondylotic radiculopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Cervical spondylotic radiculopathy (CSR) is one of the most common types of cervical spondylosis, and its treatments are mainly for relieving radicular pain and improving dysfunction. The existing randomized controlled trials (RCTs) suggest that fire needle may be a potential therapy in the treatment of CSR, but there is no evidence-based medical evidence to date. Therefore, this study will systematically evaluate the efficacy and safety of fire needle in the treatment of CSR. METHODS: We will search for 7 electronic databases (PubMed, EMBASE, Cochrane library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Sinomed, and Wanfang Database) and 2 trial registration platforms (ClinicalTrials.gov and Chinese Clinic Trials.gov) to collect eligible studies. The RCTs related to fire needle for CSR and published up to June 30, 2021 will be included, regardless of language. We will consider the visual analogue scale as the primary outcome and the secondary outcome will include cervical range of motion, assessment of muscle strength, neck disability index, the MOS item short from health survey, activities of daily living, total efficiency, and adverse reactions. We will use the standard proposed in Cochrane Handbook 5.1.0 to assess the quality and bias risk of every RCT, and all analyses will be conducted through RevMan software V5.3 (Copenhagen: Nordic Cochrane Center, Cochrane, Collaborative Organization, 2014). RESULTS: This systematic review and meta-analysis will provide a convincing synthesis of existing evidences on the efficacy and safety of fire needle for CSR, and the results will be submitted to a peer-reviewed journal for publication. CONCLUSION: The results of this study will provide high-quality evidence of fire needle in the treatment of CSR for clinical decision-making. INPLASY REGISTRATION NUMBER: INPLASY202170041.

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

Mulberroside A from Cortex Mori Enhanced Gut Integrity in Diabetes.

BACKGROUND: Diabetic endotoxemia has been recognized as one of the hallmarks of type 2 diabetes mellitus (T2DM). Recent findings suggest that gut leak plays a pivotal role in diabetic endotoxemia. Cortex Mori (CM) has been widely applied in China to ameliorate development of T2DM, but its effect on endotoxemia is unknown. METHODS: The study was constructed with two parts: (1) in vivo study of CM on diabetic endotoxemia in db/db mice. Eight C57BL/6 mice were set as normal control; (2) in vitro study of mulberroside A (MBA) from CM on diabetic endotoxemia. Potential mechanism of MBA on ameliorating diabetic endotoxemia was also explored. RESULTS: The present study found that CM water extract decreased levels of blood glucose, ameliorated liver and renal damage in db/db mice, and ameliorated diabetic endotoxemia (p < 0.01). We also found that the water extract enhanced gut integrity and decreased gut inflammatory protein ICAM-1 expression in db/db mice as detected by H&E staining and immunohistochemistry methods. In the in vitro study, MBA decreased levels of MDA and ROS induced by LPS (p < 0.01) and enhanced the integrity of gut epithelial barrier (p < 0.01). CONCLUSIONS: We found that Cortex Mori and its active component mulberroside A could ameliorate diabetic endotoxemia by preserving gut integrity.

Systems Pharmacology Approach and Experiment Evaluation Reveal Multidimensional Treatment Strategy of LiangXueJieDu Formula for Psoriasis.

Clinical studies have demonstrated the anti-psoriatic effect of the LiangXueJieDu (LXJD) herbal formula. However, the systemic mechanism and the targets of the LXJD formula have not yet been elucidated. In the present study, a systems pharmacology approach, metabolomics, and experimental evaluation were employed. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, 144 active compounds with satisfactory pharmacokinetic properties were identified from 12 herbs of LXJD formula using the TCMSP database. These active compounds could be linked to 125 target proteins involved in the pathological processes underlying psoriasis. Then, the networks constituting the active compounds, targets, and diseases were constructed to decipher the pharmacological actions of this formula, indicating its curative effects in psoriasis treatment and related complications. The psoriasis-related pathway comprising several regulatory modules demonstrated the synergistic mechanisms of LXJD formula. Furthermore, the therapeutic effect of LXJD formula was validated in a psoriasis-like mouse model. Consistent with the systems pharmacology analysis, LXJD formula ameliorated IMQ-induced psoriasis-like lesions in mice, inhibited keratinocyte proliferation, improved keratinocyte differentiation, and suppressed the infiltration of CD3+ T cells. Compared to the model group, LXJD formula treatment remarkably reduced the expression of inflammatory cytokines and factors, such as IL-1ß, IL-6, TNF-α, Cox2, and inhibited the phosphorylation of p-P65, p-IқB, p-ERK, p-P38, p-PI3K, p-AKT, indicating that LXJD formula exerts its therapeutic effect by inhibiting the MAPK, PI3K/AKT, and NF-қB signaling pathways. The metabolic changes in the serum of psoriasis patients were evaluated by liquid chromatography coupled with orbitrap mass spectrometry (LC-MS). The LXJD formula improved two perturbed metabolic pathways of glycerophospholipid metabolism and steroid hormone biosynthesis. Overall, this study revealed the complicated anti-psoriatic mechanism of LXJD formula and also offered a reliable strategy to elucidate the complex therapeutic mechanism of this Chinese herbal formula in psoriasis from a holistic perspective.

The efficacy and safety of moxibustion for chronic fatigue syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is not clear. The main purpose of treatment is to improve autoimmune function and relieve fatigue symptoms. Moxibustion is often used to treat diseases caused by low autoimmunity, especially in relieving fatigue symptoms. It is a superior therapy for CFS in traditional Chinese medicine. At present, there is a lack of the high level clinical evidence to support the moxibustion in the treatment of CFS, so this study will systematically review and analyze the currently available randomized controlled trials to evaluate the efficacy and safety of moxibustion in the treatment of CFS. METHODS: We will systematically search PubMed, EMBASE, Cochrane library, Sinomed, CNKI, VIP, and Wanfang Database, ClinicalTrials.gov and Chinese Clinical Trial Registry will also be searched. The time range for the search will be from database activation to March 31, 2021. The randomized controlled trials (RCTs) associated with moxibustion for CFS will be included, regardless of language.We will use the standard proposed in Cochrane Handbook 5.1.0 to assess the bias risk of a single RCT. The main outcome index of the study is Fatigue Assessment Instrument (FAI), secondary outcome indexes will include Fatigue Scale -14 (FS-14), Fatigue Severity Scale (FSS), Pittsburgh sleep quality index (PSQI), natural killer (NK) cells, interleukin- 2 (IL-2), T lymphocyte subsets (CD4+, CD8+), cure rate, total efficiency and adverse reactions. The random effect model meta was used to analyze the effect data of a single RCT. Heterogeneity will be measured by Cochran Q test and I-squared statistics. We will use 2 subgroup analyses to explore the source of heterogeneity. RCTs with high bias risk was excluded and adjustment effect model was used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias included in RCTs will be assessed by funnel plot and Egger test. RESULTS: This study will objectively and comprehensively evaluate the efficacy and safety of randomized controlled trials of moxibustion in the treatment of chronic fatigue syndrome, and the results will be submitted to peer-reviewed journals for publication. CONCLUSION: This systematic review will provide clinicians with the latest high-quality evidence for the use of moxibustion in the treatment of chronic fatigue syndrome. INPLASY REGISTRATION NUMBER: INPLASY202140063.