Identification of novel homozygous asthenoteratospermia-causing ARMC2 mutations associated with multiple morphological abnormalities of the sperm flagella.

PURPOSE: To identify the genetic causes of multiple morphological abnormalities in sperm flagella (MMAF) and male infertility in patients from two unrelated Han Chinese families. METHODS: Whole-exome sequencing was conducted using blood samples from the two individuals with MMAF and male infertility. Hematoxylin and eosin staining and scanning electron microscopy were performed to evaluate sperm morphology. Ultrastructural and immunostaining analyses of the spermatozoa were performed. The HEK293T cells were used to confirm the pathogenicity of the variants. RESULTS: We identified two novel homozygous missense ARMC2 variants: c.314C > T: p.P105L and c.2227A > G: p.N743D. Both variants are absent or rare in the human population genome data and are predicted to be deleterious. In vitro experiments indicated that both ARMC2 variants caused a slightly increased protein expression. ARMC2-mutant spermatozoa showed multiple morphological abnormalities (bent, short, coiled, absent, and irregular) in the flagella. In addition, the spermatozoa of the patients revealed a frequent absence of the central pair complex and disrupted axonemal ultrastructure. CONCLUSION: We identified two novel ARMC2 variants that caused male infertility and MMAF in Han Chinese patients. These findings expand the mutational spectrum of ARMC2 and provide insights into the complex causes and pathogenesis of MMAF.

Characterization of platelet-related genes and constructing signature combined with immune-related genes for predicting outcomes and immunotherapy response in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is a highly malignant subtype of non-small cell lung cancer with poor prognosis. Platelets are known to play a critical role in cancer development and progression, and recent studies suggest that they can also regulate immune response in tumors. However, the relationship between platelet-related genes (PRGs) and LUSC prognosis and tumor microenvironments remains unclear. In this study, we used multiple bioinformatics algorithms to identify 25 dysregulated PRGs that were significantly associated with LUSC prognosis. We found that PRGs were involved in multiple biological processes, particularly in the tumor microenvironment, and that platelet-related scores (PRS) were a risk factor. Additionally, we established a 6-gene prognostic signature combining PRGs and immune-related genes that accurately predicted outcomes and immunotherapy efficacy in LUSC patients. Our study provides a comprehensive analysis of the biological functions and potential therapeutic targets of PRGs in LUSC, which may inform the development of new treatments for this disease.

Using AGREE II reporting checklist to evaluate the quality of Tuina clinical practice guidelines.

Objective: The objective of this study is to evaluate the methodological quality of Tuina clinical practice guidelines (CPGs). Methods: Computer searches of China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library, Embase, and other databases were conducted to search for published guidelines on Tuina, with a search time frame from database creation to March 2021. Four evaluators independently used the Appraisal of Guidelines for Research and Evaluation II instrument to evaluate the quality of the included guidelines. Results: A total of eight guidelines related to Tuina were included in this study. The quality of reporting was low in all included guidelines. The highest quality report had a total score of 404 and was rated as "highly recommended." The worst guideline had a final score of 241 and was rated as "not recommended." Overall, 25% of the included guidelines were recommended for clinical use, 37.5% were recommended after revision, and 37.5% were not recommended. Conclusion: The number of existing Tuina clinical practice guidelines is limited. The methodological quality is low, far from the internationally accepted clinical practice guideline development and reporting norms. In the future, reporting specifications of guidelines and the methodology of guideline development, including the rigor of the guideline development process, the clarity, application, and independence of reporting, should be emphasized in the development of the Tuina guidelines. These initiatives could improve the quality and applicability of clinical practice guidelines to guide and standardize the clinical practice of Tuina.

A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility.

Male infertility is a major reproductive disorder, which is clinically characterized by highly heterogeneous phenotypes of abnormal sperm count or quality. To date, five male patients with biallelic loss-of-function (LOF) variants of PARN-like ribonuclease domain-containing exonuclease 1 ( PNLDC1 ) have been reported to experience infertility with nonobstructive azoospermia. The aim of this study was to identify the genetic cause of male infertility with oligo-astheno-teratozoospermia (OAT) in a patient from a Chinese Han family. Whole-exome and Sanger sequencing analyses identified a homozygous LOF variant (NM_173516.2, c.142C>T, p.Gln48Ter) in PNLDC1 . Hematoxylin and eosin staining revealed that the spermatozoa of the patient with OAT had an irregular head phenotype, including microcephaly, head tapering, and globozoospermia. Consistently, peanut agglutinin staining of the spermatozoa revealed a complete or partial loss of the acrosome. Furthermore, the disomy rate of chromosomes in the patient's spermatozoa was significantly increased compared with that of a fertile control sample. We reported an LOF variant of the PNLDC1 gene responsible for OAT.

Research progress in the correlation between reproductive tract microbiota and intrauterine adhesion. / ç”Ÿæ®–é“å¾®ç”Ÿç‰©ç¾¤ä¸Žå®«è ”ç²˜è¿žçš„ç›¸å ³æ€§ç ”ç©¶è¿›å±•.

Intrauterine adhesion (IUA) is caused by damage of the basal layer of endometrium, which leads to fibrosis of the endometrium and the formation of adhesion, resulting in partial or complete occlusion of the uterine cavity, abnormal menstruation, infertility or recurrent miscarriage. The prevalence of IUA in women has been increasing in recent years, and the high recurrence rate of moderate to severe IUA makes IUA treatment more challenging. Iatrogenic endometrial injury is the main cause of IUA. However, the incidence of IUA and the severity of IUA vary among patients who have received similar uterine operations, suggesting that there may be other synergistic factors in the development of IUA. There is a certain correlation between the pathogenesis and the microbiota of the gential tract. In many IUA patients, it has been observed that the probiotics such as Lactobacillus in the vagina is significant reduced, and the pathogenic bacteria such as Gardnerella and Prevotella are excessive growth. The reproductive tract microbiota can be involved in the development and progression of IUA via impacting immune function and metabolism.

Tuina combined with Adjuvant therapy for lumbar disc herniation: A network meta-analysis.

OBJECTIVE: To directly or indirectly compare the effectiveness and pain relief of TN combined with different treatments for lumbar disc herniation (LDH). METHODS: The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Biomedical Literature database (CBM), Chinese Scientific Journal Database (VIP), PubMed, Embase, Cochrane library, and Web of Science were searched from inception to July 2020. Only full texts of randomized controlled trials (RCTs) that make comparisons between Tuina and Tuina combined with other methods were included. We extracted trial data and assessed the risk of bias by two reviewers independently. We pooled continuous data in standard mean differences (SMDs) and binary data in risk ratios (RRs), and provided 95% confidence intervals. The primary outcomes were the effectiveness rate. The secondary outcome was pain measurements including visual analog scale (VAS) scores. RESULTS: Forty-four trials which included 4741 participants and 16 kinds of interventions were selected in our study. Tuina combined with Acupuncture was the most frequently investigated intervention. Five (31%) kindnesces (SMDs) and binary data in risk ratios (RRs), and provided 95% confidence intervals. The primary outcomes were the effectiveness rate. The secondary outcome was pain measurements including visual analog scale (VAS) scores. RESULTS: Forty-four trials of treatments among 15 increased the healing rate more significantly compared with Tuina(TN), including Tuian combined with Traction and formula(TN + TRA + FM), Tuina combined with formula(TN + FM), Tuina combined with Traction and Acupuncture(ACU + TN + TRA), Tuian combined with Traction(TN + TRA), Tuina combined with Electroacupuncture(EA + TN), Tuina combined with the warm needle(TN + WN), Tuina combined with Acupuncture(ACU + TN). Seven treatments including Tuina combined with Electroacupuncture(EA + TN), Tuian combined with Traction and formula(TN + TRA + FM), Tuina combined with Acupuncture(ACU + TN), Tuina combined with formula(TN + FM), Acupuncture(ACU), Tuian combined with Traction(TN + TRA), Tuina combined with the warm needle(TN + WN) had better effects in reducing pain intensity compared with Tuina, range from 0.01 (95%Crl 0-0.08) for EA + TN to 0.30 (95%Crl 0.20-0.45) for TN + WN. CONCLUSIONS: According to the comprehensive review, Tuina combined with Traction and formula(TN + TRA + FM) seemed to be the most recommendable treatment which is more affordable and effective. However, all the available evidence was of low quality, so more high-quality studies are expected to confirm the effectiveness. REGISTRATION NUMBER: PROSPERO CRD42020193068.

"One Stone, Four Birds" Ion Engineering to Fabricate Versatile Core-Shell Organosilica Nanoparticles for Intelligent Nanotheranostics.

Developing effective intelligent nanotheranostics is highly desirable for cancer treatment but remains challenging. In this study, an acidic tumor microenvironment-activated organosilica nanosystem, namely AD-Cu-DOX-HA, is straightforwardly constructed, which is composed of aggregation-induced emission (AIE)-active photosensitizer, copper ion-engineered aminosilica, direct coordination polymer of doxorubicin (DOX), and targeting component hyaluronic acid (HA). AD-Cu-DOX-HA is able to accurately distinguish cancer cells over normal cells; meanwhile, it simultaneously exhibits selective accumulation and copper ion-mediated rapid disassembly and turn-on fluorescence in tumor tissue, consequently achieving efficient tumor diagnosis and tumor-growth inhibition through fluorescence imaging-navigated synergetic photodynamic therapy, copper ion-mediated chemodynamic therapy, and DOX-enabled chemotherapy. This work thus brings fresh insight into the exploration of versatile theranostics and presents a momentous advance for potential clinical cancer treatment.

Effects of Dopamine-Modified and Organic Intercalation on the Thermophysical Properties of Octadecane/Expanded Vermiculite Composite Phase Change Materials.

For phase change materials (PCMs) confined in porous structure, the interface interaction between the PCM and the porous skeleton is the key factor to determine the thermal storage performance of PCM. In this study, the modified expanded vermiculite (EVM) was prepared by dopamine modification and DTA+ intercalation method and a series of EVM-based composite phase change materials with form shape (fs-CPCMs) were prepared by physical impregnation using n-octadecane as PCMs. The heat storage performance of the composite phase change materials were improved obviously, and the encapsulation ratio is increased to 84.7% and 83.1%. The nonisothermal crystallization process of prepared composite phase change material were further studied. The effects of dopamine modification and organic intercalation on the encapsulation performance of EVM-based fs-CPCMs were analyzed. The results of XRD, FT-IR, thermal cycle, and TGA tests showed that EVM-based composite phase change materials had good chemical compatibility, thermal reliability, and thermal stability. This study provides a theoretical basis for the preparation of EVM-based fs-CPCMs with high thermal stability and good heat storage performance.

International Publication Trends in Low Back Pain Research: A Bibliometric and Visualization Analysis.

Background: Although there is a growing research base on low back pain, the bibliometric literature related to it is deficient. The aim of this study was to conduct a bibliometric and visualization analysis of low back pain and to provide a broad view of the current trends in LBP research and a potential guide in this discipline. Methods: The authors searched the Web of Science to extract publications regarding low back pain, and found a total of 12,249 publications during a period of 22 years, among which 12,242 were eligible. We classified and analyzed publications such as total citations, average citations per item, H-index, research types, countries/regions, institutions, and journals using standard bibliometric indicators. Bibliometric approaches (VOSviewer1.6.13 and CiteSpace 5.8.3) were also available for gathering information and explore the trends of research. Results: Conspicuously, over the past 22 years, an increasing number of scholars have specialized in the research of LBP, exerting the boom in articles. The largest number of document type was that of articles. Under modern conditions, regional distinction existed in the research of low back pain and developed countries preceded others. Research individuals and institutions were preoccupied by respective aspects. Visualization analysis provided objective information for potential collaborators and cooperative institutions. Furthermore, most burst keywords varied during different periods. Conclusions: The map of research on LBP obtained by our analysis is expected to help researchers to efficiently and effectively explore LBP.

Exogenous proanthocyanidins improve tolerance of Cu-toxicity by amelioration of oxidative damage and re-programming of gene expression in Medicago sativa.

Excess copper (Cu) in soil due to industrial and agricultural practices can result in reduced plant growth. Excess Cu resulted in severely retarded root growth with severe discoloration of Alfalfa (Medicago sativa) and Medicago truncatula. Growth in the presence of hydrogen peroxide resulted in similar symptoms that could be partially recovered by the addition of the reductant ascorbic acid revealing damage was likely due to oxidative stress. The addition of proanthocyanidins (PAs) in the presence of Cu prevented much of the damage, including plant growth and restoration of lignin synthesis which was inhibited in the presence of excess Cu. Transcriptome analyses of the impact of excess Cu and the amelioration after PAs treatment revealed that changes were enriched in functions associated with the cell wall and extracellular processes, indicating that inhibition of cell wall synthesis was likely the reason for retarded growth. Excess Cu appeared to induce a strong defense response, along with alterations in the expression of a number of genes encoding transcription factors, notably related to ethylene signaling. The addition of PAs greatly reduced this response, and also induced novel genes that likely help ameliorate the effects of excess Cu. These included induction of genes involved in the last step of ascorbic acid biosynthesis and of enzymes involved in cell wall synthesis. Combined, these results show that excess Cu causes severe oxidative stress damage and inhibition of cell wall synthesis, which can be relieved by the addition of PAs.

Acupuncture for diabetic peripheral neuropathy: An overview of systematic reviews.

BACKGROUND: Acupuncture has been widely used to treat diabetic peripheral neuropathy (DPN) in China as a complementary and alternative therapy. This study aims to summarize the characteristics and evaluate the methodology quality of the systematic reviews (SRs) regarding acupuncture for DPN. METHODS: A comprehensive literature search was performed from inception to February 2020. We assessed the methodological quality of the included SRs with the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool, adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to evaluate the reporting characteristics of included SRs, and utilized the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of evidence for outcomes including total effective rate, sensory nerve conduction velocity, motor nerve conduction velocity and adverse events. One-way analysis of variance and multiple linear regression were conducted to evaluate the associations between characteristics and two index scores (PRISMA and AMSTAR 2). RESULTS: Eighteen SRs were included in this overview. The methodology quality of the included SRs ranged from very low to high. Only protocol registration and funding source reported were associated with the AMSTAR 2 index scores, while no variable showed significant difference in the PRISMA scores. The overall quality of evidence in included SRs ranged from "very low" to "moderate". CONCLUSION: This overview suggested beneficial effects of acupuncture on DPN, whereas the results should be interpreted with cautious owing to methodology flaws, providing reference for further improvement of the study design.

The effectiveness and safety of Tuina for tension-type headache: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Tension-type headache (TTH) is one of the most common primary headache diseases in the world and has a serious negative impact on the physical and mental health of patients. Tuina is now widely used to treat tension-type headaches. This article aims to systematically review the evidence about the effectiveness of Tuina on the effectiveness rate, pain intensity, and impact of headache in individuals with TTH. METHODS: Eight databases for randomized controlled trials (RCTs) of Tuina were included in treatments for TTH. Cochrane Collaboration's tool was applied to evaluate the quality of the studies. Confidence in the effect estimates was determined with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We use the software STATA 12.0 for meta-analysis and TSA software for test sequence analysis. RESULTS: Seven studies were included with a total sample of 1228 individuals. Meta-analysis results showed that Tuina was superior to drugs for improving the effectiveness rate (RR = 1.49, 95%CI: 1.25 to 1.77, p < 0.01, low evidence). A visual analog scale (VAS) score of Tuina was significantly lower than that of drugs (WMD = -0.738, 95% CI: -1.128 to -0.349, p < 0.01, moderate evidence). The trial sequential analysis showed that the effectiveness of Tuina for TTH was accurate. Adverse events were tolerable. CONCLUSION: Tuina has a certain effect in treating tension headache. However, due to the low level of methodological quality included in the article, this conclusion should be considered cautiously. More studies are necessary to strengthen the evidence regarding the effectiveness and safety of Tuina for subjects with TTH.

Evaluating the Characteristics, Reporting and Methodological Quality of Systematic Reviews of Acupuncture for Low Back Pain by Using the Veritas Plot.

OBJECTIVE: To evaluate systematic reviews (SRs) of acupuncture for low back pain (LBP) in terms of characteristics, reporting and methodological quality using a Veritas plot and to explore factors that may be associated with methodological quality and reporting quality. STUDY DESIGN AND SETTING: We searched 8 electronic bibliographic databases to find all SRs, and we evaluated the SRs' quality in 6 dimensions, including publication year, design type, homogeneity, risk of publication bias, methodological quality by Assessment of Multiple Systematic Reviews (AMSTAR) 2 and reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Excel 2010 and Adobe Illustrator CC were used to draw and optimize Veritas plots. Exploratory analysis was done using SPSS software version 23.0 to explore factors related to AMSTAR-2 and PRISMA scores. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence quality evaluation tool was used to grade all the outcome indicators in the included literature. RESULTS: We included 19 SRs in the analysis. Literature quality rank scores ranged from 9.67 to 17.00, with an average score of 13.18 ± 2.35. The average score of AMSTAR-2 was 7.47, and the average score of PRISMA was 18.47. Overall, the main issues were research strategies, inclusion and exclusion criteria, publication bias, and registration in PROSPERO. The results of exploratory analysis showed that duplication of literature selected and appropriate tools to assess the risk of bias were related to the AMSTAR-2 score, and the summary of evidence was related to the PRISMA score. The GRADE quality evaluation results showed mainly low quality. CONCLUSION: The quality of SRs on acupuncture for low back pain should be improved, mainly by strengthening the methodological quality and reporting quality. The Veritas plot is an effective graphical evaluation method that is worth popularizing.

Tuina for cervical vertigo: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Cervical vertigo (CV), one of the most common causes of vertigo, makes patients feel dizzy, which seriously affects patients' lives. As a traditional Chinese bone-setting manipulation, Tuina is widely used to treat CV. This article aims to evaluate the effectiveness and safety of Tuina for CV. METHODS: Nine databases were searched. Methodological quality was evaluated with the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to determine confidence in the effect estimates. Stata 12.0 software was used to carry out the meta-analysis, and a trial sequential analysis (TSA) was performed with TSA 0.9. RESULTS: Nine randomized controlled trials (RCTs) were included. Low-quality evidence suggested that Tuina showed a significantly higher effectiveness rate compared to massage therapy (risk ratio (RR) = 1.11, 95% confidence intervals (CI): 1.05 to 1.17, p < 0.0001) and cervical traction (RR = 1.37, 95% CI: 1.09 to 1.72, p = 0.007; I2 = 0%, p = 0.826). Two trials reported that Tuina was better than acupuncture (RR = 1.40, 95% CI: 1.07 to 1.83) or betahistine mesilate (RR = 1.17, 95% CI: 0.99 to 1.37) based on an improved effectiveness rate. Low-quality evidence showed that Tuina was superior to massage therapy in improving scores on the evaluation scale for cervical vertigo (ESCV) (weighted mean differences (WMD) = 2.52, 95% CI: 1.11 to 3.94, p < 0.0001). Adverse events were tolerable. TSA revealed that an improved effectiveness rate was indicated. CONCLUSION: Tuina might improve the effectiveness rate and ESCV scores in patients with CV. However, the level of all the available evidence was low, and larger-scale and well-designed RCTs should be encouraged.

The Effectiveness and Safety of Acupoint Catgut Embedding for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effectiveness and safety of acupoint catgut embedding therapy (ACET) in postmenopausal osteoporosis (PMOP). METHODS: Review of some databases from their inception to June 2018 and randomized controlled trials (RCTs) in which ACET with PMOP were included. Two researchers extracted and evaluated the information independently. Cochrane Collaboration's tool and Jadad scale were used to evaluate the quality of the studies. RevMan V.5.3.3 software was used to carry out the meta-analysis while trial sequential analysis (TSA) performed with TSA 0.9 software. RESULTS: 12 RCTs with 876 participants were included in this review. Meta-analysis showed that ACET alone was not superior to medication in effectiveness rate (RR= 1.11; 95% CI (0.89, 1.40); P=0.35) and E2 (SMD= 0.20; 95% CI (-0.17, 0.57); P=0.28; I 2 =20%) while ACET combining medication was more effective on the effectiveness rate (RR= 1.32; 95% CI (1.20, 1.46); P<0.000 01) and E2 (SMD= 1.24; 95% CI (0.63, 1.84); P<0.0001). Additionally, ACET combining calcium could increase the bone mineral density (BMD) of the L2~4 vertebrae and femur-neck [WMDL2~4 = 0.03; 95% CI (0.01, 0.05); P=0.003; and WMDFemur-neck = 0.07; 95% CI (0.03, 0.10); P = 0.0006], reduce TCM syndrome score [WMD = -1.85; 95% CI (-2.13, -1.57); P<0.000 01], improve patient's quality of life [WMDthree months = 6.90; 95% CI (3.90, 9.89); P<0.000 01; and WMDsix months = 12.34; 95% CI (5.09, 19.60); P=0.0009], and relieve pain [WMDVAS = -1.26; 95% CI (-1.66, -0.85); P<0.000 01; and WMDPain score = -2.59; 95% CI (-4.76, -0.43); P= 0.02]. The TSA showed that the effectiveness of ACET for PMOP was demonstrated accurately. CONCLUSIONS: ACET combining medication but not ACET alone is more effective than medication as comparison in the treatment of PMOP. As a novel treatment, ACET shows the potential of effectiveness and deserves further high quality of well-designed study.

Acupuncture for primary osteoporosis: A network meta-analysis of randomized controlled trials protocol.

BACKGROUND: A large number of randomized controlled trials (RCTs) have shown that acupuncture (ACU) has certain advantages over pharmacotherapies in the treatment of primary osteoporosis (POP). However, due to the diversity of ACU treatments, its relative effectiveness have not yet been studied and explained. Therefore, based on the network meta-analysis (NMA), this study will compare the differences in the efficacy of multiacupuncture in the treatment of POP, to provide a reference for clinical treatment. METHODS: We will search PubMed, MEDLINE, Embase, the Cochrane Library, China National Knowledge Infrastructure (CHKD-CNKI), WANFANG database (Chinese Medicine Premier), Chinese Biomedical Literature database (CBM), and VIP for relevant RCTs of ACU treatments for POP, from their inceptions to January 2019. STATA 15.0 and GEMTC software will be used to perform a NMA. The evidence will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the type 1 error rate will be assessed by trial sequential analysis (TSA). RESULTS: The results of this review will be submitted to a recognized journal for publication. CONCLUSION: This proposed systematic review will evaluate the different advantages of various types of ACU in the treatment of POP. REGISTRATION: PROSPERO (registration number CRD42019122724).