The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

Objective To explore the relationship between the characteristics of five circuits and six qi(shorten as Wuyun Liuqi)in the birth year of the patients with common tumors and the occurrence of common tumors,and to evaluate the potential value of the Wuyun Liuqi theory in modern epidemiological research of tumors.Methods Clinical information was collected from the SEER(Surveillance,Epidemiology,and End Results)database(1975-2020)and from the Department of Oncology,Huizhou Hospital of Guangzhou University of Chinese Medicine in the recent 3 years.The birth year of the patients with common tumors were converted into the Wuyun Liuqi elements of zhongyun(yearly circuit),guest qi,dominant qi and combination of circuit and qi.The correlation of the Wuyun Liuqi elements with the risk of various types of tumors was explored by LASSO regression analysis,monofactorial regression analysis and multivariate logistic regression analysis.Results(1)A total of 2 215 896 cases were enrolled in the study,of which 2 215 024 cases were from SEER database,1 158 019 being male(52.28%)and 1 057 005 being female(47.72%).The rest of 872 cases were from our hospital,including 527 males(60.44%)and 345 females(39.56%).Breast cancer,prostate cancer,lung cancer,colorectal cancer,gastric cancer and liver cancer were involved.(2)It was found that there was a significant correlation between some Wuyun Liuqi elements and the occurrence of specific types of tumors.For example,the occurrence of lung cancer was related to insufficient tuyun(earth-element in motion)while the occurrence of breast cancer was related to the year of insufficient shuiyun(water-element in motion),indicating that there may be a potential relationship between the Wuyun Liuqi elements at birth with the risk of tumors.Conclusion The preliminary findings of this study support the feasibility of applying the theory of Wuyun Liuqi in predicting the risk of various types of tumors.However,for the complicated relationship between the characteristics of Wuyun Liuqi and tumorigenesis,further research is needed to explore the mechanism behind it.To provide more evidence for the establishment of risk prediction models and the practical application of traditional Chinese medicine concept of preventive treatment of disease in tumor prevention and treatment,future research should cover a larger population sample and more detailed birth time,and take family history,geographical factors and environmental factors.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Purpose: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. Materials and Methods: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. Results: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. Conclusion The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. Tomitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. No-tably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

BACKGROUND: Human interleukin (IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes. It has been demonstrated extensive beneficial effects on various diseases; however, its role in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. METHODS: In vivo, DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts (CFs) specific hIL-37b overexpression mice (IL-37-Tg). In vitro, primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid. Cardiac function of the mice was assessed using echocardiography. Masson staining, immunofluorescence, western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins. RESULTS: In this study, we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis, as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice. The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose (HG) and palmitic acid (PA). Moreover, we also discovered that the presence of IL-37 increased the expression of SOCS3, a crucial regulator of JAK/STAT signaling, in DCM mice and HG and PA-treated CFs. Finally, the anti-fibrotic action of IL-37 in HG and PA-treated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated. CONCLUSIONS Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.