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.

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells,and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM).Methods:The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital.The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain(sFLC)ratio,next-generation sequencing(NGS)detection results,and its correlation with monoclonal plasma cells detected by flow cytometry(FCM)were further verified.The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected,and the distribution of plasma cell clusters in patients with different disease was observed.Results:The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis(RP)group,monoclonal gammopathy of undetermined significance(MGUS)group,smoldering multiple myeloma(SMM)group,HR-SMM group and multiple myeloma(MM)group;while the mean percentage of immature,primitive,reticular and flaming plasma cells were increased successively in the order of RP group,MGUS group,SMM group,and HR-SMM group,and the difference between any two groups was statistically significant(P＜0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2％of the total plasma cells.The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients(kappa=0.879 and kappa=0.891,both＞0.75),and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-(γ=0.825).The levels of non-involved immunoglobulin in IgG,IgA and IgM type HR-SMM patients were all decreased by more than 25％compared with the normal reference range,and the differences were statistically significant(P＜0.05).There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups(P＞0.05).Conclusion:In HR-SMM patients,the immature,primitive,reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells,and they are correlated with monoclonal plasma cells.The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.

OBJECTIVE: To investigate the clinicopathological features and prognosis of urinary bladder urothelial carcinoma (UBUC) with incidental prostate cancer (IPCa). METHODS: We retrospectively analyzed the clinicopathological features of 65 cases of UBUC and 38 cases of UBUC + IPCa after radical cystoprostatectomy (RCP) from January 2017 to February 2020. We compared their expressions of the immunohistochemical markers androgen receptor (AR) and (human epidermal growth factor receptor 2,HER2) between the two groups of patients, and analyzed their clinicopathological characteristics by chi-square test and their survival rates using the Kaplan-Meier method and log-rank test. RESULTS: The detection rate of UBUC + IPCa was 16.5%, and that of clinically significant IPCa was 39.5%, with preoperative PSA≥4 μg/L in 23.7% of the patients. Compared with the patients with UBUC, most of the UBUC + IPCa cases had no smoking history (73.8% vs 92.1%, P = 0.024), and fewer had histological variants (43.1% vs 10.5%, P = 0.003). The incidence rate of vascular invasion was significantly higher in the UBUC than in the UBUC + IPCa group (49.2% vs 21.1%, P = 0.005), and so was the rate of advanced cases (67.7% vs 31.6%, P<0.001). In comparison with the patients of the UBUC group, those of the UBUC + IPCa group showed remarkably higher expressions of AR (9.2% vs 31.6%, P = 0.004) and HER2 (43.1% vs 71.1%, P = 0.006). The mean overall survival time was longer in the UBUC + IPCa than in the UBUC group (48.8 mo ［95% CI: 2.5－42.6 mo］ vs 39.9 mo ［95% CI: 2.8－34.5 mo］), but with no statistically significant difference between the two groups (P = 0.608). CONCLUSION Standardized sampling of prostate samples after RCP helps to improve the detection rate of IPCa. Preoperative level of PSA is not a good predictor of IPCa. Few patients with UBUC + IPCa have a history of cigarette smoking, and the predominant histological type of the malignancy is high-grade invasive urothelial carcinoma, which is not significantly different from UBUC in prognosis. The expressions of HER2 and AR are significantly higher in UBUC + IPCa than in UBUC, suggesting that UBUC + IPCa may benefit from HER2- and AR-targeted therapy.
Humans ; Male ; Urinary Bladder Neoplasms/metabolism* ; Receptors, Androgen/metabolism* ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Receptor, ErbB-2/metabolism* ; Prognosis ; Middle Aged ; Aged ; Survival Rate ; Prostatectomy

Objective: To investigate the associations between neutrophil-to-lymphocyte ratio (NLR) and estimated glomerular filtration rate (eGFR) in patients with primary aldosteronism (PA). Methods: This study was a cross-sectional study. Consecutive patients diagnosed with PA and admitted to the Second Affiliated Hospital of Nanchang University from October 2017 to April 2022 were enrolled. General information, blood routine, renal function, and other clinical data of the patients were collected. Based on the median NLR of the enrolled patients, NLR-1·1.73 m^-2. Multiple linear regression and multivariate logistic regression models, smooth curve fitting and threshold effect exploration were used to analyze the relationship between NLR and eGFR in PA patients, and stratified analysis and interaction tests were used to evaluate potential variables that may affect the correlation between NLR and eGFR. Results: This study finally included 743 PA patients, aged (50.3±10.4) years, 42.9% (319/743) were female, and the median NLR was 2.3. After adjusting for sex, age, body mass index (BMI) and other factors, multiple linear regression analysis showed that high NLR was negatively correlated with eGFR (β=-4.9, P=0.008), and multivariate logistic regression analysis showed that high NLR was associated with low eGFR (OR=3.1, P=0.002). In the corrected smooth curve, NLR is U-shaped correlation with eGFR, and the inflection point is at NLR=3.5. When the NLR was<3.5, the eGFR decreased with the increase of NLR (corrected β=-4.7, P<0.001); When the NLR was≥3.5, the eGFR increased with the increase of NLR (corrected β=5.8, P=0.031). The results of stratified analysis showed that there was an interaction between the association of NLR and eGFR with the presence or absence of hyperlipidemia (P interaction=0.017), and the correlation between NLR and eGFR was stronger in PA patients with hyperlipidemia. Conclusion: In the PA patients, there is a U-shaped relationship between NLR and eGFR, and higher NLR is associated with lower eGFR. PA patients with elevated NLR should undergo additional screening for chronic kidney disease and receive related preventive interventions.
Humans ; Female ; Male ; Neutrophils ; Glomerular Filtration Rate ; Cross-Sectional Studies ; Lymphocytes ; Hyperaldosteronism/diagnosis* ; Hyperlipidemias

Age estimation based on tissues or body fluids is an important task in forensic science. The changes of DNA methylation status with age have certain rules, which can be used to estimate the age of the individuals. Therefore, it is of great significance to discover specific DNA methylation sites and develop new age estimation models. At present, statistical models for age estimation have been developed based on the rule that DNA methylation status changes with age. The commonly used models include multiple linear regression model, multiple quantile regression model, support vector machine model, artificial neural network model, random forest model, etc. In addition, there are many factors that affect the level of DNA methylation, such as the tissue specificity of methylation. This paper reviews these modeling methods and influencing factors for age estimation based on DNA methylation, with a view to provide reference for the establishment of age estimation models.
Humans ; DNA Methylation ; CpG Islands ; Forensic Genetics ; Neural Networks, Computer ; Linear Models ; Aging/genetics*

Objective: To investigate the associations between neutrophil-to-lymphocyte ratio (NLR) and estimated glomerular filtration rate (eGFR) in patients with primary aldosteronism (PA). Methods: This study was a cross-sectional study. Consecutive patients diagnosed with PA and admitted to the Second Affiliated Hospital of Nanchang University from October 2017 to April 2022 were enrolled. General information, blood routine, renal function, and other clinical data of the patients were collected. Based on the median NLR of the enrolled patients, NLR-1·1.73 m^-2. Multiple linear regression and multivariate logistic regression models, smooth curve fitting and threshold effect exploration were used to analyze the relationship between NLR and eGFR in PA patients, and stratified analysis and interaction tests were used to evaluate potential variables that may affect the correlation between NLR and eGFR. Results: This study finally included 743 PA patients, aged (50.3±10.4) years, 42.9% (319/743) were female, and the median NLR was 2.3. After adjusting for sex, age, body mass index (BMI) and other factors, multiple linear regression analysis showed that high NLR was negatively correlated with eGFR (β=-4.9, P=0.008), and multivariate logistic regression analysis showed that high NLR was associated with low eGFR (OR=3.1, P=0.002). In the corrected smooth curve, NLR is U-shaped correlation with eGFR, and the inflection point is at NLR=3.5. When the NLR was<3.5, the eGFR decreased with the increase of NLR (corrected β=-4.7, P<0.001); When the NLR was≥3.5, the eGFR increased with the increase of NLR (corrected β=5.8, P=0.031). The results of stratified analysis showed that there was an interaction between the association of NLR and eGFR with the presence or absence of hyperlipidemia (P interaction=0.017), and the correlation between NLR and eGFR was stronger in PA patients with hyperlipidemia. Conclusion: In the PA patients, there is a U-shaped relationship between NLR and eGFR, and higher NLR is associated with lower eGFR. PA patients with elevated NLR should undergo additional screening for chronic kidney disease and receive related preventive interventions.
Humans ; Female ; Male ; Neutrophils ; Glomerular Filtration Rate ; Cross-Sectional Studies ; Lymphocytes ; Hyperaldosteronism/diagnosis* ; Hyperlipidemias

Objective: To examine the preliminary effect of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis for the prevention of parastomal hernia after abdominoperineal resection for rectal cancer. Methods: This study is a prospective case series study. From June 2021 to June 2022, patients with low rectal cancer underwent laparoscopic abdominoperineal resection combined with extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis at the First Department of General Surgery, Shaanxi Provincial People's Hospital were enrolled. The clinical data and postoperative CT images of patients were collected to analyze the incidence of surgical complication and parastomal hernia. Results: Totally 6 cases of patient were enrolled, including 3 males and 3 females, aging 72.5 (19.5) years (M(IQR)) (range: 55 to 79 years). The operation time was 250 (48) minutes (range: 190 to 275 minutes), the stoma operation time was 27.5 (10.7) minutes (range: 21 to 37 minutes), the bleeding volume was 30 (35) ml (range: 15 to 80 ml). All patients were cured and discharged without surgery-related complications. The follow-up time was 136 (105) days (range: 98 to 279 days). After physical examination and abdominal CT follow-up, no parastomal hernia occurred in the 6 patients up to this article. Conclusions: A method of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis is established. Permanent stoma can be completed with this method safely. It may have a preventive effect on the occurrence of parastomal hernia, which is worthy of further study.
Male ; Female ; Humans ; Colostomy/methods* ; Rectus Abdominis ; Laparoscopy/methods* ; Incisional Hernia/surgery* ; Rectal Neoplasms/surgery* ; Hernia, Ventral/surgery* ; Surgical Mesh/adverse effects*