Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Objective:To analyze the associated factors and cumulative effects of cardiometabolic multimorbidity (CMM) among residents in southern Xinjiang.Methods:A stratified random cluster sampling method was used to conduct questionnaire surveys, physical examinations and laboratory tests among the personnel of the 51st Brigade, 3rd Division, Xinjiang, in 2016. The multivariate logistic regression, multivariate linear regression, restricted cubic spline, and network analysis methods were used to study the association of lifestyle (smoking, alcohol consumption and physical activity), socioeconomic (occupation, education and marital status) and clinical factors (waist circumference, body mass index and family history) with CMM.Results:A total of 12 773 study subjects were included. The prevalence of cardiovascular metabolic diseases among residents in southern Xinjiang was 52.49%. Specifically, the prevalence rates of dyslipidemia, hypertension, coronary heart disease, diabetes, and stroke were 31.14%, 29.95%, 6.78%, 6.26%, and 2.47%, respectively, and the prevalence of CMM was 19.06%. Multivariate logistic regression analysis revealed that the associations between clinical and socioeconomic factors and CMM significantly increased with higher scores. Specifically, the OR rose from 1.75 (clinical factors) and 1.07 (socioeconomic factors) on a score of 1 to 4.41 and 1.93 on a score of 3, respectively. The association between lifestyle factors and CMM was only observed at higher scores ( OR=1.26, 95% CI:1.07~1.62). The trend test using the scores of each group as continuous variables in the model showed that the risk of disease increased with the accumulation of clinical, socioeconomic and lifestyle factors (all P<0.05). Restricted cubic spline analysis demonstrated a non-linear relationship between the total number of associated factors and CMM ( Poverall<0.05 and Pnon-linear<0.05). Network analysis identified hypertension (strength=0.42) as the “core node” among the five diseases. When analyzing the three types of influencing factors, hypertension (strength=0.68), dyslipidemia (strength=0.47), coronary heart disease (strength=0.37), and clinical factors (strength=0.53) emerged as “core nodes”. In the network of nine associated factors, abnormal waist circumference and BMI (strength=0.90 and 0.84) were identified as “key factors”, while hypertension (strength=0.68) and dyslipidemia (strength=0.52) were identified as “key diseases”. Conclusion:The prevalence of CMM among residents in southern Xinjiang is high, and there is a cumulative effect of multiple factors. Hypertension and dyslipidemia are key diseases in the multimorbidity network, while abnormal BMI and waist circumference are key associated factors.

Antibody-drug conjugates (ADC) are one of the most popular types of anti-tumor drugs nowadays. Monomethyl auristatin E (MMAE), as a tubulin binder, is the most common applied payload in ADC and is also the main component that causes peripheral neuropathy (PN). By describing the clinical characteristics of 3 cases with MMAE ADC associated severe PN complications and analyzing reported references, this article summarizes that the occurrence of MMAE ADC associated PN is correlated with therapeutic cycles and duration of ADC, MMAE ADC associated PN is different from traditional chemotherapy-induced PN in the clinical presentation. Patients with MMAE ADC associated PN may present with a length-dependent involvement of peripheral motor and sensory nerves, and generally their weakness and deep sensory deficiency symptoms are more serious compared with traditional chemotherapy-induced PN. Two of the 3 patients achieved a relatively rapid recovery after treated with plasma exchange or immunoglobulin intravenous infusions.

Objective:A C57/BL6 mouse model of traumatic temporomandibular joint ankylosis (TTMJA) was established through composite trauma to lay the foundation for studying the pathophysiology of TTMJA.Methods:This study was conducted from January 2024 to February 2025. Forty-two 4-weeks old C57/BL6 mice, numbered 1 to 42, are randomly assigned to a control group ( n=21) and an experimental group ( n=21) using a computer-generated random number sequence. The experimental group undergoes modeling surgery on the left temporomandibular joint (TMJ), while the control group is routinely raised without special treatment. At 12 weeks post-surgery, the TMJ complex of both groups is assessed via body weight and mouth opening measurements, gross observation, micro-CT, and histological staining to evaluate model establishment. Results:At 12 weeks post-operation, in the experimental group, the body weight of mice [(27.75±1.08) g] did not show a significant difference compared with that of the control group [(30.80±0.29) g]( t=0.54, P=0.610). The maximum vertical passive mouth opening [(1.70±0.26) mm] in the experimental group was significantly lower than that in the control group [(3.43±0.21) mm]( t=8.92, P<0.001). Gross observation indicated that the right TMJ structure of the experimental-group mice was normal, while irregular hyperplasia occurred in the left TMJ complex. Micro-CT revealed that at 12 weeks post-operation, the right joint structure of the experimental-group mice was normal, with regular condyles and glenoid fossae. On the left side, a large amount of bone hyperplasia occurred on the lateral side of the joint in the condyles and glenoid fossae, forming two irregular bone masses, and there was an uncalcified radiolucent zone between the bone masses. In histological staining, no new cartilage or bone tissue was observed in the left joint space of the control-group mice, and the articular disc structure was normal. In the experimental-group mice, obvious new cartilage and calcified bone tissue were visible on the lateral side of the left joint space. A bone bridge was formed between the condyles and glenoid fossae, the articular disc structure disappeared, and bony ankylosis occurred. Conclusions:In this experiment, a TTMJA model of C57/BL6 mice was initially established by removing the articular disc and damaging part of the fibrous cartilage of the glenoid fossae and condyles, providing an experimental platform for further research on the pathogenesis of TTMJA.

In order to explore the effects of lipopolysaccharide(LPS)on the repair of bovine endo-metrial stromal cells(BESCs)during inflammatory response,BESCs were treated by LPS in this study.Cell apoptosis rate was detected using flow cytometry,cell viability was measured using the CCK-8 assay,cell migration ability was observed using a scratch assay,and the expression of con-nective tissue growth factor(CTGF),transforming growth factor-beta 3(TGF-β3)and vascular endothelial growth factor(VEGF)mRNA was measured using qRT-PCR.Additionally,the expression of key proteins in the PI3K/AKT and Wnt/β-catenin signaling pathways was assessed using Western blot analysis.The results showed that cell viability of BESCs significantly decreased(P＜0.01),cell migration ability decreased(P＜0.05),apoptosis rate of BESCs increased(P＜0.01),CTGF and TGF-β3 mRNA expression levels decreased(P＜0.01),while VEGF mRNA ex-pression increased after treatment with LPS(P＜0.01).The phosphorylation levels of PI3K,AKT and GSK-3β proteins decreased(P＜0.05),as well as the expression levels of c-Myc and Cyclin-D1 proteins also decreased(P＜0.01).These results indicated that LPS can inhibit the proliferation of BESCs and promote cell apoptosis possibly through the inhibition of the PI3K/AKT and Wnt/β-catenin signaling pathways.

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

OBJECTIVE: To compare clinical effect of arthroscopic double row fixation and single row fixation in treating Ideberg typeⅠA scapular glenoid fracture. METHODS: From June 2018 to December 2022, 26 patients with Ideberg typeⅠA scapular glenoid fracture treated with shoulder arthroscopy were divided into single-row anchor group and double-row anchor group according to the fixation method of fracture block. There were 12 patients in single-row anchor group, including 7 males and 5 females, aged from 25 to 53 years old with an average of (38.42±9.61) years old;the time from injury to operation ranged from 2 to 7 days with an average of (4.75±1.82) days. There were 14 patients in double-row anchor group, including 10 males and 4 females, aged from 21to 53 years old with an average of (37.36±10.19) years old;the time from injury to operation ranged from 1 to 8 days with an average of (4.21±2.01) days. The changes of shoulder joint flexion, abduction, lateral lateral rotation, Constant-Murley shoulder function score and Rowe scores were compared between two groups before operation and 1 year after operation. The percentage of bone mass in pelvis area before operation and the percentage of bone defect in pelvis area at the latest follow-up were compared between two groups. RESULTS: All patients were followed up for 12 to 15 months with an average of (13.08±1.17) months in single-row anchor group and 12 to 15 months with an average of (13.29±1.07) months in double-row anchor group, with no statistical significance between two groups (P>0.05). The results of anterior flexion, abduction and lateral lateral rotation in single-row anchor group were(86.67±6.62) °, (79.50±5.68) °, (38.17±1.70) ° before operation, and (162.50±4.52)°, (169.17±3.35)°, (50.67±10.20)° at 1 year after operation; while in double-row anchor group were (84.14±5.48) °, (81.71±5.20) °, (39.29±3.63) ° before operation and (162.29 ± 5.53) °, (167.14±3.61) °, (56.93±9.56) ° at 1 year after operation;the difference between two groups before operation and 1 year after operation was statistically significant (P<0.05). There were no significant difference between two groups (P>0.05). Constant-Murley scores and Rowe scores in single-row anchor group were (55.42±3.75), (43.75±18.49) before operation and (94.83±2.21), (95.42±4.50) at 1 year after operation, respectively;while in double-row anchor group were (54.50±7.88), (41.79±18.25) before operation and (94.36±4.73), (95.00±4.80) at 1 year after operation;there was no significant difference in Constant-Murley score and Rowe score between two groups before operation and 1 year after operation (P>0.05). There was significant difference in the percentage of bone mass in pelvis area between two groups before operation (P>0.05). There was no significant difference in the percentage of bone defect in the shoulder area between single-row anchor group(4.42±1.51)% and double-row anchor group (2.71±1.44)% at 1 year after operation (P<0.05). CONCLUSION Both single and double row fixation techniques for the treatment of Ideberg typeⅠA scapular glenoid fracture could receive satisfactory functional recovery. However, double-row fixation has more advantages in reducing bone resorption of fracture mass.
Humans ; Female ; Male ; Middle Aged ; Arthroscopy/methods* ; Adult ; Scapula/surgery* ; Case-Control Studies ; Fractures, Bone/physiopathology* ; Fracture Fixation, Internal/methods* ; Shoulder Joint/physiopathology* ; Range of Motion, Articular