Objective:To evaluate the effect of preoperative neoadjuvant chemotherapy on rocuronium bromide-induced neuromuscular blockade in patients undergoing radical resection of gastrointestinal tumors.Methods:In this retrospective cohort study, the medical records from patients pathologically diagnosed with gastrointestinal tumors (stageⅡ or Ⅲ) and underwent elective radical tumour resection under general anaesthesia, aged 43-74 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ at Shaanxi Provincial People′s Hospital from November 2021 to November 2022, were collected. The patients were divided into 2 groups based on whether preoperative neoadjuvant chemotherapy was performed: non-chemotherapy group and chemotherapy group. Non-chemotherapy group did not receive neoadjuvant chemotherapy before surgery and underwent direct surgery without receiving neoadjuvant chemotherapy. Chemotherapy group received 4 weeks of chemotherapy with FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), XELOX (capecitabine + oxaliplatin) or SOX (oxaliplatin + tegio) the three regimens before surgery. The neuromuscular monitoring was initiated after induction of intravenous anaesthesia, and rocuronium bromide 0.6 mg/kg was intravenously injected when the train-of-four ratio stabilized at 90%-110%. Mechanical ventilation was performed after endotracheal intubation when the train-of-four count was 0. When T 1 began to recover, rocuronium 0.2 mg/kg was intravenously injected, and rocuronium was intermittently injected during operation to maintain muscle relaxation. The onset time, complete muscle relaxation time, recovery index, 90% recovery index, maintenance time and consumption of rocuronium were recorded. Results:A total of 40 patients were finally included, with 20 in each group. Compared with non-chemotherapy group, the onset time was significantly prolonged, the recovery index, 90% recovery index and consumption of rocuronium were increased, the time for complete muscle relaxation was shortened ( P<0.05), and no significant change was found in the maintenance time of muscle relaxation in chemotherapy group ( P>0.05). Conclusions:Preoperative neoadjuvant chemotherapy can prolong the onset and recovery time of rocuronium, shorten the time to complete muscle relaxation and increase the consumption in patients undergoing radical resection of gastrointestinal tumors.

PURPOSE: Early mortality in major trauma has decreased, but MODS remains a leading cause of poor outcomes, driven by trauma-induced cytokine storms that exacerbate injuries and organ damage. METHODS: This prospective cohort study included 79 major trauma patients (ISS >15) treated in the National Center for Trauma Medicine, Peking University People's Hospital, from September 1, 2021, to July 31, 2023. Patients (1) with ISS >15 (according to AIS 2015), (2) aged 15-80 years, (3) admitted within 6 h of injury, (4) having no prior treatment before admission, were included. Exclusion criteria were (1) GCS score <9 or AIS score ≥3 for TBI, (2) confirmed infection, infectious disease, or high infection risk, (3) pregnancy, (4) severe primary diseases affecting survival, (5) recent use of immunosuppressive or cytotoxic drugs within the past 6 months, (6) psychiatric patients, (7) participation in other clinical trials within the past 30 days, (8) patients with incomplete data or missing blood samples. Admission serum inflammatory cytokines and pathophysiological data were analyzed to develop machine learning models predicting MODS within 7 days. LR, DR, RF, SVM, NB, and XGBoost were evaluated based on the area under the AUROC. The SHAP method was used to interpret results. RESULTS: This study enrolled 79 patients with major trauma, and the median (Q₁, Q₃) age was 51 (35, 59) years (52 males, 65.8%). The inflammatory cytokine data were collected for all participants. Among these patients, 35 (44.3%) developed MODS, and 44 (55.7%) did not. Additionally, 2 patients (2.5%) from the MODS group succumbed. The logistic regression model showed strong performance in predicting MODS. Ten key cytokines, IL-18, Eotaxin, MCP-4, IP-10, CXCL12, MIP-3α, MCP-1, IL-1RA, Cystatin C, and MRP8/14 were identified as critical to the trauma-induced cytokine storm and MODS development. Early elevation of these cytokines achieved high predictive accuracy, with an AUROC of 0.887 (95% CI 0.813-0.976). CONCLUSION Trauma-induced cytokine storms are strongly associated with MODS. Early identification of inflammatory cytokine changes enables better prediction and timely interventions to improve outcomes.
Humans ; Prospective Studies ; Middle Aged ; Male ; Female ; Adult ; Aged ; Cytokine Release Syndrome/etiology* ; Adolescent ; Young Adult ; Aged, 80 and over ; Wounds and Injuries/complications* ; Cytokines/blood* ; Multiple Organ Failure/diagnosis* ; Machine Learning

Objective:To develop and evaluate the reliability and validity of a questionnaire for assessing long-term care needs among community-dwelling older adults.Methods:Guided by the International Classification of Functioning, Disability and Health (ICF), an initial item pool for the questionnaire was constructed based on literature review, descriptive qualitative research, and expert consultations. The draft questionnaire was formulated by transforming the established indicator system for long-term care needs into survey items. Using stratified sampling, a total of 622 older adults from community settings in Changsha were surveyed between June and August 2021. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability testing were conducted.Results:The final questionnaire consists of three subscales (mental function, physical function, and activity and participation), comprising a total of 47 items. The item-level content validity index ( I- CVI) ranged from 0.830 to 1.000, and the scale-level content validity index ( S- CVI) was 0.915. EFA results showed that the extracted factors aligned well with the predefined dimensions after adjustment, with factor loadings exceeding 0.600 and cumulative variance contributions exceeding 70.000% for all subscales. CFA results indicated good model fit across all subscales and the overall questionnaire, confirming stable structural validity. The Cronbach's α coefficients ranged from 0.877 to 0.970, and test-retest reliability coefficients ranged from 0.901 to 0.957. Conclusions:The long-term care needs assessment questionnaire for community-dwelling older adults demonstrates strong reliability and validity, and can serve as a reliable tool for evaluating long-term care needs in this population.

Objective:To evaluate the effect of preoperative neoadjuvant chemotherapy on rocuronium bromide-induced neuromuscular blockade in patients undergoing radical resection of gastrointestinal tumors.Methods:In this retrospective cohort study, the medical records from patients pathologically diagnosed with gastrointestinal tumors (stageⅡ or Ⅲ) and underwent elective radical tumour resection under general anaesthesia, aged 43-74 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ at Shaanxi Provincial People′s Hospital from November 2021 to November 2022, were collected. The patients were divided into 2 groups based on whether preoperative neoadjuvant chemotherapy was performed: non-chemotherapy group and chemotherapy group. Non-chemotherapy group did not receive neoadjuvant chemotherapy before surgery and underwent direct surgery without receiving neoadjuvant chemotherapy. Chemotherapy group received 4 weeks of chemotherapy with FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), XELOX (capecitabine + oxaliplatin) or SOX (oxaliplatin + tegio) the three regimens before surgery. The neuromuscular monitoring was initiated after induction of intravenous anaesthesia, and rocuronium bromide 0.6 mg/kg was intravenously injected when the train-of-four ratio stabilized at 90%-110%. Mechanical ventilation was performed after endotracheal intubation when the train-of-four count was 0. When T 1 began to recover, rocuronium 0.2 mg/kg was intravenously injected, and rocuronium was intermittently injected during operation to maintain muscle relaxation. The onset time, complete muscle relaxation time, recovery index, 90% recovery index, maintenance time and consumption of rocuronium were recorded. Results:A total of 40 patients were finally included, with 20 in each group. Compared with non-chemotherapy group, the onset time was significantly prolonged, the recovery index, 90% recovery index and consumption of rocuronium were increased, the time for complete muscle relaxation was shortened ( P<0.05), and no significant change was found in the maintenance time of muscle relaxation in chemotherapy group ( P>0.05). Conclusions:Preoperative neoadjuvant chemotherapy can prolong the onset and recovery time of rocuronium, shorten the time to complete muscle relaxation and increase the consumption in patients undergoing radical resection of gastrointestinal tumors.

Objective:To develop and evaluate the reliability and validity of a questionnaire for assessing long-term care needs among community-dwelling older adults.Methods:Guided by the International Classification of Functioning, Disability and Health (ICF), an initial item pool for the questionnaire was constructed based on literature review, descriptive qualitative research, and expert consultations. The draft questionnaire was formulated by transforming the established indicator system for long-term care needs into survey items. Using stratified sampling, a total of 622 older adults from community settings in Changsha were surveyed between June and August 2021. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability testing were conducted.Results:The final questionnaire consists of three subscales (mental function, physical function, and activity and participation), comprising a total of 47 items. The item-level content validity index ( I- CVI) ranged from 0.830 to 1.000, and the scale-level content validity index ( S- CVI) was 0.915. EFA results showed that the extracted factors aligned well with the predefined dimensions after adjustment, with factor loadings exceeding 0.600 and cumulative variance contributions exceeding 70.000% for all subscales. CFA results indicated good model fit across all subscales and the overall questionnaire, confirming stable structural validity. The Cronbach's α coefficients ranged from 0.877 to 0.970, and test-retest reliability coefficients ranged from 0.901 to 0.957. Conclusions:The long-term care needs assessment questionnaire for community-dwelling older adults demonstrates strong reliability and validity, and can serve as a reliable tool for evaluating long-term care needs in this population.

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

Objective:To evaluate the relationship between hippocampal receptor-interacting protein kinase-1 (RIPK1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in postoperative neurocognitive dysfunction of aged rats with chronic knee arthritis pain.Methods:Sixty-four healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups ( n=16 each) using a random number table method: chronic knee arthritis pain group (group P), chronic knee arthritis pain+ operation group (group PS), RIPK1 inhibitor necrostatin-1+ chronic knee arthritis pain+ operation group (group NPS), and DMSO+ chronic knee arthritis pain+ operation group (group DPS). The knee arthritis model was prepared by intra-articular injection of monosodium iodoacetate (MIA) 1 mg into the left knee joint, and 12 weeks later exploratory laparotomy was performed under sevoflurane anesthesia. Necrostatin-1 6.25 mg/kg and the equal volume of DMSO were intraperitoneally injected at 1 h before operation in NPS group and DPS group, respectively. Thermal pain threshold was measured at 1 week before MIA injection and 6 and 12 weeks after MIA injection. Morris water maze test was used to evaluate the cognitive function at 7 days after surgery. Hippocampal tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the expression of RIPK1, phosphorylated RIPK1 (p-RIPK1), NLRP3, activated cysteine-aspartic protease caspase-1 (cl-caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot) and contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Thermal pain threshold was significantly decreased at 6 and 12 weeks after MIA injection as compared with that before injection ( P<0.05), and there was no significant difference in thermal pain threshold among the four groups ( P>0.05). Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was up-regulated, and the contents of IL-1β and IL-18 were increased ( P<0.05), and pathological changes of hippocampal neurons were marked in PS group, DPS group and NPS group. Compared with PS group and DPS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was down-regulated, the contents of IL-1β and IL-18 were decreased ( P<0.05), and pathological changes of hippocampal neurons were significantly attenuated in NPS group. Conclusions:Postoperative hippocampal RIPK1 function is enhanced in aged rats with chronic knee arthritis pain, which then activates NLRP3 inflammasomes, triggering neuroinflammation, and this process may be involved in the mechanism of postoperative neurocognitive dysfunction.

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)conditions. METHODS:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)assay.Briefly,2.5 μmol/L TubA was used with RAW264.7 cells under H/R condition.RAW264.7 cells were divided into three groups,namely the control,H/R,and TubA groups.The levels of reactive oxygen species(ROS)in the cells were detected using fluorescence microscopy.The protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western blotting.The levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA). RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1β and IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01). CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages subjected to H/R.This inhibition led to a decrease in the content of ROS in cells,which subsequently inhibited the activation of the NLRP3 inflammasome and the secretion of IL-1β and IL-18.

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)conditions. METHODS:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)assay.Briefly,2.5 μmol/L TubA was used with RAW264.7 cells under H/R condition.RAW264.7 cells were divided into three groups,namely the control,H/R,and TubA groups.The levels of reactive oxygen species(ROS)in the cells were detected using fluorescence microscopy.The protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western blotting.The levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA). RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1β and IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01). CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages subjected to H/R.This inhibition led to a decrease in the content of ROS in cells,which subsequently inhibited the activation of the NLRP3 inflammasome and the secretion of IL-1β and IL-18.

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)conditions. METHODS:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)assay.Briefly,2.5 μmol/L TubA was used with RAW264.7 cells under H/R condition.RAW264.7 cells were divided into three groups,namely the control,H/R,and TubA groups.The levels of reactive oxygen species(ROS)in the cells were detected using fluorescence microscopy.The protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western blotting.The levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA). RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1β and IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01). CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages subjected to H/R.This inhibition led to a decrease in the content of ROS in cells,which subsequently inhibited the activation of the NLRP3 inflammasome and the secretion of IL-1β and IL-18.