Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To evaluate the efficacy of transurethral resection of bladder tumor(TURBT)in treating cystitis glandularis(CG),and to explore the influencing factors.Methods A retrospective analysis was conducted on 243 CG patients treated with TURBT during Jan.2013 and Dec.2020 in our hospitals.Postoperative efficacy was assessed using global response assessment(GRA).The correlation between GRA score and the demographic characteristics,comorbidities,initial complaints,and postoperative recurrence was determined with logistic regression analysis.Results Among the 243 patients,3.70％(9/243)had dysplasia,2.47％(6/243)had exuberant hyperplasia of Brinell's nest,and 2.06％(5/243)had intestinal metaplasia.The mean GRA score was(2.02±0.72)after a follow-up of(47.10±28.53)months.Re-operation was performed in 10.29％(25/243)of the patients due to recurrence,and the improvement of hydronephrosis and dysuria was 70.59％(12/17)and 50.00％(15/30),respectively.Pelvic fat increase developed in 1 patient(0.41％)after surgery.Logistic regression analysis showed that postoperative GRA score was not significantly correlated with demographic characteristics,body mass index,comorbidities,alcoholism and postoperative recurrence(P＞0.05).Conclusion TURBT is an effective method in the treatment of CG,which can significantly improve patients'hydronephrosis and dysuria.However,approximately 10％of the patients experience recurrence,necessitating further surgery,which suggests the need for vigilance regarding potential recurrence during treatment.

Objective To observe the differences in the expression levels of the hypoxia-inducible factor-1α/heme oxygenase-1/vascular endothelial growth factor A (HIF-1α/HO-1/VEGF-A) signaling pathway under different maturation outcomes of arteriovenous fistula (AVF) in patients with stage 5 chronic kidney disease, and explore the regulatory mechanism of the HIF-1α/HO-1/VEGF-A signaling pathway in the maturation process of AVF. Methods A total of 45 patients with AVF surgery for stage 5 chronic kidney disease were selected as research objects, vascular specimens were collected during the AVF surgery, and the patients were divided into AVF maturation group (n=35) and AVF poor maturation group (n=10) based on the AVF maturation outcomes within 8 weeks after surgery. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression levels of HIF-1α, HO-1 and VEGF-A in the HIF-1α/HO-1/VEGF-A signaling pathway; the Western blotting was used to detect the protein expression levels of HIF-1α, HO-1 and VEGF-A; the enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of downstream inflammatory factors such as interleukin-1β (IL-1β), interleukin-8 (IL-8), and transforming growth factor-β (TGF-β). Results The expression levels of HIF-1α mRNA, HO-1 mRNA, and VEGF-A mRNA in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the protein expression levels of HIF-1α, HO-1 and VEGF-A in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the expression levels of IL-1β, IL-8 and TGF-β in the AVF maturation group were significantly lower than those in the AVF poor maturation group (P < 0.01). Conclusion The upregulation of the HIF-1α/HO-1/VEGF-A signaling pathway is conducive to the early maturation of AVF. The measurement of the expression levels of the HIF-1α/HO-1/VEGF-A signaling pathway has a certain predictive significance for the early maturation outcome of AVF.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective:To summarize the experience of facial nerve(FN) preservation in microsurgical treatment of vestibular schwannoma (VS) resection via suboccipital retrosigmoid approach and to analyze the influencing factors of facial function prognosis in short-term and long-term period.Methods:Patients with VS who underwent microsurgery via suboccipital retrosigmoid approach by the skull base surgery team in Huashan Hospital from January 2013 to February 2018 were enrolled. A total of 308 patients were included in this study, including 132 males and 176 females. The average age was 47.9 year-old (Range: 17-79 year-old). The patient′s clinical data and FN function prognosis were recorded. Univariate and multivariate analysis by SPSS 23.0 statistical software were performed to evaluate the factors affecting facial function prognosis and its recovery.Results:Gross total resection was achieved in 304 cases, and subtotal resection was in 4 cases. The facial nerve preservation rate anatomically was 99.4%. The facial nerve of 2 cases was thin due to large tumor compression and severed, and a one-stage reconstruction was performed during surgery.Of the 308 patients, 300 cases were successfully followed up, and 8 cases were lost to follow-up. The mean follow-up time was 52 months. In short-term (2 weeks after surgery), satisfactory facial nerve function (House-Brackmann (H-B) grade Ⅰ-Ⅱ) was achieved in 96 cases, and 212 cases were unsatisfactory function (H-B grade Ⅲ-Ⅵ). After 1 year, 198 were satisfactory function and 97 were unsatisfactory. After 3 years, 219 were satisfactory function and 75 were unsatisfactory. Five years later, 155 were satisfactory function and 34 were unsatisfactory. According to the results of logistic regression analysis, the impact factors of FN function in short-term were tumor size ( P=0.011) and stimulation threshold (ST) of EMG monitoring ( P<0.001). The impact factors in long-term were tumor size ( P=0.005), ST of EMG monitoring ( P=0.005) and FN rehabilitation training. Conclusions:Tumor diameter is an independent factor related to FN function, and the larger the tumor, the worse the postoperative FN function. The ST of EMG (ST≤0.05 mA) can predict short-term and long-term FN function. The systematic facial rehabilitation training can effectively promote the recovery of FN after surgery.

OBJECTIVE: To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children. METHODS: The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared. RESULTS: A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G⁺), the most common multi-drug resistant G⁺ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G^- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011). CONCLUSIONS The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.
Humans ; Child ; Shock, Septic ; Retrospective Studies ; Sepsis ; Risk Factors ; Bacteria ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Escherichia coli ; Anti-Infective Agents ; Agranulocytosis

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal