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.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Aging is characterized by a gradual deterioration of the physiological integrity of cells,tissues,and or-gans,resulting in a decrease in the body's physiological functions and an acceleration of the onset of age-related diseases,ultimately leading to death.The aging of the liver,which is a critical metabolic organ,is closely linked to various chronic liver diseases,such as hepatitis,liver fibrosis,and cirrhosis,and it ex-acerbates their prognosis and is a primary risk factor for their development at all stages.Therefore,a comprehensive understanding of the causes,mechanisms,and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases.Stem cells,which are potential anti-aging agents,present a promising and effective alternative for managing liver aging.In this review,we systematically assess the driving factors,characteristics,and underlying mechanisms of liver aging.We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases.The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.

Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Objective To investigate the effect of fixation of posterior malleolar fractures of Haraguchi type Ⅱ on ankle function in trimalleolar fractures.Methods A total of 118 patients with trimalleolar fractures accompanied with posterior malleolar fractures of Haraguchi type Ⅱ who treated by surgery were selected as the study subjects,and divided into the fixation group(57 cases)and the non-fixation group(61 cases)based on whether the posterior malleolus was fixed during the operation.The operation related indicators,American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score,and the excellent and good rate of ankle function recovery were compared between the two groups.Results There was no significant difference in the operation time,intraoperative blood loss,hospital stay,fracture healing time,complete weight-bearing time or postoperative joint flatness between the two groups(P<0.05).At the end of the follow-up,the pain score and total score of the AOFAS ankle-hindfoot scale in the fixation group were higher than those in the non-fixation group,with statistically significant differences(P<0.05);and the excellent and good rate of ankle function recovery in the fixation group was higher than that in the non-fixation group,with statistically significant difference(P<0.05).Conclusion Surgical treatment for the trimalleolar fractures accompanied with posterior malleolar fractures of Haraguchi type Ⅱ can achieve satisfactory clinical outcome,and the fixation of posterior malleolar fractures of Haraguchi type Ⅱ can effectively reduce postoperative joint pain and improve ankle function.

Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.
Humans ; Female ; Middle Aged ; Adult ; Genetic Counseling ; Genetic Predisposition to Disease ; Breast Neoplasms/surgery* ; Ovarian Neoplasms/surgery* ; Mutation

Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.
Humans ; Female ; Middle Aged ; Adult ; Genetic Counseling ; Genetic Predisposition to Disease ; Breast Neoplasms/surgery* ; Ovarian Neoplasms/surgery* ; Mutation

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype