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This meta-analysis was performed to evaluate the clinical efficacy and safety of Chinese patent medicines in the treatment of subacute thyroiditis (SAT).Chinese databases were searched using a combination of "patent Chinese medicine", "traditional Chinese medicine", "traditional Chinese and western medicine", "sub-thyroiditis", and "subacute thyroiditis". Studies that set Chinese patent medicine treatment of SAT as the experimental group were selected. Then, meta-analysis was performed by RevMan 5.3.A total of 12 studies were included, and most of them had a high risk of bias (low quality). The heterogeneity test results of clinical efficacy showed that Chi2=6.21, df=7, P=0.520.1, and I2=0%50%. Then, the fixed effects model (FEM) was used, with OR =2.80; 95% confidence interval (CI): 1.89-4.13. The heterogeneity test of recurrence rate showed that Chi2=10.69, df=9, P=0.300.1, and I2=16%50%. The heterogeneity test of erythrocyte sedimentation rate showed that I2=97%, P0.00001, MD =-10.02; 95% CI: -12.88 to -7.16, and P0.00001. The heterogeneity test of free triiodothyronine showed that Chi2=500.75, I2=99%50%, P0.00001, MD =-2.88; 95% CI: -3.85 to -1.91; Z=5.83, and P0.00001. The heterogeneity test of free thyroid hormone showed that Chi2=25.15, I2=72%50%, P=0.0007, MD =-2.48; 95% CI: -3.69 to -1.26; Z=3.99, and P0.0001. The heterogeneity test of the occurrence of adverse reactions showed that Chi2=11.28, df=11, P=0.420.1, and I2=3%50%, and the combined effect size was Z=6.49 and P0.00001, with OR =0.21; 95% CI: 0.13-0.34.The meta-analysis of this study confirms that Chinese patent medicines have considerable clinical effects in the treatment of SAT. They can reduce the recurrence rate, adjust the levels of free triiodothyronine and free thyroid hormone, and have good safety.

Panax notoginseng saponins (PNS), the main bioactive constituents of a traditional Chinese herb Panax notoginseng, were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia. The oxygen-glucose-deprived (OGD) model of rat brain microvascular endothelial cells (BMECs) was used in this study. The alteration of gene expression in rat BMECs after PNS treatment was measured by microarray and indicated that there were 38 signaling pathways regulated by PNS. Among them, RIG-I receptor and related signaling molecules TNF receptor-associated factor 2 (Traf2) and nuclear factor-kappa B (NF-κB) were significantly suppressed by PNS, which was verified again in OGD-induced BMECs measured by FQ-PCR and western blotting and in middle cerebral artery occlusion (MCAO) rats measured by immunohistochemistry. The levels of TNF-α, IL-8, and the downstream cytokines regulated by RIG-I receptor pathway were also decreased by PNS. Meanwhile, the neurological evaluation, hematoxylin and eosin (HE) staining, and Evans blue staining were conducted to evaluate the effect of PNS in MCAO rats. Results showed PNS significantly improved functional outcome and cerebral vascular leakage. Flow cytometry showed the number of the inflammatory cells infiltrated in brain tissue was decreased in PNS treatment. Our results identified that RIG-I signaling pathway mediated anti-inflammatory properties of PNS in cerebral ischemia, which provided the novel insights of PNS application in clinics.

Background Group A rotavirus (RVA) is one of the most common causes of severe diarrhea in children worldwide. However, RVA is also an important pathogen causing adult diarrhea, with higher infection rates in older patients. To provide evidence for rotavirus epidemic control and to inform vaccine development, we analyzed the molecular epidemiology of RVA among adult outpatients with diarrhea in Beijing from 2011 to 2018. Materials and methods Stool specimens were collected monthly from 14 districts. RVA was detected using enzyme linked immunosorbent assay and real time reverse transcription polymerase chain reaction (RT-PCR). Genotyping of rotavirus was performed using multiplex semi-nested RT-PCR. Phylogenetic analysis was performed using maximum likelihood methods implemented in MEGA software (version 6.06). Logistic regression and chi-square tests were used to assess differences among age groups, districts, years, and genotype distributions. Results The prevalence of rotavirus was 10.16% (1,310/12,893) among adult outpatients with diarrhea from 2011 to 2018 in Beijing. The highest prevalence (13.74%, 600/4,367) was observed among those aged 41 to 65 years. November, December, and January had the highest positive detection rates. In 2011, G3P[8] and G9P[8] were the dominant genotypes. Starting from 2012, G9P[8] became the dominant genotype. Most G9 strains belonged to the G9-VI clade. Most P[8] strains belonged to the P[8]-III clade. Conclusions RVA is a major cause of adult diarrhea in Beijing. Continuous molecular surveillance is needed, and transmission of rotavirus between children and adults should be investigated further. This article is protected by copyright. All rights reserved.

Weihong Li,1,* Yanrong Wang,1,* Yingzi Pei,2 Yue Xia2 1GCP Office of Cangzhou Central Hospital, Cangzhou, Hebei, 061000, People’s Republic of China; 2Research Center of Beijing Fuyuan Pharmaceutical Co., Ltd. (Formerly Beijing Wansheng Pharmaceutical Co., Ltd.), Beijing, 101113, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihong LiGCP Office of Cangzhou Central Hospital, No. 16 on Xinhua Road, Cangzhou, Hebei, 061000, People’s Republic of ChinaTel +86 18713731395Fax +86 3172072825Email sarry610@163.comPurpose: The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different manufacturers in healthy Chinese volunteers to obtain adequate PK evidence for the registration approval of the test formulation.Patients and Methods: A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR20182362). Eighteen subjects each were selected for a fasted study and a fed study. Eligible participants were randomly assigned in a 1:1 ratio to receive a single dose of the reference formulation or the test formulation, followed by a 5-day washout period and the administration of the alternate formulation. Plasma samples were collected over a 24-hour period following tablet administration and analyzed for montelukast contents by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The PK parameters, such as maximum serum concentration (Cmax), area under the curve (AUC) from t = 0 to the last quantifiable concentration (AUC0–t), AUC from t = 0 to infinity (AUC0–∞), half-life (t1⁄ 2), time to Cmax (Tmax), and terminal elimination rate constant (λz), were evaluated. The safety assessment included changes in vital signs (blood pressure, pulse, and temperature) or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and the incidence of adverse events (AEs).Results: The geometric mean ratios (GMRs) between the two formulations for the primary pharmacokinetic parameters (Cmax, AUC0– 24, and AUC 0–∞) and the corresponding 90% confidence intervals (Cis) were all within the range of 80.00– 125.00% for both the fasting and fed states. The safety profiles for both treatments were comparable.Conclusion: The PK analysis revealed that the test and reference formulations of montelukast sodium chewable tablets were bioequivalent and well-tolerated by healthy Chinese subjects.Keywords: montelukast sodium, bioequivalence, pharmacokinetic profile, HPLC-MS/MS, adverse events

Objective: To determine the effect of gut microbiota on a rat model of post-traumatic stress disorder (PTSD) and explore the correlation of gut microbiota with behavior and neurotransmitters. Methods: We established a single prolonged stress (SPS) model to examine the pathogenesis of PTSD on rat behavior, gut microbiota, and neurotransmitter levels. Rats were separated into control and model groups, and neurotransmitter levels were measured using enzyme linked immunosorbent assay. Then, 16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups. Results: Compared with those in the control group, freezing time significantly increased, while number of standing upright, crossing frequency, time spent in the central arena, and total distance traveled were significantly reduced in the model group after exposure to SPS (all P

The tooth-marked tongue refers to the tongue with the edge featured in jagged teeth marks, which is a significant indicator for reflecting the conditions of patients' internal organs in Traditional Chinese Medicine (TCM). From the perspective of computer vision, due to the small variance in the global region (original image) but the large variance in the local region (tongue region), especially in the differential region (tongue edge region around landmarks), the recognition of the tooth-marked tongue is a naturally fine-grained classification task. To address this challenging task, a two-stage method based on tongue region detection and tongue landmark detection via deep learning is proposed in this paper. In the first stage, we introduce a cascaded convolutional neural network to detect the tongue region and tongue landmarks simultaneously for minimizing the redundancy information and maximizing discriminative information explicitly. In the second stage, we send not only the detected tongue region but also the detected tongue landmarks to a fine-grained classification network for the final recognition. Conclusively, our method is highly consistent with human perception. Moreover, to the best of our knowledge, we are the first attempt to manage the tooth-marked tongue recognition via deep learning. We conducted extensive experiments with the proposed method. The experimental results demonstrate the effectiveness of the proposed method.

Background: Rapid and accurate high-throughput estimation of radiation dose aims to help medical rescue in nuclear radiation accident. However, current methods of dose estimation are still lacking of speedy or accuracy. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Methods: Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The radiation sensitivity and baseline levels of candidate genes were verified. The approximate threshold for guiding medical treatment was estimated for each gene, and four genes were combined to construct an effectively early dose estimation model of radiation.Results: Four p53-related genes, DDB2, AEN, TRIAP1 and TRAF4, were screened and verified their significant radiosensitivity. Their expressions were stable without gender or age difference in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2h-24h after irradiation. Further studies showed these genes can be used as indicators for early medical treatment in acute radiation injury. The effective combination of the four genes could achieve a more accurate dose assessment and injury classification for large-scale wounded patients within 24 hours post exposure.Conclusions: This is the first time to investigate the potential biomarkers of ionizing radiation by systematic study. The effective combination of the four genes provides a new model for dose estimation and injury classification of a large number of exposed population in acute nuclear accidents, and also provides a new idea and method.

Background Insomnia is very common in current society, and patients are often accompanied by a certain degree of anxiety, depression, etc. Recent studies have found that the hypothalamic-pituitary-adrenal (HPA) axis excitement-inhibition state is an important indicator of sleep quality. Wrist-ankle acupuncture (WAA) is safe and effective for insomnia. Based on WAA theory, the acupressure wrist-ankle straps are portable WAA point compression straps that can treat diseases by automatically applying pressure to the treatment location and being operated by patients themselves. We design this trial to evaluate the clinical effect of the acupressure wrist-ankle strap in the treatment of mild insomnia patients with anxiety disorders. Methods/design This trial is a parallel-design, patients-assessor blinded, randomized, sham-controlled. In total, 114 patients diagnosed with mild insomnia and anxiety disorders will be randomly assigned into two groups, the acupressure wrist-ankle strap group or the non-acupressure wrist-ankle strap group; they will receive treatments for eight weeks with five sessions each week. Rating scales, sleep monitors, and laboratory tests will be used to observe the clinical effect. From the perspective of the circadian secretion of peripheral blood-related hormones in the hypothalamic-pituitary-adrenal (HPA) axis, the possible mechanism of acupressure wrist-ankle straps for treating insomnia is studied. Discussion The results of this study will confirm the efficacy of acupressure wrist-ankle strap in treating mild insomnia patients with anxiety disorder and whether its mechanism is related to the HPA axis. The acupressure wrist-ankle strap may become a pure physical, no side effect treatment of mild insomnia. Trial registration Chinese Clinical Trial Registry ChiCTR2000039352. Registered on 24 October 2020.

Background. Many associations between tongue fur and different physiological and biochemical indexes have been revealed. However, the relationship between tongue fur and tumor markers remains unexplored. Methods. We collected the medical examination reports of 1625 participants. Participants were residents of Chengdu, China, undergoing routine health checkups at the health management center of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. The participants’ tongue fur thickness was measured using the DAOSH four-diagnostic instrument. Tumor marker levels, including t-PSA, AFP, CEA, CA125, and CA199, were measured in the clinical laboratory. Curve-fitting and multivariable logistic regression were used to analyze the association between tongue fur thickness and tumor marker abnormality. Results. Curve-fitting showed that the relationship between tongue fur thickness and abnormal tumor marker rate was nonlinear, similar to a U shape. As the tongue fur thickness value increased, the abnormal tumor marker probability initially decreased and then increased. Logistic regression showed that, in the crude model, compared with the thin tongue fur group, the odds ratios (ORs) and 95% confidence intervals (CIs) of the less or peeling tongue fur group and thick tongue fur group for tumor marker abnormality were 1.79 (1.02–3.17) and 1.70 (1.13–2.54), respectively. After adjusting gender, age, body mass index (BMI), smoking history, drinking history, tongue color, the form of the tongue, and fur color, the ORs and 95% CIs of the less or peeling tongue fur group and thick tongue fur group were 1.93 (1.04–3.57) and 1.82 (1.17–2.81), respectively. Conclusions. Excessive or very little tongue fur is associated with tumor marker abnormality. Further cross-sectional studies are needed to evaluate the clinical value of tongue fur for cancer diagnosis and screening.

The Tarim River Basin in Xinjiang, China, has a typical desert riparian forest ecosystem. Analysis of the resilience of this type of ecosystem under extreme drought conditions and ecological rehabilitation projects could provide a theoretical basis for understanding ecosystem stability and resistance, and provide new ecological rehabilitation measures to improve ecosystem resilience. We employed a quantitative framework to assess net primary productivity (NPP) resilience, emphasizing four aspects of NPP dynamics: NPP, NPP stability, NPP resistance, and maximum NPP potential. We compared ecosystem resilience across four time periods: before the implementation of ecological rehabilitation projects (1990–2000), during construction and partial implementation of ecological rehabilitation projects (2001–2012), during the initial project stage of ecological rehabilitation (2013–2015), and during the late project stage of ecological rehabilitation (2016–2018). There are three main finding of this research. (1) Mean NPP was increased significantly from 2013 and was decreased from 2016, especially in the main stream of the Tarim River and in the basins of eight of its nine tributary rivers. (2) Ecosystem resilience in 2013–2018 was greater than in 1990–2012, with the greatest NPP stability, mean NPP and NPP resistance, especially in part one of the river basin (the Aksu River, the Weigan-Kuche River, the Dina River, the Kaidu-Konqi River, and the main stream of the Tarim River). Ecosystem resilience in 2001–2012 was lowest when compared to 1990–2000 and 2013–2018, with lowest mean NPP, NPP stability, NPP resistance and maximum NPP potential, particularly in part two of the river basin (the Kashigr River, the Yarkand River and the Hotan River basins). Therefore, part one was most affected by ecological restoration projects. When 2013–2018 was divided into two distinct stages, 2013–2015 and 2016–2018, resilience in the latter stage was the lowest, with lowest mean NPP, NPP resistance and maximum NPP potential, especially in the main stream of the Tarim River. This may be due to unreasonable water conveyance in 2014–2015. (3) Ecological resilience has increased significantly in 2013–2015 after the implementation of ecological water transfer projects, river regulation, and natural vegetation enclosure projects. Ecosystem resilience could continue to increase even more in the future with the continued implementation of reasonable ecological water transfer projects.

Background: Insomnia is very common in current society, and patients are often accompanied by a certain degree of anxiety, depression, etc. Recent studies have found that the hypothalamic-pituitary-adrenal (HPA) axis excitement-inhibition state is an important indicator of sleep quality. Wrist-ankle acupuncture (WAA) is safe and effective for insomnia. The acupressure wrist-ankle straps, based on WAA theory, is a portable WAA point compression strap, which can treat diseases by automatically applying pressure to the treatment location and be operated by patients themselves. We design this trial to evaluate the clinical effect of the acupressure wrist-ankle strap in the treatment of mild insomnia patients with anxiety disorders. Methods/design: This trial is a parallel-design, patients-assessor blinded, randomized, sham-controlled. In total, 108 patients diagnosed with mild insomnia patients with anxiety disorders will be randomly equally assigned into two groups, acupressure wrist-ankle strap group or non-acupressure wrist-ankle strap group; they will receive treatments for 8 weeks with 5 sessions each week. Rating scales, sleep monitor and laboratory tests will be used to observe the clinical effect. From the perspective of the circadian secretion of peripheral blood-related hormones in the hypothalamic- pituitary- adrenal (HPA) axis, the possible mechanism of acupressure wrist-ankle straps for treating insomnia is studied.Discussion: The results of this study will confirm the efficacy of acupressure wrist-ankle strap combined with CBTI in the treatment of mild insomnia patients with anxiety disorder and whether its mechanism is related to HPA axis. The acupressure wrist-ankle strap may become a pure physical, no side effect treatment of mild insomnia.Trial registration: Chinese Clinical Trial Registry (identifier: ChiCTR2000039352; registration date: 24 October 2020).

Background: From the traditional Chinese medicine (TCM) constitution theory perspective, the phlegm-dampness constitution is thought to be closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). However, this viewpoint still lacks rigorous statistical evidence. This study aimed to test the association between the phlegm-dampness constitution and NAFLD.Methods: We conducted a cross-sectional study. Participants were residents living in Chengdu, China, undergoing health checkups at the health management center of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. TCM constitution type was diagnosed by DAOSH four examinations instrument, NAFLD was diagnosed according to the liver ultrasonography and medical history. Multivariate logistic regression and propensity score matching (PSM) were used to analyze a total of 1,677 qualified data.Results: 1,037 participants had biased constitution(s), 67.8% of which had mixed constitutions (with at least two constitutions). Among 1,677 participants, the phlegm-dampness constitution was associated with the yang-deficiency, yin-deficiency, dampness-heat, qi-depression, and blood-stasis constitutions. The correlation coefficients were 0.11, 0.32, 0.42, 0.20, 0.14, respectively. Between the phlegm-dampness constitution and NAFLD, the odds ratio (OR) and the 95% confidence interval (CI) was 2.05 (1.57–2.69) in the crude model. After adjusting for age, gender, Body mass index (BMI), other biased constitutions, smoking, high blood pressure, diabetes, and dyslipidemia, the OR reduced to 1.51 (1.04–2.18). The associations of seven other biased TCM constitutions and NAFLD were not statistically significant in the fully adjusted model. The PSM analysis showed consistent results with the logistic regression.Conclusions: Among eight biased TCM constitutions, the phlegm-dampness constitution is independently associated with NAFLD. We speculate the phlegm-dampness constitution is a risk factor of NAFLD. Longitudinal studies are needed to confirm this causal relationship in the future. In addition, inconsistent with some TCM practitioners' experience, we disagree that the blood-stasis constitution is associated with NAFLD.

ObjectiveCinnamon is a cooking spice and a medicinal herb. It is increasingly used as a health supplement due to its perceived benefit to prevent and or manage type 2 diabetes and metabolic disorders. However, it is unclear if regular consumption of this medicinal plant will interfere with normal physiological functions. Therefore, this study investigated the impact of daily cinnamon supplements on glucose and lipid metabolic profiles in healthy rats.MethodsMale rats (Sprague Dawley, 8 weeks) were supplied with cinnamon in their diet (equivalent to ∼1 g/day in humans) for two weeks. Blood glucose and lipid levels, as well as metabolic markers in both liver and abdominal white adipose tissue, were measured.ResultsCinnamon significantly increased fat mass and blood cholesterol and low-density lipoprotein (LDL) levels, but reduced fasting blood glucose level by 12%. Liver functional enzymes were normal in rats consuming cinnamon. However, several lipid metabolic markers were impaired which may contribute to dyslipidemia, including two main switches for energy metabolism (sirtuin 1 and peroxisome proliferator-activated receptor-gamma coactivator-1α) and the LDL receptor. However, de novo lipid synthesis enzymes and inflammatory markers were also reduced in the liver by cinnamon treatment, which may potentially prevent the development of steatosis. Markers for lipid oxidation were downregulated in fat tissue in cinnamon-treated rats, contributing to increased fat accumulation.ConclusionDaily low-dose cinnamon supplementation seems to promote abdominal adipose tissue accumulation and disturb lipid homeostasis in healthy rats, raising the concerns regarding daily use in healthy people.

Objectives Noroviruses are a leading cause of acute gastroenteritis (AGE) outbreaks worldwide. This study examined the epidemiology and genetic characteristics of norovirus outbreaks in Beijing, China. Methods Epidemiological data and fecal specimens were collected through the AGE outbreak surveillance system in Beijing. GI and GII genogroup noroviruses were detected and genotyped. The data were analyzed using descriptive statistics. Results Between September 2014 and August 2017, 762 AGE outbreaks were reported in Beijing, of which 661 (86.7%) were laboratory-confirmed as norovirus. Most norovirus outbreaks were reported during the spring (66.9%, 442/661), occurred in kindergartens and elementary schools (92.3%, 610/661), and were caused by GII genogroup noroviruses (95.6%; 632/661). The genotypes of the norovirus strains were determined in 468 outbreaks, and GII.P16-GII.2 and GII.P17-GII.17 strains were the most commonly identified. GII.P17-GII.17 and GII.P16-GII.2 strains predominated in 2014–2015 and 2016–2017 outbreaks, respectively. GII.P16-GII.2 noroviruses were responsible for a steep increase in AGE outbreaks in Beijing: 549 norovirus outbreaks were reported from 2016 to 2017, 9.2 times the number that occurred during the previous year. Conclusions Norovirus causes a large disease burden in Beijing, and the prevalence of non-GII.4 noroviruses presents a new challenge for the development of vaccines.

Cutaneous malignant melanoma (CMM) ranks the most lethal skin cancer worldwide. However, other risk factors have been hardly explored, aside from ultraviolet radiation (UVR). Polychlorinated biphenyls (PCBs) were implied to be potential risk factors for CMM, although all the evidence was obtained from the western countries. This study examined the relationships between plasma levels of PCBs and CMM risk adjusting for sun sensitivity and sun exposure in a Chinese population, using a case-control study, including 450 CMM cases and 500 healthy controls. Plasma levels of a total of 33 PCB congeners were assayed in both cases and controls. Our results showed that there was a significant association between total summed PCB level and CMM risk, with a 1.44-fold increased risk for those in the highest quartile compared to those in the lowest quartile (OR = 1.44, 95% CI: 1.02–2.03, P for trend = 0.031). Significantly increased ORs were also observed for individual PCB congeners (PCB52, PCB170 and PCB180). These associations persisted after control for sun sensitivity and sun exposure. Our study represents the first evidence conducted in Asians, and does support the hypothesis that PCB exposure increases CMM risk. Keywords: Polychlorinated biphenyls, Cutaneous malignant melanoma, Plasma, Case-control study

Objective: To illustrate the effect of geniposide (GP) and panax notoginseng saponins (PNS) on estrogen receptors (ER) including ERα and ERβ within the cytoplasm and nucleus of SH-SY5Y cells. Methods: Immunofluorescence was used to observe the distribution of ERα and ERβ in cytoplasm and nucleus, but Western blot was only for ERβ detection. q-PCR was applied to detect NR3C1, S100A6 and LGALS1downstream mRNA gene expression levels of ER. Results: Through analyzing fluorescence intensity under the administration of GP and PNS in SH-SY5Y cells, we found that the distribution of ERα has not been affected. We also discovered that GP and/or PNS significantly stimulated the transportation of ERβ into the nucleus in a time-dependent manner (all P

Background Physical activity is an important part of the diabetes management plan. However, the effects caused by different training durations and styles of Tai Chi have not been evaluated. We conducted an updated systematic review of the effects of Tai Chi on patients with type 2 diabetes based on different training durations and styles. Methods We performed a search for Chinese and English studies in 8 databases. Two reviewers independently selected the eligible trials and conducted a critical appraisal of the methodological quality. Results Seventeen trials were included. Tai Chi was found to have reduced fasting blood glucose (FBG) [SMD = − 0.54, 95% CI (− 0.91, − 0.16), P = 0.005] and HbA1c [SMD = − 0.68, 95% CI (− 1.17, − 0.19), P = 0.006] overall, compared with a control group. Considering the subgroup analysis, the pooled results showed that 24 movements or Yang-style Tai Chi did not significantly reduce FBG after a duration of ≤3 months [SMD = − 0.46, 95% CI (− 1.42, 0.50), P = 0.35] or > 3 months [SMD = − 0.50, 95% CI (− 1.49, 0.49), P = 0.32], nor did it reduce HbA1c [SMD = − 1.22, 95% CI (− 2.90, 0.47), P = 0.16] after a duration > 3 months in all studies. However, other styles of Tai Chi significantly reduced FBG [SMD = − 0.90, 95% CI (− 1.28, − 0.52), P 3 months, while no significant reduction in FBG [SMD = − 0.34, 95% CI (− 0.76, 0.08), P = 0.12] or HbA1c [SMD = − 0.34, 95% CI (− 0.76, 0.08), P = 0.12] was found after a duration ≤3 months. Conclusions Tai Chi seems to be effective in treating type 2 diabetes. Different training durations and styles result in variable effectiveness. The evidence was insufficient to support whether long-term Tai Chi training was more effective.

Traditional Chinese medicine (TCM) is effective in preventing and treating all manner of diseases, which has been incorporated into the latest global medical outline (Ver.2019) by World Health Organization (WHO). As one of the most important characteristics of TCM, syndrome differentiation (SD) provides curative effect assurance. SD is a high-dimensional complex function with symptoms/signs as input and syndrome type as output. Artificial neural network (ANN) provides an all-purpose data-driven solution to fit high-dimensional complex function, making ANN a promising approach for modeling intelligent SD (ISD) for TCM. In this paper, we chose chronic obstructive pulmonary disease (COPD) as an example for investigating ISD for TCM based on ANN. First, we built a full-group ANN model that combines ANN with full-group datasets composed of 18471 real clinical records. In addition, we built four extra models with ANN and four subgroup datasets. For comparison, we built another four models with four traditional machine-learning algorithms and the full-group datasets. We used accuracy and F1-scores to evaluate the models' performance. With an accuracy of 86.45% and an F1 score of 82.93%, the full-group ANN model outperformed the four comparison models built from traditional machine-learning algorithms, and however, the four subgroup models achieved a better performance than the full-group ANN model. We concluded that the ANN can potentially provide a way for ISD for TCM, and our subgroup modeling suggests ideas for further optimizing the ISD.

Recurrent spontaneous abortion is associated with abnormal maternal tolerance to the semi-allogenic fetus, wherein the Th17/Treg axis plays a crucial role. Adiponectin (APN) is an adipocytokine that is shown to be a novel negative T-cell regulator and induce immune tolerance. The CBA/J × DBA/2 mating was used as an abortion-prone model to investigate whether the addition of recombinant adiponectin (rAPN) improves the pregnancy outcome. Recombinant adiponectin therapy reduced the abortion rate in abortion-prone model. It skewed the ability of serum cytokine production toward a Treg bias and induced APN production. Flow cytometry revealed that rAPN administration expanded the splenic CD4+CD25+ regulatory T-cell (Treg) population and reduced the Th17 cell populations in CBA/J × DBA/2 matings. RT-PCR revealed that rAPN administration induced the expression of AdipoR1 and AdipoR2 mRNA at the maternofetal interface. Recombinant adiponectin administration induced FoxP3 and reduced RORγt expressions at the maternofetal interface. In vitro experiment also showed that rAPN treatment enhanced the FoxP3 mRNA and protein expression and decreased the RORγt expression in splenic lymphocytes of abortion-prone mice. Blocking the different signal transduction pathways downstream of APN, p38MAPK inhibitor (SB203580) and STAT5 inhibitor (Pimozide) could abrogate the regulatory effect of rAPN on FoxP3 and RORγt expression, while STAT3 inhibitor (Stattic) and AMPK inhibitor (p5499) did not exert any influence. Thus, the current results demonstrated that rAPN therapy improves pregnancy outcome in a murine model of abortion by expanding the Treg cell population and function and decreasing the Th17 cell population and function via a p38MAPK-STAT5 pathway.Summary SentenceAdiponectin, which is essential for lipid metabolism and homeostasis, is beneficial for pregnancy outcome through improving Th17 and Treg populations; the process is associated with the activation of p38MAPK-STAT5 pathway.

Background Thyroid nodules (TN) are discrete lesions within the thyroid gland and are a common clinical problem detected in 19% to 68% of people. TN are more common as age increases and occur more frequently in women. TN can cause pressure symptoms, cosmetic complaints, and thyroid dysfunction. Treatment for benign thyroid nodules includes thyroid hormone therapy, surgery, radioiodine treatment, percutaneous ethanol injection therapy, and laser or radiofrequency treatment to shrink nodules. In China and many other countries, doctors use Chinese herbal medicines (CHM) to treat TN. However, systematic review and meta-analysis has not been found to assess the effects and safety of CHM in curing TN at present. Hence, the systematic review is conducted to scientifically and methodically evaluate the value of its effectiveness and safety of CHM on TN. Methods Literatures related to CHM for TN from the establishment of the database to November 2020 will be retrieved from the following databases: PubMed, Excerpta Medica Database (EMBASE), MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform (ICTRP), Wanfang Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP). There are no language restrictions for retrieving literatures. Case reports, animal studies, editorials, expert opinions, reviews without original data, and studies on pediatric population were excluded. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in TN patients will be put in the study including nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data. Result This study will provide high-quality available evidence for the treatment of TN with CHM based on nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. Conclusion The systematic review will to evaluate the efficacy of CHM in treating benign thyroid nodules in adults and provide evidence for clinicians. Inplasy registration number INPLASY2020120093.

Background: Diabetic peripheral neuropathy (DPN) is 1 of the most common clinical complications of diabetes, which seriously affects the quality of life of patients and causes a substantial economic burden on diabetes care. The pathogenesis of DPN is complex. There is no targeted treatment method, and mainstream treatment methods have low efficacy and large side effects. Traditional Chinese medicine has rich clinical experience in the prevention and treatment of diabetic peripheral neuropathy, which has dramatically improved the quality of life of patients. It is clinically proven that traditional Chinese medicine fumigants (TCMF) have apparent effects in treating diabetic peripheral neuropathy. Therefore, we aim to systematically review the effectiveness and safety of TCMF for DPN. Methods: We will search the following databases: PubMed, Embase, Cochrane Library, MEDLINE, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Cqvip Database, and Wanfang Data. Besides, we will also search for clinical trial registrations, potential grey literature, relevant conference abstracts, and reference lists of established studies. The studies published from the inception of the database to November 2020 will be retrieved. The randomized controlled trials on TCMF for DPN will be included. Also, we will search for clinical trial registrations, potential grey literature, relevant conference abstracts, and reference lists of established studies. The main result is clinical efficacy and nerve conduction velocity. Fasting blood glucose, 2 hours postprandial blood glucose, blood lipid, glycosylated hemoglobin, and adverse events are secondary results. We will perform the analyses using RevMan V.5.3 software. Results: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of TCMF in the treatment of DPN. Conclusions: This systematic review will evaluate the effectiveness and safety of TCMF in the treatment of DPN, and provide the latest evidence for clinical application. INPLASY registration number: INPLASY2020110137.

Background Conflicting results have been reported regarding the effect of metformin on adiponectin levels in women with polycystic ovary syndrome (PCOS). This meta-analysis reviewed all studies comparing adiponectin levels before and after metformin treatment in PCOS women. Additionally, changes in other indicators, including long-term complications associated with PCOS, such as inflammatory, metabolism factors and hormonal profile, were investigated following metformin treatment. We conducted subgroup analysis based on body mass index (BMI) stratification and appropriate pooling. Methods We searched literature in PUBMED, EMBASE, the Cochrane Library, and CNKI databases. The main meta-analysis included 11 studies containing data on 353 subjects. Results Metformin treatment was associated with significantly increased serum adiponectin concentrations [10 studies, random-effects SMD (95% CI) −0.58 [-1.03, −0.13]; I2 = 86%; P = 0.01]. Additionally, the meta-analysis revealed that circulating tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74–1.28, P＜0.00001) and 0.48(95% CI: 0.35–0.60, P＜0.00001). Conclusion Following metformin administration, serum adiponectin concentrations of PCOS women were found to be significantly increased, accompanied by a significant improvement in other indicators. Further investigation with a larger sample size should be conducted to validate optimal dose and duration of metformin.

Background: Aging is a phenomenon that human's physiology and psychology is progressive decline for natural environment. Health Qigong, as a convenient and effective exercise therapy,is widely used for anti-aging. However, there are no systematic reviews or meta-analysises to evaluate the efficacy and safety of Health Qigong on anti-aging. Methods: We will systematically search for 7 English databases(PubMed, Excerpta Medica Database, MEDLINE, Web of Science, Cochrane Library, SpringerLink, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases(namely the China National Knowledge Infrastructure Database, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical Literature Database) from their inceptions to August 2020. Randomized controlled trials (RCTs) using Health Qigong to anti-aging will be included. After the selection and extraction of eligible studies, a meta-analysis will be undertaken to assess the efficacy and safety of Health Qigong on anti-aging. Moreover, study selection, data extraction, and the evaluation of the methodological quality of trials will each be independently completed by at least 2 researchers. The Review Manager Software V.5.3 will be employed for meta-analysis to assess the risk of bias, data synthesis, and subgroup analysis. Results: This review will provide the latest knowledge and evidence on the efficacy and safety of Health Qigong for anti-aging through the analysis of various evaluation scales. Conclusion: The conclusion of this review will help clinicians provide effective exercise therapy for anti-aging. Registration number: INPLASY202090017

Background Yangyin Fuzheng Jiedu Prescription (YFJP) is a traditional Chinese medicine (TCM) indicated for the treatment of hepatocellular carcinoma (HCC). Its potential targets and molecular mechanisms are not clear. Therefore, this study intends to explore the molecular mechanism of YFJP based on network pharmacology analysis and in vitro validation. Methods and results Through univariate and multivariate analyses and survival analysis in HCC patients with or without YFJP treatment we found that drinking alcohol, alfafeto protein ≥ 400 ng/l, baseline portal vein tumor thrombus and total bilirubin level ≥ 18.8 μM) were independent risk factors for poor prognosis, while red blood cell count ≥ 4 × 109/l and TCM treatment were independent protective factors. Besides, YFJP prolonged the cumulative survival of HCC patients. Using online pharmacological methods, we obtained 58 relevant compounds and molecular 53 targets. By using scratch test, Transwell assay, EdU assay, and TUNEL staining, we found that YFJP-containing serum repressed the migration, invasion and proliferation of HCC cells in vitro, and induced cell apoptosis. Moreover, YFJP diminished the gene expression of TP53, CCND1, p-EGFR, EGF, VEGFA, JUN, IL6, COX-2, AKT1, and MAPK1 in HCC cells, but elevated the expression of ESR1 and CASP3. Conclusions Taken together, results showed that YFJP attenuated HCC progression through mediating effects on HCC-related genes.

Summary Obesity is an important risk factor and a potential treatment target for hepatic steatosis. The maladaptation of hepatic mitochondrial flexibility plays a key role in the hepatic steatosis. Herein, we found that hepatocyte-like cells derived from human adipose stem cell of obese patients exhibited the characteristics of hepatic steatosis and accompanied with lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. The GSK3 inhibitor CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, the basal oxygen consumption rate, and the fatty acid oxidation of the hepatocytes of obese patients by upregulating the expression of the transcription factor PGC-1α, TFAM, and NRF1 involved in mitochondrial biogenesis. Moreover, CHIR-99021 decreased the lipid droplets size and the triglyceride levels in hepatocytes of obese patients. The results demonstrate that GSK3 inhibition ameliorates hepatic steatosis by elevating the mitochondrial function in hepatocytes of obese patients., Graphical abstract, Highlights • Obese patients’ adipose-stem-cell-derived hepatocytes reveal hepatic steatosis • Hepatic steatosis is accompanied the mitochondrial dysfunction • The mitochondrial dysfunction is governed by the low expression PGC-1α, TFAM, and NRF1 • GSK3 inhibitor ameliorates hepatic steatosis via mitochondrial dysfunction modulation, human metabolism; molecular biology

BackgroundThis paper developed and described a risk-based quality control approach of clinical trials for clinical trial sites to improve the quality control process and ensure the quality of data.Methods Based on the trial experience, well versed experts and the findings of previous literature, an integrated risk-based quality control approach is developed centered on three cornerstones: risk assessment, central data review, and triggered, adaptive on-the-spot or remote inspection.Results We have developed an innovative risk-based quality control approach for clinical trials including risk assessment, development of quality control plan, implementation of quality control activities, development and review of quality control report, undertake actions arising from quality control report, and the update of risk assessment results or quality control plan, which fuses the idea of PDCA circle and quality by design.Conclusion Our RBQC methodology can significantly improve the clinical quality control process and the monitoring-audit triggered procedure can synchronize the activities of site, sponsor and CROs to achieve all-win. It is an innovative and effective approach.

The electric shock has been proposed as one of the new needling sensations in recent years. In acupuncture sensation scales, the electric shock is included by ASS and SNQS, but not SASS, MASS, and C-MMASS. Some scholars argue that the electric shock is a normal needling sensation, but some researchers do not agree with this view. This problem has not been resolved due to a lack of evidence from basic research. Literature and research point out that the electric shock is caused by inserting a needle into the nerve directly. A question of considerable scientific and practical interest is whether the electric shock should be a normal needling sensation. In this article, we review the historical documentation of the needling sensation and the process of formulating and improving acupuncture sensation scales to suggest that the electric shock may not be a normal needling sensation. Secondly, we collected and analyzed cases of nerve injury caused by acupuncture accompanied by the electric shock and why acupuncture caused the electric shock without nerve injury. It suggests that there may be a correlation between the electric shock and peripheral nerve injury, and acupuncture manipulation is an essential factor in adverse acupuncture events. Finally, we put forward that the electric shock during acupuncture is a warning sign that the peripheral nerve may be injured, rather than a normal needling sensation. In the future, we hope to have experimental studies on the mechanism of the electric shock or observational studies on the correlation between the electric shock and peripheral nerve injury to verify.

Background Yangyin Fuzheng Jiedu Prescription (YFJP), a formulated Chinese herbal medicine, has been used for several decades in the treatment of hepatocellular carcinoma (HCC). Previous studies have demonstrated its anti-tumor efficacy, but the mechanism of action remains uncharacterized. This study aims to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice. Purpose This study aimed to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice. Methods A total of 50 male H22 tumor-bearing mice were randomly divided into 6 groups and continuous administered either different doses of YFJP or cyclophosphamide (CTX) or normal saline. for 2 weeks. The tumor appearance was observed by taking photos, and the tumor volume, weight, spleen and thymus index were calculated. Morphology of tumor infiltrating lymphocytes and the CD8+ T lymphocytes were detected through HE staining immunohistochemistry respectively. The frequency of CD3+, CD8+ T cell subsets and co-inhibitory receptors PD-1, TIGIT, Tim-3 on CD8+ T cell in spleen, peripheral blood and tumor tissue was performed by flow cytometry. Meanwhile, the killing and apoptotic functions of CD8+ T cells in tumor tissues were also detected by the same method. The levels of cytokines in peripheral blood were detected by Milliplex map mouse highs sensitivity T Cell kit. The expression of T cell transcription factor T-bet and Eomes in tumor tissues were observed by Western blot. Results We found that YFJP could effectively inhibit the solid tumor growth and spleen indexes, but showed little effect on the body weight in the established mouse model of HCC. Furthermore, we investigated the effect of YFJP on the phenotypic and functional changes of T cells. The results showed that YFJP could maintain the high ratio of CD3+ and CD8+ T cells in the peripheral blood, spleen, and tumor tissues while decreasing the expression of programmed cell death-1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin domain and mucin domain-3 (Tim-3) in CD8+ T cells, respectively. Surprisingly, PD-1/Tim-3 double-positive T cells in the peripheral blood and tumor tissues were significantly decreased. Additionally, YFJP restored the cytotoxicity of tumor-infiltrating T cells and delayed their apoptosis in H22 tumor-bearing mice. In addition, treatment with YFJP significantly decreased the expression of inflammatory and immunosuppressive cytokines (including IL-1β, IL-6, and IL-10) in the serum and tumor tissues whereas enhancing that of effector cytokines TNF-α, and IFN-γ. Moreover, T cell transcription factors T-bet increased and Eomes degraded in the tumor tissues upon YFJP treatment. Conclusion In conclusion, these results demonstrated that YFJP could simultaneously exert anti-tumor immune response in H22 tumor-bearing mice by alleviating T cell exhaustion and immunosuppression.

Asthma can be complex and difficult to manage. Patients often seek alternative treatment options, including Traditional Chinese Medicine (TCM). The paradigms that inform TCM treatments include a philosophy focusing on modifying the whole body status ('bian zheng') to treat the lungs. TCM practitioners use personalized treatment plans based on clusters of clinical patterns (eg. cold-related wheezing, kidney insufficiency/energy-deficiency-related wheezing). TCM includes herbal remedies and non-oral therapies such as cupping, acupuncture, and massage. The efficacy of TCM treatments of asthma is not well described as the majority of studies are published only in Chinese literature. We reviewed all available clinical trials in CNKI, Chaoxin, Wanfang, CQVIP, Springer-link, Science Direct, and Pubmed. Papers in Chinese were translated by dual lingual TCM and Western medicine doctors. Based on the identified studies, TCM is a safe additive treatment to Western medicine that can improve both symptoms and quality of life for patients with asthma.

Summary Surface fogging reduces light transmission of optically clear materials and causes various problems in daily life. Transparent photothermal materials have recently emerged as an eco-friendly and sustainable solution to surface fogging. However, most reported photothermal materials only exploited the broadband spectrum of solar energy, and the spectral feature has yet to be tuned to optimize the visibility and photothermal effect simultaneously. Here, we develop a highly transparent, photothermally selective coating, based on solution-processed cesium-doped tungsten trioxide nanoparticles. The transparent selective photothermal coating provides a visible transmittance up to 82% and a high absorption of ultraviolet and near-infrared light >90%, and achieves a temperature increase by 38°C under 1-sun illumination, resulting in remarkable antifogging and defogging abilities under extremely frigid or humid conditions. Large-scale complex surfaces with photothermal coatings are deployed in field antifogging tests as well as long-term durability tests, showing their great potential in antifogging applications.

BACKGROUND Thyroid autoimmune disease (TAI) has been verified to be related to multiple adverse pregnancy outcomes. A growing number of evidences highlight the protective roles of glucocorticoid on the treatments of TAI. This meta-analysis aimed to study whether it is beneficial to add glucocorticoid treatment in infertile women with TAI when they are undergoing assisted reproductive technology (ART). METHODS We conducted a systematic search in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu China Science and Technology Journal Databases (VIP database) up to September 10, 2020. The Revman 5.3 software was utilized for data statistics. We used a random-effects model to analyze data and the odds ratio (OR) combining with 95% confidence interval (95% CI) were employed to reveal the results. RESULTS Three publications with 237 antithyroid antibody (ATA)-positive and 384 ATA-negative women were included in the final analysis. Overall, glucocorticoid therapy showed satisfying effects on improving clinical pregnancy rate (OR = 4.63, 95% CI [2.23, 9.58], I2 = 0.0%, P

The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell‐derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell‐derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell‐derived hepatocyte‐like cells (hASC‐HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC‐HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC‐HLCs also attenuated the up‐regulation of the metabolic function of hASC‐HLCs in a nuclear receptor‐dependent manner. These data elucidate integrin‐Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non‐parenchymal cell‐derived matrix.

Over the past two decades, the viewpoint of atherosclerosis has been replaced gradually by a lipid-driven, chronic, low-grade inflammatory disease of the arterial wall. Current treatment of atherosclerosis is focused on limiting its risk factors, such as hyperlipidemia or hypertension. However, treatment targeting the inflammatory nature of atherosclerosis is still very limited and deserves further attention to fight atherosclerosis successfully. Here, we review the current development of inflammation and atherosclerosis to discuss novel insights and potential targets in atherosclerosis, and to address drug discovery based on anti-inflammatory strategy in atherosclerotic disease.

Objective: To elucidate the protective effect of Gan Shen Fu Fang (GSFF) on liver endothelial cells in common bile duct-ligated (CBDL) rats. Materials and Methods: Cirrhosis was induced by common bile duct ligation. The rats were divided into three groups: sham group, CBDL group, and GSFF group. After 2 weeks of ligation, rats in the GSFF group were administered GSFF. After 4 weeks, the hydroxyproline (Hyp) content of liver tissues was spectrophotometrically determined. The histological changes were evaluated by H and E and Masson staining. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to observe the ultrastructural changes in the liver, especially in the liver sinusoidal endothelial cells (LSECs). Results: Hyp synthesis was significantly inhibited by GSFF, which agreed with the results from H and E and Masson staining for liver fibrosis. The TEM observations of CBDL rats revealed reduced hepatocyte microvilli and deposited fibrous tissue underneath LSECs. SEM confirmed the TEM findings and showed that the fenestrae of LSECs decreased and even disappeared in CBDL rats. The morphological results indicated hepatic sinusoid capillarization. GSFF promoted the restoration of fenestrae and reversed hepatic sinusoid capillarization. Conclusion: GSFF can inhibit Hyp synthesis, restore the fenestrae of LSECs, and reverse hepatic sinusoid capillarization in CBDL rats. These results provide a basis for future detailed investigations of the mechanism of action of GSFF in LSECs.