Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.

Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.

Objective:To investigate the incidence and risk factors of coma in patients with hypoglycemia (≤3.9 mmol/L).Methods:A retrospective study was conducted. Patients aged 20 years and older with blood glucose levels ≤3.9 mmol/L, and measured by emergency physicians from January 2020 to December 2022 were collected. Baseline patient data, clinical values collected on-site, and treatment outcomes were analyzed. The Glasgow Coma Scale (GCS) was used to determine if patients were comatose, with GCS ≤8 classified as the coma group and GCS >8 as the non-coma group. Further analysis was conducted on the resuscitated coma group to identify factors affecting patient recovery. Patients were divided into eight age groups, seven time periods within 24 h, and six blood glucose level groups to calculate the incidence of coma. A multivariate logistic regression model was constructed to analyze independent risk factors for coma in hypoglycemic patients.Results:A total of 754 patients with blood glucose levels ≤3.9 mmol/L were collected, with 425 cases of coma and 329 non-coma cases, resulting in a coma probability of 56.37% (95% CI: 52.82%-59.91%). Patients in the coma group were older ( P<0.001) and had a higher prevalence of diabetes compared to the non-coma group (82.12% vs. 67.78%, P<0.001). The age of all patients was (73.05±15.20) years, with the 61-90 years age groups being the most prone to hypoglycemia and coma. In terms of time distribution, the high-incidence periods for hypoglycemia and coma were 0-6 o’clock, 6-9 o’clock, and 14-18 o’clock. The primary causes of hypoglycemia included reduced energy intake after insulin injection (12.07%), improper use of insulin (6.37%), and reduced energy intake (6.23%), with 71.09% of cases having unknown causes. Additionally, 18.44% of patients used insulin before the onset of hypoglycemia, with a higher proportion in the coma group compared to the non-coma group (22.12% vs. 13.68%, P=0.003). The initial blood glucose level of all patients was (2.13±0.85) mmol/L, with lower levels observed in the coma group compared to the non-coma group ( P<0.001). The probabilities of coma occurrence corresponding to blood glucose levels were: 1.1-1.5 mmol/L (72.97%), 1.6-2.0 mmol/L (68.90%), 2.1-2.5 mmol/L (54.10%), 2.6-3.0 mmol/L (38.20%), 3.1-3.5 mmol/L (37.50%), and 3.6-3.9 mmol/L (19.40%). Multivariate logistic regression analysis indicated that age ( OR=1.021, 95% CI: 1.010-1.033, P<0.001), insulin use before onset ( OR=1.948, 95% CI: 1.142-3.323, P=0.014), and blood glucose concentration ( OR=0.426, 95% CI: 0.347-0.522, P<0.001) were independent predictors of coma in hypoglycemic patients. The investigation revealed that after intravenous injection of 50% glucose solution, 215 of 425 coma patients regained consciousness (50.58%), and the recovery time was (18.43±9.09) min. Patients in the recovery group were younger and had lower initial blood glucose levels compared to the non-recovery group (both P<0.05), while recovery group re-measured blood glucose levels were higher than those in the non-recovery group ( P=0.002). Conclusions:The probability of coma in hypoglycemic patients was high, with insulin use being a common trigger. Proper use of insulin is essential to prevent hypoglycemia and coma.

Objective:This study aimed to investigate temporal trends in Event survival after OHCA from 2015 to 2019 in Jiading district Shanghai. And analysis the influencing factors.Methods:This was a population based observational cohort study evaluating the temporal trends in survival after OHCA, we included consecutive patients who experienced an OHCA between January 1,2015 and December 31, 2019, we included all adult patients aged ≥ 18 years who presumed medical cause and were treated by emergency medical services (EMS) in Jiading District. The Data was obtained from Dispatch software system, The emergency case registration system, paper-based treatment records, dispatcher's telephone recording and in-hospital records, This Data organized according to the Utstein template using standard data element definitions. Temporal changes were measured by chi-square trend test. we constructed a multilevel logistic regression model to identify factors independently associated with event survival arrival at hospital and survival to hospital discharge.Results:A total of 1305 patients with OHCA met study inclusion criteria during the study period. Survival to hospital admission was 4.14% increased from 1.87% in 2015 to 7.31% in 2019 for trend ( P=0.009), survival to hospital discharge was 1.23%, increased from 0.37% in 2015 to 3.32% in 2019 ( P=0.003). But there was no evidence of a temporal change in survival to hospital discharge with good neurologic function (0.37 in 2015 to1.33% in 2019, P=0.339 for trend). In the subgroup, the rate of Recognition was increased from 7.49% in 2015 to 19.27% in 2019 ( P< 0.01). The proportion of cases receiving bystander CPR was 17.39%, which increased from 9.36% in 2015 to 25.19% in 2019 ( P= 0.000). The proportion of shockable rhythm was 4.06%, there was no evidence of a temporal change in the proportion of the overall rhythm (3.00%-4.65%, P=0.323 for trend), There were no cases of bystanders using automated external defibrillators (AEDs) in patients with cardiac arrest, The EMS response time (min) were15.45±8.71, which decreased from 15.10±8.12 in 2015 to 13.41±6.47 in 2019 ( P< 0.0001). Multiple regression analysis showed that Male ( OR= 0.315, 95% CI: 0.168-0.519, P =0.000), Not Shockable rhythm ( OR= 0.096, 95% CI: 0.043-0.012, P=0.000), and public location ( OR=2.411, 95% CI: 1.302-4.463, P=0.005) were independent predictor of Factors Associated with survival at hospital admission. Male ( OR= 0.247, 95% CI: 0.070-0.866, P=0.029), Not Shockable rhythm ( OR= 0.072, 95% CI: 0.016-0.318, P=0.001), and No Epinephrine administration ( OR=5.953, 95% CI:1.222-29.012, P=0.005) were independent predictor of Factors Associated with Survival to Hospital Discharge. Conclusions:Survival after OHCA has improved over time. Several targeted initiatives established along the chain of survival of OHCA during the past 5-years may help explain the improvement in survival outcome observed in Jiading District, including improved the rate of Recognition, improved participation rates in bystander CPR and a reduction in EMS response time.In the future, more resources should be improving the quality of CPR training and expanding AEDs coverage and encouraging the public to have the courage to use them.

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

Objective:To explore the effect of enriched environment on pain sensitivity, anxiety- and depressive-like behavior in selective nerve injury(SNI) rats model and its potential mechanism.Methods:A total of 36 male clean grade SD rats aged 6-8 weeks were randomly divided into three groups( n=12 in each group): sham operation+ standard environment group (sham group), SNI+ standard environment group (standard environment group), SNI+ enriched environment group (enriched environment group). The rat model of neuropathic pain was established by SNI.The rats in the enriched enviroment group were placed in an enriched enviroment 7 days before operation until 21 days after operation.The paw withdraw threshold(PWT) and paw withdraw latency (PWL) were performed to assess hyperalgesia.The open field test, elevated plus maze test, novelty suppressed feeding test and forced swimming test were used to assess anxiety and depression like behavior.The expressions of cAMP response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95) and neuroligin 2 (NLGN2) were detected by Western blot.The expression of CREB and BDNF in contralateral ACC were measured by immunofluorescence.GraphPad prism 8.0 and SPSS 23.0 were used for data analysis.One way ANOVA was used for inter group comparison, repeated measurement ANOVA was used to analyze PWT and PWL results, and Tukey test was used for pairwise comparison. Results:(1) In PWT and PWL experiments, the interaction effect between group and time, group main effect and time main effect of PWT were significant ( F=13.4, 39.6, 369.6, all P<0.05), and the interaction effect between group and time, group main effect and time main effect of PWL were significant ( F=3.8, 10.3, 58.8, all P<0.05). Compared with sham group, PWT((8.0±3.5) g, (2.4±1.4) g, (2.3±1.1) g, (2.2±1.6) g, (1.6±0.5) g) and PWL((8.6±1.3) s, (7.3±1.5) s, (7.9±1.0) s, (6.6±1.1) s, (7.7±1.4) s) in standard environment group decreased at each time point (all P<0.05). (2) Compared with sham group, the number of entrying into the central area (1.3±1.7), the time of entrying into the central area((1.6±1.3) s), the proportion of entering open arms ((8.0±7.8) %) and the proportion of time in the open arms ((1.3±1.2) %) all significantly decreased in standard environment group ( t=4.585, 5.423, 4.682, 5.202, all P<0.05). The eating latency ((365.2±94.4) s) and immobility time ((127.6±24.3) s) dramatically increased ( t=6.008, 14.290, both P<0.05). The number and time of entrying into central area of enriched environment group were both higher than those of standard environment group(both P<0.05), while the eating latency and immobility time of enriched environment group were both lower than those of standard environment group(both P<0.05). (3) Compared with sham group(CREB: (1.6±0.2), (0.8±0.5); BDNF: (0.8±0.5), (1.0±0.4)), the expression of CREB ((1.8±0.1), (1.5±0.2)), BDNF ((0.9±0.6), (1.4±0.3)) in spinal cord and ACC of standard environment group increased (spinal: t=3.283, 4.989; ACC: t=5.502, 4.257, all P<0.05). The expression of PSD-95 ((1.6±0.2), (1.0±0.2) and NLGN2 ((1.5±0.5), (1.1±0.2)) also increased in ACC of standard enviroment group ( t=4.257, 2.214, both P<0.05). Compared with standard environment group, the expression of CREB (1.3±0.3), BDNF (0.7±0.4), PSD-95(1.0±0.3) and NLGN2(1.1±0.4) in spinal cord of enriched environment group decreased ( t=5.007, 2.166, 2.358, 2.322, all P<0.05). The expression of PSD-95(1.2±0.3) and NLGN2(1.1±0.2) also decreased in ACC of enriched environment group ( t=2.674, 2.944, both P<0.05). However, the expression of p-CREB (1.7±0.6) and BDNF (2.4±0.2) increased in ACC ( t=4.180, 7.610, P<0.05). Conclusion:Enriched environment can improve neuropathic pain and anxiety- and depressive-like behavior in SNI rats, which may be related to the change of synaptic plasticity in spinal cord and ACC.

Objective:To assess the association between the different prehospital transfer pathways to the hospital and reperfusion delay in patients with ST segment elevation myocardial infarction (STEMI).Methods:We retrospective collected 320 STEMI patients aged 18 years or older who underwent primary percutaneous coronary intervention (PPCI) from June 1, 2016 to July 31, 2018. They were divided into three groups according to different prehospital transfer pathways: patients directly transferred from the field by ambulance to PCI-capable center hospital (field transfer group, n=29); patients transferred by ambulance from PCI-incapable hospitals to PCI-capable center hospital (inerhospital transfer group, n=111); patients transferred by friends or relatives to PCI-capable center hospital (self-transfer group, n=180). The basic characteristic attributes, reperfusion time and fatal complications such as acute left heart failure cases (ALHF) cases, ventricular fibrillation (VF) cases, and in hospital death were collected and compared. In addition, logistic regression analysis was used to analyze uni- and multivariate of door-to-balloon (D2B) time less than 90 min. Results:The S2FMC interval were 118 min (50, 377) min , FMC-to-balloon interval were 87 min (66, 120.5) min and the onset-to-balloon time were 221 min (135, 482.5) min. The above three interval in the interhospital transfer group were longer than those in the field transfer and self-transfer groups ( P<0.05). S2FMC accounted for 51.14% of onset-to-balloon time in the field transfer group, 63.29% in the interhospital transfer group and 55.26% in the self transfer group. The door-to-catheter room interval were 33 min (9, 53.5) min. The interval in the interhospital transfer group were shorter than those in the field transfer and self-transfer groups ( P<0.05). The interval in the self-transfer group were longer than those in the interhospital transfer and field transfer groups ( P<0.05). Multiple regression analysis showed that the interhospital transfer group ( OR=15.251, 95% CI: 5.328-43.657, P<0.01), field transfer group ( OR=8.219, 95% CI: 1.861-36.307, P=0.005), FMC2ECG time ( OR=0.975, 95% CI: 0.962-0.989, P<0.01), and smoking ( OR=2.099, 95% CI: 1.015-4.341, P=0.045) were independent predictor of goal time less than 90 min ( P<0.05 for all variables). Adverse events in STEMI patients mainly occurred within 6 h of the initial symptoms. The incidence of VF was 3.75% (95% CI: 3.73%-3.77%), ALHF was 10.94% (95% CI: 7.52%-14.36%) and in-hospital mortality was 2.5% (95% CI: 0.79%-4.21%). There was no significant difference in the incidence of adverse events among the three groups ( P>0.05). Conclusions:The symptoms of STEMI patients are at risk in the early stage. Ambulances can shorten the reperfusion time, but the ambulance system is less used by patients. It is necessary to further optimize the treatment process of non-PCI hospitals and strengthen the popularity of emergency knowledge related to chest pain among residents, so as to shorten the reperfusion time.

Objective:To observe the effect of Xueniaoan tablets on the expression of complement regulatory protein CR1 in IgA nephropathy rats. Methods:Totally 36 SD rats were randomized into the normal group,the model group and Xueniaoan group after 4-day adaptive feeding. Complex method was used to establish IgA nephropathy model,and Xueniaoan group was given Xueniaoan at the dose of 7.0 g·kg-1during the 10thweek and the 12thweek,while the normal group and the model group were fed with normal saline, and the administration course was 3 weeks. The 24-h urine protein was detected,CR1 in red blood cells was detected by ELISA,the renal pathological changes were observed under a light microscope after HE staining,and the expression of CR1 was detected by immu-nohistochemistry. Results:Compared with that in the model group,the 24-h proteinuria in Xueniaoan group was significantly reduced, the number of red blood cell CR1 increased significantly (P<0.05), CR1 in renal tissue increased and the renal tissue injury was light. Conclusion:Xueniaoan tablets can delay the renal damages in IgA nephropathy rats through promoting the expression of CR1.

Objective To investigate the diagnostic value of intraductal ultrasonography for the quality of biliary stricture.Methods Data of the patients who had received operation because of biliary stricture after IDUS examination from 2006 to 2010 were collected.IDUS results were compared with those of operation.Results There were 43 cases of malignant strictures and 6 benign strictures in total.The sensitivity,specificity,positive predictive value,negative predictive value and diagnostic accuracy of intraductal uhrasonography for the quality of biliary stricture were 97.7％ ( 42/43 ),83.3％ ( 5/6 ),97.7％ ( 42/43 ),83.3％ (5/6) and 95.9％ (47/49),respectively,which were significantly higher than conventional imaging like ultrasound B,CT and MRCP.Twenty one cases in 32 were diagnosed as malignant biliary stricture with cytological brushing,with the diagnostic accuracy of 65.6％.All cases had been diagnosed by IDUS.Conclusion Intraductal ultrasonography is of high diagnostic value for biliary stricture.However,cytological brushing based on IDUS is of limited diagnostic value for malignant biliary stricture.