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

Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility. This study investigated two novel homozygous SPAG17 mutations (M1: NM_206996.2, c.829+1G>T, p.Asp212_Glu276del; and M2: c.2120del, p.Leu707*) identified in four infertile patients from two consanguineous Pakistani families. These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa. Quantitative real-time polymerase chain reaction (PCR) of patients' spermatozoa also revealed a significant decrease in SPAG17 mRNA expression, and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella. However, no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients. Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls. Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17 (SPATA17), a component of the C1a projection, and sperm-associated antigen 6 (SPAG6), a marker of the spring layer, revealed disrupted expression of both proteins in the patients' spermatozoa. Altogether, these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme, expanding the phenotypic spectrum of SPAG17 mutations in humans.
Humans ; Male ; Infertility, Male/pathology* ; Sperm Tail/ultrastructure* ; Homozygote ; Microtubule-Associated Proteins/genetics* ; Axoneme/genetics* ; Spermatozoa/ultrastructure* ; Adult ; Mutation ; Sperm Motility/genetics* ; Pedigree ; Microtubules ; Microtubule Proteins/genetics*

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022.Methods:Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed.Results:A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024.Conclusion:The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

In recent years， the research data on the combination model of insomnia of liver depression and qi stagnation syndrome in traditional Chinese medicine （TCM） were sorted out and summarized in terms of the selection of experimental animals， modelling methods， and model evaluation， with a view to providing references for the standardized preparation of the experimental model of insomnia of liver depression and qi stagnation syndrome and the study of the intervention mechanism. As for the selection of experimental animals， rats and mice are commonly used for the study of sleep patterns in the insomnia model of liver depression and qi stagnation syndrome because their sleep patterns are similar to those of human beings； zebrafish is suitable for the study of sleep patterns in early development because of its high genetic homology； and rhesus macaques， common marmosets， and crab-eating monkeys are used for the study of highly complex sleep disorders because their physiological and behavioural characteristics are closer to those of human beings. In terms of modelling methods， electrical stimulation， chronic restraint， chronic emotional stress and impact psychological stress each have their own characteristics and application scenarios， while chronic tail-clamping stimulation combined with intraperitoneal injection of p-chlorophenylalanine （PCPA） combines physical and chemical stimuli， in order to simulate the complex mechanism of insomnia in human beings， and to more comprehensively simulate the pathology of insomnia with liver depression and qi stagnation syndrome. In terms of evaluation indexes， electroencephalography （EEG） and electromyography （EMG） monitoring and barbiturate synergistic sleep test are the most commonly used and scientific methods for evaluating insomnia animal models with liver depression and qi stagnation syndrome， which can provide intuitive and continuous sleep state monitoring； barbiturate synergistic sleep test can reflect the sensitivity and responsiveness of the model animals to the sleep-regulating medications； and the introduction of the method of using formulas to measure syndromes for the evaluating the model can combine the treatment and diagnostic principles of TCM with modern scientific research.

Objective:To analyze the specific immunoglobulin G (IgG) antibodies level in the population after the coronavirus disease 2019 (COVID-19) pandemic in Henan Province.Methods:A total of 5 178 peripheral venous blood samples were collected from 10 districts (counties) in Henan Province according to the national seroepidemiological survey program for COVID-19, and the method of cluster random sampling was adopted from March 6 to 15, 2023. Descriptive analysis was used for the basic data, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, SARS-CoV-2 infection of the respondents. The specific IgG antibody of SARS-CoV-2 was detected using chemiluminescence method. Statistical analysis was performed by using rank sum test, Kruskal Wallis test, and Dunn′s test.Results:The overall positive rate of SARS-CoV-2-specific IgG antibody was 83.35%(4 316/5 178). There were statistically significant differences in the specific IgG antibodies against SARS-CoV-2 produced by people of different sexes, different ages, infected or not, vaccinated or not, and vaccinated with different doses of SARS-CoV-2 vaccine ( Z=3.60, H=195.32, Z=6.10, 18.08, H=382.70, respectively, all P<0.001). The specific IgG antibodies produced by unvaccinated+ uninfected group, unvaccinated+ infected group, vaccinated+ uninfected group, and vaccinated+ infected group were 3.54(0.98, 11.00), 60.65(2.33, 84.80), 133.00(59.80, 173.00), and 142.00(98.30, 176.00), respectively. And the difference was statistically significant( H=354.62, P<0.001). The specific IgG antibodies of uninfected people increased with the increase of inoculum times( H=287.00 and 98.48, both P<0.001). The specific IgG antibodies of people who were not infected with SARS-CoV-2 in the groups of whose interval from the last inoculation of SARS-CoV-2 vaccine to blood collection was less than three months, three to six months and more than six months were 171.86(156.04, 196.57), 71.71(17.08, 110.38) and 132.14(57.59, 172.25), respectively, and the difference was statistically significant ( H=19.93, P<0.001). Among them, the absolute difference between the less than three months group and the three to six months group was statistically significant ( Z=3.67, P<0.001), and the absolute difference between the less than three months group and the more than six months group was statistically significant ( Z=3.47, P<0.001). The specific IgG antibodies level in the less than three months group was the highest. Conclusions:There is a certain correlation between the number of SARS-CoV-2 vaccine doses and the specific IgG antibodies level in uninfected people. The specific IgG antibodies could maintain a high level for three months after immunization.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To study the relationship between peripheral blood Toll like receptor 4(TLR4),interleukin-1β(IL-1β)and neutrophil-to-lymphocyte ratio(NLR)and the progression and prognosis of acute pancreatitis(AP).Methods A total of 250 patients with AP were divided into the mild group(121 cases),the moderately severe group(89 cases)and the severe group(40 cases)according to the disease severity.Patients were divided into the poor prognosis group(33 cases)and the good prognosis group(217 cases)based on the prognosis after 5 days of treatment.Peripheral blood levels of TLR4,IL-1β and NLR were compared at different time points,different conditions and different prognosis in patients.The correlation of peripheral blood levels of TLR4,IL-1β and NLR,Ranson score and amylase were analyzed by Pearson correlation analysis.The value of each indicator in the diagnosis of severe AP was analyzed using ROC curve,and multivariate Logistic regression analysis was conducted to identify the prognostic risk factors.Results TLR4,IL-1β and NLR levels in AP patients were higher 24 h after admission than 48 h and 72 h after admission(P＜0.05).Peripheral blood TLR4 and IL-1β levels in AP patients at 24 h after admission increased with the condition became worse.NLR level was higher in the severe group than that in the moderately group or the mild group(P＜0.05).Peripheral blood TLR4,IL-1β and NLR levels in AP patients 24 h after admission were positively correlated with Ranson score at 48 h after admission and amylase level at 24 h after admission(P＜0.05).The area under ROC curve,sensitivity and specificity of the combination of TLR4,IL-1β and NLR at 24 h after admission for predicting severe AP were 0.895,84.53%and 81.69%.Peripheral blood TLR4,IL-1β and NLR levels 24 h after admission were higher in the poor prognosis group than those in the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that elevated TLR4,IL-1β and NLR at 24 h after admission were independent risk factors for poor prognosis of patients with AP(P＜0.05).Conclusion Peripheral blood TLR4,IL-1β and NLR in patients with AP are closely related to disease progression and prognosis.Therefore,they can be taken as important monitoring indicators.

Objective:To analyze the genetic evolution and molecular characteristics of H7N9 avian influenza virus (AIV) isolated in a live poultry market.Methods:Samples such as poultry feces, sewage, and hair removal machine and chopping board swabs were collected. Real-time fluorescent quantitative PCR was used to detect influenza A virus and H7N9 AIV in the samples. The whole genome of H7N9 AIV was amplified with influenza A virus universal primers and sequenced. BLAST and MEGA X were used for sequence alignment, phylogenetic analysis and molecular characterization.Results:Seven poultry-related environment samples were collected in the live poultry market in Xuchang city in February 2023, and four were positive for H7N9 AIV. The whole genome sequences of three H7N9 AIV isolates were successfully obtained, and the isolates shared high nucleotide identity in different genes (98.37%-100.00%). BLAST analysis showed they were highly identical to H7N9 strains isolated from domestic poultry in China from 2020 to 2021. Genetic evolution analysis showed that the three isolates clustered in the same branch and were closer to the recent environmental isolates than to the recent strains isolated from human or avian. Through comparison with the sequences of the representative strains in different periods, it was found that the isolated strains in this study showed high avian pathogenicity with four amino acids KRAA inserted at the cleavage site; the hemagglutinin receptor-binding site was QSG, which was an avian binding receptor; there was a G186I mutation in hemagglutinin. Mammalian-adaptive mutation E627K was not detected in polymerase basic protein 2. Mutations (R292K and I38T) associated with drug resistance to neuraminidase inhibitor (oseltamivir) and polymerase acidic protein inhibitor (baloshavir) were not detected, suggesting that these isolates remained susceptible to these drugs. A S31N mutation was found in M2 protein, indicating they were resistant to alkamines.Conclusions:The three H7N9 AIV strains isolated in the live poultry market have high avian pathogenicity, but there are no significant increase in mutations related to the binding ability to human receptors, mammalian pathogenicity, viral transmissibility, or drug resistance as compared with previous representative strains causing human or avian infection.