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.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

OBJECTIVE: To investigate the clinical efficacy and advantages of robot-assisted total knee arthroplasty (TKA) in patients with varus knee osteoarthritis. METHODS: Between October 2022 and June 2023, a total of 59 patients with severe knee osteoarthritis resulting in varus were treated with total knee arthroplasty, aged from 59 to 81 years with an average (70.90±4.63) years, including 19 mals and 40 females. The patients were divided into two groups based on the surgical method used:28 patients in the robot group and 31 patients in the traditional group. The robot group consisted of 8 males and 20 femalse patients, with an average age of (70.54±4.80) years and an average disease duration of (14.89±8.72) months. The traditional group consisted of 11 males and 20 females patients, with an average age of (71.39±4.5) years and an average disease duration of (12.32±6.73) months. The operative duration, amount of bleeding during the operation, postoperative activity time after the operation, hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and complications were compared between the two groups before and after the operation. Lateral tibia component (LTC), frontal tibia component (FTC), frontal femoral component (FFC) and lateral femoral component (LFC) were measured 6 months after operation Additionally, the degree of knee joint motility, American Knee Society score (KSS), and visual analogue scale(VAS) were compared before and after the operation. RESULTS: All patients had gradeⅠwound healing without any complications, and all patients were followed up for 6 to 8 months, with an average of (6.5±1.5) months. There were no significant differences preoperative imaging evaluation indexes (including HKA, LDFA, and MPTA), preoperative knee mobility, preoperative VAS, and preoperative KSS between the two groups (P>0.05). Comparing the operation time (109.11±7.16) min vs. (83.90±7.85) min, length of the incision (16.60±2.33) cm vs. (14.47±1.41) cm, intraoperative bleeding (106.93±6.15) ml vs. (147.97±7.62) ml, postoperative activity time (17.86±1.84) h vs. (21.77±2.68) h, between the two groups showed statistically significant differences (P<0.05). There were significant differences in FFC (88.96±0.84)° vs. (87.93±1.09)° and LFC (88.57±1.10)° vs. (87.16±1.2)° between the two groups at 6 months after operation (P<0.05). The robotic group 1, 3, 6 months after KSS (75.96±3.96), (81.53±3.78), (84.50±3.29) scores, VAS (3.68±0.67), (2.43±0.79), (0.54±0.64), knee joint mobility (113.32±4.72) °, (123.93±3.99) °, (135.36±2.34) °;Traditional group KSS (73.77±4.18), (76.48±3.60), (80.19±3.28) scores, VAS (4.16±1.04), (3.03±0.75), (1.42±0.76) scores, knee joint mobility (109.19±6.95) °, (119.94±6.08) °, (134.48±2.14) °. Compared to before surgery, both groups showed significant improvement in KSS, VAS and knee mobility during the three follow-up visits (P<0.001). Additionally, postoperative HKA (180.39±1.95)° vs. (178.52±2.23)°, LDFA (89.67±0.63) ° vs. (89.63±0.63)°, and MPTA (89.44±0.55)° vs. (89.29±0.60)° were significantly improved in both groups compared to before surgery (P<0.001). The robotic group had higher KSS than the traditional group at 1, 3, and 6 months after surgery (P<0.05). The robotic group also had lower VAS than the traditional group at 1, 3, and 6 months after surgery (P<0.05). Furthermore, knee mobility was higher in the robotic group than those in the traditional group at 1 and 6 months after surgery (P<0.05), but there was no significant difference between the two groups at 6 months after surgery. CONCLUSION Robot-assisted total knee arthroplasty is a safe and effective method for total knee replacement. The use of robotics can improve the limb axis and prosthesis alignment for patients with preoperative varus deformity, resulting in better clinical and imaging outcomes compared to the conventional group.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Middle Aged ; Osteoarthritis, Knee/physiopathology* ; Aged, 80 and over ; Robotic Surgical Procedures/methods*

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

This study was aimed at establishing a sensitive and specific sandwich ELISA detection method for Brucella.We screened monoclonal capture antibodies and detection antibodies for Brucella detection,and optimized and determined the opti-mal antibody coating time and concentration,as well as the optimal blocking solution,blocking time,and yin-yang critical val-ue.The specificity of this method was verified by examination of other bacteria prone to cross-reacting with Brucella.The sen-sitivity of the method was verified by detection of a gradient dilution of inactivated Brucella.Moreover,the sandwich ELISA detection results were compared with test tube agglutination and qPCR results.The selected capture antibody was 4A12,and the selected detection antibody was 6C12.Experimental analysis indicated that the optimal coating concentration for the 4A12 capture antibody was 5 μg/mL,and the optimal dilution ratio for the 6C12 detection antibody was 1∶2000.The optimal coating conditions were overnight at 4℃,and blocking with 5％skim milk powder for 2 hours.The established double antibody sand-wich ELISA method reacted with only Brucella but not other bacteria,thus demonstrating the method's good specificity.Inac-tivated Brucella solution was still detectable after dilution to 1 × 105 CFU/mL,thus demonstrating the method's good sensitiv-ity.The intra-and inter batch coefficients of variation were both below 10％,thus indicating the method's good repeatability.Thus,this study successfully established a dual antibody sandwich ELISA method for Brucella detection,which has good spe-cificity and sensitivity,and might provide an effective approach for the precise diagnosis and effective prevention and control of brucellosis.

Objective To investigate risk factors for the occurrence of an outbreak of surgical site infection(SSI)in the orthopedic department of a hospital.Methods Patients with SSI in the orthopedic department of a hospital in June-July 2017 were investigated,and the high-risk factors for infection were analyzed through case-control study.Specimens were taken from patients,health care workers(HCWs),environment and surgical devices for microbial detection.The homology between patients'and environmental isolates was analyze by pulsed-field gel electrophore-sis(PFGE).Results Staphylococcus aureus(S.aureus)were isolated from nasal secretion of four HCWs,including one doctor(D1)who was also isolated S.aureus from his forehead and hands.PFGE analysis found that S.aureus isolated from incision secretion of 2 patients were homologous to S.aureus isolated from the nasal cavity,forehead,and hands of doctor D1.Several targeted comprehensive infection control measures were implemented,including suspending sterile manipulation(such as surgery and dressing changes)of doctor D1;decolonization for all HCWs(including doctor D1)who carried S.aureus,requiring doctor D1 regularly trim nasal hair;strengthening the edu-cation and supervision of sterile manipulation and hand hygiene;implementing centralized isolation for SSI patients,et al.After timely implementation of the above comprehensive intervention measures,this SSI outbreak was effec-tively controlled in a short period of time.Conclusion Colonization of S.aureus in surgeons may lead to SSI in pa-tients,regular active screening and decolonization of surgeons involved in specific surgeries can be considered,and if necessary,nasal colonized people with dense nasal hair are required to regularly trim their nasal hair to reduce the occurrence of SSI.