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 compare and analyze the changes of aggregation rate and routine parameters of platelets stored in temperature cycle, cold storage at 4 ℃ and oscillating storage at 22 ℃, so as to provide more experimental data for platelet preservation methods. METHODS: Blood samples were collected at 5 time points on the 1^st, 2^nd, 3^rd, 4^th and 6^th day after platelet cycling preservation at temperature, cold storage at 4 ℃, and oscillating storage at 22 ℃. Platelet maximum aggregation rate (MAR) and routine parameters including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and platelet-larger cell ratio (P-LCR) were detected. RESULTS: The platelet MAR of three groups showed a significant decrease trend with the preservation time, the fastest decrease was in the 22 ℃ group, the slowest was in the 4 ℃ group, and the temperature cycle group was between the two groups. On the 3^rd day of preservation, the platelet MAR in 4 ℃ group was still in the normal range (MAR>60%), while in temperature cycle group was about 50%, and in 22 ℃ group was the lowest. On the 4^th day of preservation, platelet MAR in all the three groups was lower than 50%, and that in temperature cycle group was significantly lower than in 4 ℃ group but higher than in 22 ℃ group (both P < 0.05). On the 6^th day of preservation, platelet MAR in the temperature cycle group was significantly lower than that in the 4 ℃ group ( P <0.05), but there was no statistically significant difference compared to 22 ℃ group (P >0.05). PLT values in the three groups were all significantly decreased with the preservation time extension, and were significantly lower than those in the early stage of preservation within 6 days (all P < 0.05). PDW in temperature cycle group had no significant change within 6 days of preservation, but MPV and P-LCR were significantly increased. MPV, PDW and P-LCR all decreased significantly in 4 ℃ group within 6 days of preservation but increased in 22 ℃ group. Under the same storage days, PLT value of temperature cycle group had no significant difference with that of 4 ℃ group and 22 ℃ group, while MPV, PDW and P-LCR values were significantly higher than 4 ℃ group but lower than 22 ℃ group (all P < 0.05). CONCLUSION The aggregation function and routine parameters changes of temperature circulating preserved platelets are between 4 and 22 ℃.
Humans ; Platelet Aggregation ; Blood Preservation/methods* ; Temperature ; Blood Platelets ; Platelet Count ; Mean Platelet Volume ; Cryopreservation/methods* ; Cold Temperature

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Objective To investigate the influencing factors for low anterior resection syndrome(LARS)at one year after ileostomy reversal in patients who have undergone radical resection for rectal cancer,and to inform clinical interventions.Methods A retrospective cohort study was conducted on 312 patients who successfully underwent ileostomy reversal after radical resection for rectal cancer between January 2023 and January 2024 at 3 tertiary hospitals in Chongqing.Based on LARS scores at 1-year after stoma reversal,they were divided into a LARS group(score≥21)and a non-LARS group(score≤20).Clinical data were collected from the medical record system,including age,body mass index(BMI),sex,tumor size,tumor distance from the anal verge,T stage,N stage,date of low anterior resection,neoadjuvant therapy,postoperative chemotherapy,anastomotic leakage,and date of ileostomy reversal.Univariate analysis was used to screen potential influencing factors,and variables with P<0.2 were included in a multivariate logistic regression model.Binary stepwise regression analysis was applied to further analyze significant influencing factors for LARS at 1 year after ileostomy reversal.Results In the cohort,there were 127 patients assigned into the LARS group and 185 into the non-LARS group.The incidence of LARS at 1 year after ileostomy reversal was 40.70%,with mild cases accounting for 21.79%and severe ones for 18.91%,and a mean LARS score of 14.52±11.64.Multivariate logistic regression analysis showed that neoadjuvant therapy(yes vs no:OR=1.830,95%CI:1.088～3.089;P=0.023),tumor distance from anal verge≤5 cm(vs>5 cm:OR=2.044,95%CI:1.249～3.374;P=0.005),occurrence of anastomotic leakage(yes vs no:OR=7.470,95%CI:2.247～34.102;P=0.003),time to reversal(≥181 d vs 91～180 d:OR=2.297,95%CI:1.363～3.917;P=0.002),and N stage(N1～N2 vs N0:OR=1.650,95%CI:1.009～2.717;P=0.047)were significant influencing factors for LARS at 1 year after ileostomy reversal.Conclusion Our results suggest that anastomotic leakage,time to reversal≥181 d,tumor distance from anal verge≤5 cm,neoadjuvant therapy,and N stage N1～N2 are associated with the occurrence of LARS at 1 year after ileostomy reversal in patients following radical resection of rectal cancer.Clinical healthcare providers should implement early intervention and long-term follow-up for patients with high-risk factors both before and after stoma reversal.

The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85％of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.