With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

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 investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

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 incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To analyse the effects of physical activity on neurocognitive function in children with autism spectrum disorder (ASD),so as to provide a theoretical basis and specific guidance for the clinical cognitive function rehabilitation practice of ASD children. Methods: Relevant literature on the effects of physical activity on neurocognitive function in children with ASD were searched in the China National Knowledge Infrastructure (CNKI), Wanfang, Web of Science, and EBSCO databases from their inception to March 2024 using specific subject terms. Information on authors, countries, publication dates, study populations, diagnostic criterion, interventions, measurement tools and study results were extracted postscreening. The methodological quality of the articles was assessed using the PEDro Scale, followed by a systematic review. Results: A total of seventeen articles and were included in the study and English literature, most of them were of good quality. The study included 10 randomized controlled trials, 4 quasiexperimental designs, and 3 preand posttest designs. The rehabilitative effects of physical activity on children with ASD were primarily observed in enhanced attention and executive function, as well as improvements in brain structure and function. Children with ASD showed varying cognitive effects in physical and skillbased programs, with skillbased activities like basketball and table tennis notably improving cognitive function. Conclusion Physical activity is an effective intervention that enhances cognitive abilities such as attention and executive function, as well as brain structure and function in children with ASD.

Objective:To investigate the clinical efficacy of percutaneous kyphoplasty (PKP) assisted by intuitive visual navigation orthopaedic surgery robot in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective analysis was conducted in Peking University Third Hospital from June 2021 to November 2022, 78 patients with OVCF were treated by the intuitive visual navigation orthopaedic surgery robot or freehand surgery with a "C" arm X-ray machine. According to the method of puncture, they were divided into robot group and freehand group. In the robot group, there were 36 cases, including 7 males and 29 females, aged 74.50±5.87 years, 32 cases of single vertebral fractures, 4 cases of double vertebral fractures, 1 case of T 8, 2 cases of T 10, 2 cases of T 11, 11 cases of T 12, 10 cases of L 1, 8 cases of L 2, 2 cases of L 3, 3 cases of L 4, and 1 case of L 5. Bone mineral density T value was -2.94±0.50; In the freehand group, there were 42 cases, including 9 males and 33 females, aged 72.86±8.84 years, 36 cases of single fracture and 6 cases of double fracture, 1 case of T 6, 2 cases of T 7, 3 cases of T 11, 9 cases of T 12, 8 cases of L 1, 9 cases of L 2, 5 cases of L 3, 6 cases of L 4, and 5 cases of L 5. Bone mineral density T value was -3.00±0.50. The effectiveness evaluation indexes of the two groups were compared, which included surgery duration, X-ray fluoroscopy times, hospitalization time, lumbar pain visual analogue scale (VAS), Oswestry disability index (ODI) and height of fractured anterior vertebrae (HFAV). Results:Both groups of patients successfully received surgical treatment. The mean operating time of the robot group was 33.44±2.50 min, which was significantly longer than that of the free hand group, which was 29.69±2.40 min ( t=6.491, P<0.001). Meanwhile, the intraoperative blood loss of the robot group was 3.54±0.89 ml, which was significantly less than that of the freehand group, which was 6.72±1.89 ml ( t=9.110, P<0.001). In terms of radiographic fluoroscopy times, the average of the robot group was 26.81±7.76 times, which was significantly less than the freehand group's 42.61±6.62 times ( t=9.294, P<0.001). The postoperative vertebral front edge height in the free hand group was 18.64±0.32 mm and in the robot group was 18.79±0.36 mm. The difference was not statistically significant ( t=2.673, P=0.067). All patients were followed up for 8.3±2.9 months (range, 6-13 months). The VAS scores of low back pain in the two groups at 1 day and 6 months after operation were significantly improved compared with those before operation ( P<0.05), and there was no significant difference between the two groups in VAS score after operation ( P>0.05). Six months after surgery, the ODI of the free hand group and the robot group were 11.67%±2.13% and 12.11%±2.33%, respectively. The ODI scores of the two groups were significantly lower at 6 months postoperative follow-up than that before surgery, and the postoperative follow-up at all had significant differences compared with that before surgery ( P<0.05), and there was no difference between the two groups in postoperative ODI scores ( P>0.05). No obvious bone cement leakage was found in all patients during operation. Conclusion:Compared with the traditional C-arm X-ray for PKP treatment of OVCF by free hand, intuitive visual navigation orthopedic robot can safely and effectively assist in the completion of the operation process, and has the advantages of less intraoperative blood loss, fewer fluoroscopy times.

Objective:To explore the feasibility and clinical efficacy of prone transpsoas lateral interbody fusion (PTP LIF) combined with posterior pedicle screw fixation for the treatment of lumbar degenerative diseases in the prone position.Methods:A total of 23 patients who underwent LLIF in the prone position at the First People's Hospital of Yunnan Province between March 2023 and October 2023 were retrospectively analyzed. The cohort comprised 9 males and 14 females, with a mean age of 55.5±8.8 years (range, 41-70 years). The clinical diagnoses included intervertebral disc herniation with endplate inflammation (3 cases), lumbar spinal stenosis (13 cases), lumbar spondylolisthesis (5 cases), and lumbar instability (2 cases). The surgical segments involved L 3, 4 (15 cases), L 4, 5 (6 cases), and L 3-L 5 (2 cases), with 21 cases involving a single segment and 2 cases involving double segments. The disc height and lumbar lordosis Angle before and after surgery were compared. Lower back pain was evaluated using the visual analogue scale (VAS), while lumbar spine function was assessed via the Oswestry Disability Index (ODI). Clinical efficacy was evaluated according to the modified MacNab criteria at the last follow-up. Results:All surgeries were successfully completed. The operation time was 120.2±21.4 min (range, 90-175 min), intraoperative blood loss was 131.1±40.8 ml (range, 60-200 ml), and the hospital stay was 6.2±1.6 days (range, 4-10 days). Follow-up was obtained for all 23 cases, with the follow-up time being 9.6±2.2 months (range, 6-13 months). One case of endplate damage occurred during surgery, two cases of transient psoas muscle weakness occurred postoperatively, and one case of lower limb pain and numbness was reported; no cases of wound infection or delayed healing were observed. The postoperative disc height improved compared to preoperative (6.8±1.9 mm; F=66.618, P<0.001). There was no statistically significant difference between 3 months postoperative (11.1±1.2 mm) and immediately postoperative (12.2±1.2 mm; P>0.05), but there was a statistically significant difference between the last follow-up (10.7±1.1 mm) and immediately postoperative ( P<0.05). The postoperative lumbar lordosis angle improved compared to preoperative (35.3°±5.4°; F=19.465, P<0.001), with no statistically significant difference between 3 months postoperative (44.1°±5.4°) and immediately postoperative (47.8°±6.6°; P>0.05), but there was a statistically significant difference between the last follow-up (43.2°±5.3°) and immediately postoperative ( P<0.05). The postoperative VAS score improved compared to preoperative (6.3±1.1 points; F=79.931, P<0.001), and the last follow-up (1.1±1.1 points) showed further improvement compared to 3 months postoperative (1.7±1.4 points; P<0.05). The postoperative ODI improved compared to preoperative (69.9%±7.4%; F=592.392, P<0.001), with 3 months postoperative (23.1%±3.1%) showing improvement compared to 1 month postoperative (29.2%±3.1%), and the last follow-up (17.5%±3.6%) showing further improvement compared to 3 months postoperative ( P<0.05). At the last follow-up, the modified MacNab criteria were: excellent in 16 cases, good in 5, fair in 2, with an excellent and good rate of 91% (21/23); 7 cases of cage subsidence were observed, with no cases of internal fixation loosening. Conclusion:PTP LIF combined with pedicle screw fixation for the treatment of lumbar degenerative diseases is safe and effective, with satisfactory short-term postoperative outcomes.

Brucellosis,a worldwide epidemic bacterial zoonotic infectious disease caused by bacteria of the genus Brucella,jeopardizes livestock production and poses a major threat to public health safety.Among the various components of Brucella,the outer membrane proteins play crucial roles as the primary immune and protective antigens.These proteins are closely asso-ciated with Brucella's virulence,regulation of the immune response,and ability to survive and multiply within host cells.This article summarizes recent research progress in the primary outer membrane proteins of Brucella,and offers a synthesized view of the current knowledge landscape.Understanding the antigenic characteristics of Brucella outer membrane proteins may sub-stantially contribute to the establishment of new diagnostic methods and the design of new vaccines,thus potentially leading to more effective prevention strategies against brucellosis.The review provides a reference for future studies and may aid in brucel-losis control efforts.