This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

A 10-year-old girl was admitted with a 38-hour history of widespread subcutaneous petechiae and hematuria and a 6-hour history of jaundice and oliguria. Physical examination revealed widespread subcutaneous petechiae and jaundice of the skin and sclera. Laboratory tests showed anemia, thrombocytopenia, acute kidney injury, and markedly elevated lactate dehydrogenase. Thrombotic microangiopathy was initially diagnosed, with a high suspicion of atypical hemolytic uremic syndrome (aHUS). Eculizumab was initiated within 9 hours of admission (within 48 hours of onset). After the first infusion, hemolysis rapidly ceased, and the platelet count and renal function gradually returned to normal. Whole-exome sequencing identified homozygous deletions of CFHR1 exon 2 and CFHR4 exon 1. aHUS typically has abrupt onset and rapid progression. Clinicians should maintain high suspicion for aHUS when the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury is present. Ultra-early eculizumab (within 48 hours of onset) rapidly blocks complement-mediated thrombotic microangiopathy, reverses organ injury, and improves long-term prognosis. Additionally, complement-related genetic testing is important for etiological clarification and individualized determination of eculizumab treatment duration.
Humans ; Antibodies, Monoclonal, Humanized/administration & dosage* ; Female ; Atypical Hemolytic Uremic Syndrome/drug therapy* ; Child ; Complement C3b Inactivator Proteins

Objective To investigate the association between gastroesophageal reflux disease(GERD)and the risk of incident chronic obstructive pulmonary disease(COPD)and explore potential effect modifiers influencing this association.Methods Clinical data from 476 175 participants in the UK Biobank(2006-2010)were collected.A Cox proportional hazards model was used to assess the relationship between GERD and the risk of incident COPD.Subgroup analyses were conducted to examine potential modifiers of the primary findings.Results A total of 11 587(2.43%)new COPD cases were diagnosed.The Cox proportional hazards model revealed that GERD was associated with an increased risk of incident COPD(HR=1.59,95%CI=1.46-1.74,P<0.001).GERD was linked to a higher risk of incident COPD in individuals aged<60 years(P<0.001)and non-smokers(P=0.011).No association was observed between GERD and the risk of incident COPD in current smokers with a daily cigarette consumption<10 cigarettes(P=0.261).Conclusion GERD may increase the risk of incident COPD.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Gastroesophageal Reflux/epidemiology* ; Middle Aged ; Proportional Hazards Models ; Incidence ; Male ; Risk Factors ; Female ; Aged

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective:The purpose of this study is to explore in depth the mechanism of the impact of brain drain on organizational cohesion,with a view to cracking the vicious circle problem caused by brain drain in the northeast region and eliminating the unfavorable factors affecting the core cohesion of public health institutions.Methods:A combination of convenience sampling and snowball sampling was used to survey11 912 valid questionnaires,and the data were systematically analyzed using descriptive statistics,regression analysis,and moderated mediated effects analysis.Results:Brain drain has a significant negative effect on organizational cohesion(β=-1.29,P<0.001);and role overload partially mediates between the two,with a significant mediating effect(effect value=-0.56,95%CI=-0.67～-0.46),and the indirect effect accounts for 43.4%of the total effect;and monthly income significantly moderates the effect of brain drain on organizational cohesion through role overload(β=1.00,P<0.001).Conclusion:It is recommended to alleviate the sense of role overload among public health personnel by adjusting the level of salary and benefits,and to reduce the negative impact of brain drain by adopting long-term incentive mechanisms and other strategies,thus enhancing organizational cohesion and providing theoretical and practical guidance for relevant institutions.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Objectives:The goal of the present study was to develop and validate a set of Mandarin Chinese adaptation of AzBio sentence test (CMnBio) used for the assessment of speech recognition in hearing-impaired listeners and cochlear implant (CI) users.Methords:Following the procedures of development of the English AzBio sentence materials, the present study was conducted in two stages. In the first stage, a total of 1 850 sentences were compiled and recorded by four Mandarin-speaking adult talkers (two males and two females), from which 1 020 sentences with better sound quality and higher naturalness were retained. All the 1 020 sentences were processed through a 5-channel noise vocoder and presented to 17 normal-hearing Mandarin-speaking adults for recognition. A total of 600 sentences (150 from each talker) in the range of approximately 62% to 92% correct were subsequently selected to compile 30, 20-sentence lists. In the second stage, 30 postlingually-deafened adult CI users were recruited to verify the list equivalency. Finally, the binomial distribution model was adopted to account for the inherent variability in the lists and to generate the lower and upper limits of the 95% critical differences.Results:The average sentence recognition of the 5-channel vocoder-processed 30 lists of Mandarin Chinese AzBio sentences (600 sentences total) by the 17 normal-hearing listeners was 78.0% correct. The validation based on the performance scores of the 30 CI participants revealed that 26 of the 30 lists were equivalent through a repeated-measures analysis of variance and a following post hoc Tukey′s test. The binomial distribution modelling indicated that the inter-list variability could be accounted for with a 65-item binomial distribution model. The lower and upper limits of the 95% critical differences for one-and two-list recognition scores were generated.Conclusions:The Mandarin Chinese adaptation of AzBio sentence test (CMnBio) is developed and validated for speech recognition assessment of CI users. The final set of 26, 20-sentence lists shows high inter-list reliability or equivalency. The elevated level of difficulties of the CMnBio sentences can help eliminate the ceiling effects when testing sentence recognition in Mandarin-speaking CI users. The lower and upper limits of the 95% critical differences derived from the binomial distribution modelling can provide guidance for detection of a significant difference in recognition scores in clinical settings.

OBJECTIVE: To explore the clinical characteristics of hospitalized patients with hematologic diseases complicated with carbapenem-resistant organisms (CRO) infection and analyze the risk factors of 30-day all-cause mortality. METHODS: The clinical data and laboratory test data of 77 hospitalized patients with hematologic diseases complicated with CRO infection in department of hematology of the Third Hospital of Shanxi Medical University from January 2015 to December 2020 were retrospectively analysed, the risk factors of 30-day all-cause mortality after CRO infection were analyzed by multivariate logistic regression. RESULTS: Among the total of 77 patients with hematologic diseases complicated with CRO infection, 29 died and 48 survived within 30 days of infection, with a case fatality rate of 37.66%. A total of 93 strains of CRO were isolated from these patients, of which Acinetobacter baumannii had the highest detection rate (25.81%, 24/93), followed by Pseudomonas aeruginosa (18.28%, 17/93). The lung was the most common site of CRO infection. The detected pathogens were highly resistant to carbapenems, and 64.52% (60/93) of the pathogens were resistant to imipenem with minimum inhibitory concentration (MIC)≥16 μg/ml. The results of the univariate analysis showed that albumin concentration <25 g/L (P =0.048), serum creatinine concentration≥120 μmol/L (P =0.023), age-adjusted Charlson comorbidity index (ACCI) (P =0.037) and primary treatments (supportive treatment, immunosuppressive therapy, chemotherapy, HSCT) (P =0.048) were significantly associated with 30-day all-cause mortality after infection. The results of multivariate logistic regression analysis showed that when CRO infection confirmed, albumin concentration <25 g/L (P =0.014, OR=6.171), serum creatinine concentration≥120 μmol/L (P =0.009, OR=10.867) were independent risk factors for 30-day mortality of patients with hematologic diseases complicated with CRO infection. CONCLUSION The mortality rate of CRO-infected patients with hematologic diseases is high. The detected pathogenic bacteria are highly resistant to imipenem. The albumin concentration <25 g/L and the serum creatinine concentration≥ 120 μmol/L at diagnosis of CRO infection were independent risk factors for 30-day mortality of the patients with hematologic diseases.
Humans ; Carbapenems/pharmacology* ; Retrospective Studies ; Creatinine ; Hematologic Diseases ; Risk Factors ; Imipenem ; Albumins

Aim To study the anti-inflammatory activ¬ity of diterpenes from Tripterygium wilfordii on lipopo- lysaccharide ( LPS)-induced macrophage and its mech¬anism. Methods MTT assay was used to detect the cytotoxicity of compounds. The Griess method was used to detect the NO on LPS-induced RAW264. 7 cells. ELISA was applied to determine the contents of inter- leukin 6 (IL-6) , tumor necrosis factor a ( TNF-a ) , interleukin lp (IL-lfj) and interleukin 18 (IL-18) in cell culture supernatant. Western blot was used to de¬tect IkBcx, .INK, ERK, p38, STAT3 and their phos-phorylation in LPS-induced RAW264.7, as well as the effect on COX-2, iNOS, NLRP3, caspase-1 , cleaved- caspase-1. Flow cytometry was employed to detect the effects of compounds on the phagocytosis of RAW 264. 7 cells. Results Hypoglicin II (1) and ent-pimara-8 (14) , 15-diene-19-ol (6) , two diterpenoid compounds from Tripterygium wilfordii could effectively inhibit the expression of inflammatory mediators ( COX-2 and iN- OS) and inflammatory cytokines (IL-6, IL-lp, IL- 18) in LPS-induced RAW264. 7 cells. Further re¬search found that the phosphorylation of IkBcx , JNK, ERK, P38, STAT3 and NLRP3 was all inhibited; however, there was no significant effect on the expres¬sion of IkBcx, JNK, ERK, P38 and STAT3. At the same time, they also inhibited the phagocytosis of mac-rophages. Conclusions The anti-inflammatory mecha¬nism of Tripterygium wilfordii diterpenoids 1 and 6 might be through inhibiting the production of NLRP3 inflammatory bodies, inflammatory mediators (COX-2 and iNOS) and inflammatory cytokines (IL-6, IL-lp and IL-18) , which is closely related to inhibiting the activation of MAPK, NF-kB and STAT3 pathway.