[摘 要] 目的：探究聚丝蛋白（FLG）在黑色素瘤组织中的表达及其与患者临床病理特征、预后的关系。方法：选取2019年6月至2020年8月间山东第一医科大学附属人民医院收治的70例黑色素瘤患者为研究对象，取术中切除的瘤组织及瘤旁组织标本，用免疫组织化学法检测FLG蛋白表达，根据FLG的表达将患者分为阳性组和阴性组，比较瘤组织、瘤旁组织及不同病理特征下黑色素瘤组织中FLG的阳性表达率。随访患者3年，根据患者预后情况将患者分为生存组（n = 43）和死亡组（n = 27），比较两组患者的FLG阳性表达率，采用Kaplan-Meier法绘制生存曲线，比较两组患者生存时间。结果：黑色素瘤组织中FLG表达阳性率显著低于瘤旁组织（P < 0.05）；FLG阳性组肿瘤直径 > 1 cm、Breslow厚度 > 2 mm、局部溃疡、TNM分级Ⅲ～Ⅳ级、淋巴结转移、肿瘤侵袭占比显著低于阴性组（P < 0.05或P < 0.01）；70例患者中死亡27例，生存43例，生存率61.42%，死亡组患者FLG表达阳性率显著低于生存组（P < 0.05），FLG表达阳性患者生存时间显著长于阴性患者（P = 0.010）；多因素Cox回归分析显示，Breslow厚度 > 2 mm、TNM分级Ⅲ～Ⅳ级、淋巴结转移、肿瘤侵袭是影响黑色素瘤患者预后的危险因素（P < 0.01或P < 0.001），FLG表达阳性为保护因素（P < 0.01或P < 0.001）。结论：黑色素瘤组织中FLG显著降低，且与肿瘤Breslow厚度、分期侵袭和淋巴结转移等病理特征及预后有关。

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*

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*

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective To investigate the clinical value of thyroid globulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)in the diagnosis and treatment of papillary thyroid microcarcinoma(PTMC).Methods A total of 346 patients with thyroid nodules who underwent surgical treatment in the hospital from August 2012 to October 2021 were selected as the research objects.According to the postoperative pathologi-cal results,the patients were divided into the benign nodule group,PTMC group and non-micro papillary thy-roid carcinoma(PTC)group.The general data of the patients and thyroid function indexes[free triiodothyro-nine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),TgAb and TPOAb]before and after operation were collected,the tumor recurrence or lymph node metastasis after operation were ob-served,and the relationship between serum TgAb and TPOAb and the risk and prognosis of PTMC was ana-lyzed.Results The positivity rate of TgAb in the PTMC and non-micro PTC groups was significantly higher than that in the benign nodule group(P<0.05).The TPOAb positivity rate was not significantly different among the three groups(P>0.05).Only the TSH level in the PTMC group was higher than that in the non-micro PTC group(P<0.05).Multivariate logistic analysis showed that younger age,higher TSH and positive TgAb were independent risk factors for PTMC and non-micro PTC(P<0.05).However,the risk of PTC didn't increase with increasing TgAb titres.The positivity rate of TgAb in the PTMC and non-micro PTC groups didn't change significantly within one month after operation,but decreased in one year after operation(P<0.05).The TPOAb positivity rate decreased after operation,but the difference was not statistically sig-nificant(P>0.05).In the PTMC group,four cases had tumor recurrence or lymph node metastasis,and the TgAb level increased by 88.4%,49.5%,5.7%and 84.0%respectively when the tumor recurred or metasta-sized.Among them,the TPOAb level increased by 51.6%,30.0%and 2.9%respectively in three cases and decreased by 53.9%in one case.In the PTMC group,there were 11 patients with cervical lymph node enlarge-ment,and there was no statistical difference in TgAb and TPOAb levels when the condition changed(P>0.05).Conclusion TgAb is a risk factor for PTMC,and can be followed up regularly during the diagnosis and treatment of PTMC.The specificity of TPOAb is not as good as that of TgAb,and appropriate follow-up can be chosen during the course of the disease.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective:To analyze the clinical characteristics, imaging, myopathology and outcomes of patients with COVID-19 related autoimmune myopathy.Methods:The clinical features, serum creatine kinase (CK), myositis antibodies, muscle magnetic resonance imaging, myopathology and therapy of 5 patients with COVID-19 related autoimmune myopathy diagnosed in Peking University First Hospital from December 2022 to April 2023 were collected. The effects of the therapy after a short term follow up were analyzed.Results:Among the 5 patients, there were 3 males and 2 females, with onset age of 42-86 years. All patients presented with proximal muscle weakness in the recovery term of COVID-19. Myalgia was noted in 3 cases, dysphagia in 1, skin damage in 2, interstitial lung disease in 1. The serum CK of the 5 patients was 1 663-16 000 IU/L, 1 patient had anti-3-hydroxy-3-methylglutaryl-CoA reductase autoantibodies and 1 patient had anti-signal recognition particle autoantibodies. The electromyography showed myogenic lesions in all patients. Muscle magnetic resonance imaging showed diffuse muscle edema in all patients, myofascial edema in 3 and subcutaneous-tissue edema in 3. The muscle biopsies in 4 patients revealed necrotic myopathy,with high P62 expression in muscle fibers. The electromicroscopy of 2 patients revealed vacuolated mitochondria and intranuclear tubulofilamentous inclusions in muscle fibers. Four patients were treated with glucocorticoids, of whom 2 patients combined with intravenous immunoglobulin, tacrolimus or cyclophosphamide. One case had close monitoring without drug therapy. They showed significant improvement, but the CK was still abnormal in 4 patients.Conclusions:COVID-19 leads to immune mediated myopathy. The manifestation of patients is characterized by proximal predominant weakness and high creatine kinase level. Muscle magnetic resonance imaging shows diffuse muscle edema. The muscle biopsies reveal necrotic myopathy. The effectiveness of immunosuppression needs to be further studied.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.