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 gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveTo investigate the novel post-translational modifications (PTMs) of SnRK2.6, a central component in the abscisic acid (ABA) signaling pathway, such as SUMOylation, and to establish a foundation for revealing the physiological functions and molecular mechanisms of SnRK2.6 regulated by these new modifications. MethodsThe interaction between SnRK2.6 and the SUMO E3 ligase SIZ1, as well as members of the SUMO protease family, was examined using yeast two-hybrid and in vitro pull-down assays. An in vitro SUMOylation system in Escherichia coli was utilized to determine whether SnRK2.6 undergoes SUMOylation. Mass spectrometry, combined with site-directed mutagenesis of candidate lysine residues, was employed to identify potential SUMOylation sites on SnRK2.6. In vitro de-SUMOylation assays were performed to assess whether SUMO proteases interacting with SnRK2.6 could catalyze the removal of SUMO moieties from modified SnRK2.6. The protein stability of SnRK2.6 was assessed in a cell-free degradation assay using bacterial-purified SnRK2.6 incubated with total protein extracts from Col and siz1 mutant seedlings. To dissect the genetic relationship between SnRK2.6 and SIZ1, stomatal aperture assays were performed under ABA treatment using snrk2.6, siz1, and snrk2.6 siz1 double mutant plants. ResultsSnRK2.6 physically interacts with SIZ1 and the SUMO protease ESD4, with the binding domains localized to the C-terminal region of SIZ1 and the N-terminal region of ESD4, respectively. SnRK2.6 was found to be SUMOylated, exhibiting two distinct high-molecular-mass bands ranging from 70 to 100 ku, indicative of modified forms. Bioinformatics analysis predicted four putative SUMOylation sites on lysine residues K57, K63, K142, and K190. Mass spectrometry identified three SUMOylation sites on K63, K142, and K174. However, individual or combinatorial point mutations on these sites had minimal impact on the pattern or intensity of SUMOylation signals, suggesting that these residues may not be responsible for the SUMOylation on SnRK2.6. Instead, such mutations only weaken the protein stability or accelerate the protein mobility of SnRK2.6. Therefore, the exact SUMOylation sites on SnRK2.6 remain unidentified. In de-SUMOylation experiments, incubation of GST-ESD4 with SUMOylated SnRK2.6 for 1-2 h led to the near-complete disappearance of both SUMOylated bands. In contrast, neither the GST control nor the catalytically inactive mutant GST-ESD4^C448S exhibited any de-SUMOylation activity. In protein turnover experiments, SnRK2.6 exhibited markedly enhanced half-life in siz1 compared with Col, indicating that SIZ1-dependent SUMOylation promotes SnRK2.6 turnover. Phenotypically, snrk2.6 mutants were completely insensitive to ABA-induced stomatal closure; siz1 mutants displayed pronounced hypersensitivity; and the snrk2.6 siz1 double mutant phenocopied snrk2.6—showing no significant response to ABA beyond that of the snrk2.6 mutant. These data indicate that SIZ1 acts as a negative regulator of ABA-triggered stomatal closure and SnRK2.6 functions as a positive regulator, and the inhibitory activity of SIZ1 is strictly dependent on SnRK2.6, placing SnRK2.6 genetically upstream of SIZ1 in the ABA signaling pathway. ConclusionSnRK2.6 undergoes SUMOylation, although the specific SUMOylation sites have not been defined. SnRK2.6 is dynamically regulated by reversible SUMOylation—catalyzed by SIZ1 and reversed by ESD4—which controls its protein stability. SUMOylation acts as a destabilizing signal for SnRK2.6, and SIZ1 exerts its negative effect on ABA-triggered stomatal closure probably through promoting SnRK2.6 degradation via SUMOylation. These findings uncover SUMOylation as a critical regulatory layer fine-tuning SnRK2.6 abundance in ABA signaling.

OBJECTIVE: To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification. METHODS: Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg·d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β -protein 1-42 (A β_1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). RESULTS: A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and A β_1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01). CONCLUSIONS DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Male ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Brain/drug effects* ; Metabolomics ; Mice, Inbred C57BL ; Neuronal Plasticity/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cyclic AMP/metabolism* ; Reactive Oxygen Species/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Mice ; Amyloid beta-Peptides/metabolism* ; Signal Transduction/drug effects* ; Alzheimer Disease/drug therapy* ; Superoxide Dismutase/metabolism*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

OBJECTIVE: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional

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

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Objective:To explore the effect of kidney-strengthening and blood stasis-eliminating formula on nutritional status and quality of life in patients with osteoporosis combined with hemodialysis.Methods:From January 2024 to January 2025,60 patients with liver and kidney yin deficiency and blood stasis obstruction were selected from the Pizhou City Traditional Chinese Medicine Hospital's Hemodialysis Center.60 patients were randomly divided into two groups,30 in each group.The matched group received general treatment plus paricalcitol,while the treatment group received the same treatment plus Yishen Zhuyu Fang(a traditional Chinese medicine formula for kidney and blood stasis).The treatment course lasted 12 weeks.Changes in TCM syndrome scores,the Modified Subjective Global Assessment(MQSGA),the Kidney and Life Quality(KDQOLTM-36)scale,lipid levels,and nutritional indicators were compared before and after treatment.Results:After treatment,the TCM syndrome scores in both groups decreased(P＜0.05),with a more pronounced decrease in the treatment group(P＜0.05).The KDQOLTM-36 score in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05),indicating that the treatment group performed better than the matched group(P＜0.05).Both groups experienced a decrease in the MQSGA score(P＜0.05),although the difference was not statistically significant(P＞0.05),the treatment group showed a more noticeable decline.The TC,TG,LDL,and TG/HDL levels in the treatment group all decreased significantly,while HDL levels increased(P＜0.05).In contrast,the TC and HDL levels in the matched group did not change(P＞0.05),while the TG,LDL,and TG/HDL levels increased(P＜0.05).The treatment group performed significantly better than the matched group(P＜0.05).The TRF,Hb,and ALB levels in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05).The total effective rate of the treatment group was 90％,higher than the matched group(23.3％)(P＜0.05).Conclusion:The formula of tonifying the kidney and removing stasis can improve the nutritional status and quality of life of patients with liver and kidney yin deficiency and blood stasis obstruction in hemodialysis combined with osteoporosis.

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.