ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.

Objective To investigate the effect of microglial derived extracellular vesicles on neuronal damage in the context of heat stress.Methods After BV2 microglial cells were exposed to heat stress,the supernatant was collected and subjected to ultracentrifugation at different speeds to obtain large and small vesicles,respectively.Nano Particle Tracking and Zeta Potential Distribution Analyzer was used to measure and analyze the size distribution of the large vesicles and small vesicles.Western blotting was used to detect the expression of specific vesicle surface markers,TSG101,CD63 and flotillin-1.Microglial extracellular vesicles were labeled with PKH67 dye and then co-cultured with N2a cells to examine the uptake by capacity the neurons.After large and small vesicles derived from microglia after heat stress stimulation were co-cultured with N2a cells,respectively,CCK-8 assay,lactate dehydrogenase (LDH)assay,Trypan blue staining and TUNEL assay were employed to evaluate heat stress induced neuronal damage.Results The small vesicles were in a particle size of 30～120 nm,and highly expressed TSG101 and CD63,whereas the large vesicles,in a size of 90～1000 nm,highly expressed flotillin-1.The BV2-derived extracellular vesicles could be taken up by N2a cells and were proved to be involved in the modulation of N2a cell injury caused by heat stress.CCK-8 assay showed that both large and small vesicles of microglial cells inhibited the viability of N2a cells after heat exposure (P<0.05).The results of LDH assay,Trypan blue staining and TUNEL assay showed that both large (P<0.05)and small vesicles (P<0.01)significantly enhanced the LDH release,blue stain intensity and apoptosis of N2a cells after heat exposure,and the release,intensity and apoptosis were stronger in the cells treated with small vesicles than those group of large vesicles.Conclusion Microglia aggravate heat stress-induced neuronal damage through releasing extracellular vesicles.

Objective:This study investigates the influence of the apolipoprotein E ε4(APOE ε4)genotype on the relationship between glucose-lipid metabolism disorders and diabetes-related cognitive impairment(DCI).Methods:A case-control study was conducted involving 891 patients with type 2 diabetes mellitus(T2DM)with a mean age of(62.1±13.8)years, all of whom underwent elective surgery at the First Hospital of Shanxi Medical University between January 2017 and December 2022.Among these participants, 229 were diagnosed with DCI(case group), while 662 were cognitively normal(control group).Routine clinical information was collected, and peripheral venous blood samples were analyzed for glycated hemoglobin(HbA1c)and blood lipid levels.The single nucleotide polymorphisms rs429358 and rs7412 were analyzed to determine the presence of the APOE ε4 genotype.Stepwise Logistic regression was employed to identify independent risk factors for DCI, and subgroup analyses were performed to evaluate the effect of the APOE ε4 genotype on the relationship between HbA1c and blood lipid levels in relation to DCI risk. Results:Among all patients, female gender( OR=1.915, 95% CI: 1.393-2.631, P<0.001), longer duration of T2DM( OR=1.169, 95% CI: 1.087-1.257, P<0.001), elevated triglycerides( OR=1.161, 95% CI: 1.041-1.294, P=0.007), and being an APOE ε4 carrier( OR=1.638, 95% CI: 1.115-2.405, P=0.012)were identified as independent risk factors for developing DCI.High levels of low-density lipoprotein(LDL)were found to be independently associated with an increased risk of DCI specifically in APOE ε4 carriers( OR=1.408, 95% CI: 1.060-1.870, P=0.018), but not in non-APOE ε4 carriers( P>0.05).In contrast, elevated HbA1c was independently associated with a higher risk of DCI in non-APOE ε4 carriers( OR=1.220, 95% CI: 1.040-1.430, P=0.014), but not in APOE ε4 carriers( P>0.05).Additionally, elevated triglycerides were independently linked to an increased risk of DCI across the entire sample and within each APOE ε4 genotype subgroup. Conclusions:The APOE genotype plays a significant role in modulating the relationship between dyslipidemia and the risk of developing DCI.This highlights the critical importance of lipid metabolism disorders and APOE risk genes in both the development and progression of DCI.These findings offer valuable insights for future clinical and mechanistic studies focused on DCI.

Objective: To explore the effects of melatonin(MT) on the fertilization of in vitro matured oocytes in controlled ovarian hyperstimulation(COH) cycles and the development of subsequent embryos. Methods: Imma-ture human oocytes from COH cycles were collected for in vitro maturation(IVM) culture and intracytoplasmic sperm injection( ICSI) insemination,and then the cleavage embryo and blastocyst culture medium supplemented with 0,10-11,10-9,10-7or 10-5mol/L MT were used in order to perform embryo culture in vitro,next the formed high-quality blastocysts were picked up and cryopreserved via vitrification,finally,array-CGH technology was used to detect aneuploidy of rewarmed high-quality blastocysts. Results: The blastocyst rate of 10-9mol/L group was significantly higher than that of 10-11,10-7,10-5and 0 mol/L groups( P<0. 05,P<0. 01,P<0. 000 1,P<0. 01),respectively; the high-quality blastocyst rate of 10-9mol/L group was higher than that of other groups,but there were only significant differences compared with 10-5mol/L and 0 mol/L groups( P<0. 01,P<0. 05); the incidence of aneuploidy in MT group( 17. 6%) was lower than that in non-MT group( 33. 3%),but no significant difference was found. Conclusion The addition of MT to human embryo culture medium can promote the in vitro development of embryo,which is related to concentration,and 10-9mol/L is the optimal concentration.

Objective:To evaluate the effect of driving pressure-guided individualized positive end-expiratory pressure (PEEP) titration on atelectasis in elderly patients undergoing robot-assisted radical prostatectomy.Methods:Fifty elderly patients, aged 65-80 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 19-28 kg/m 2, undergoing elective robot-assisted radical prostatectomy under general anesthesia, were divided into 2 groups ( n=25 each) according to the random number table method: traditional lung-protective ventilation group (group C) and driving pressure-guided individualized PEEP group (group D). The method for setting PEEP was as follows: PEEP 5 cmH 2O was used throughout operation in group C. In group D, the optimal PEEP was titrated after intubation and mechanical ventilation and Trendelenburg position-pneumoperitoneum construction, the initial value was the lowest PEEP allowed by the anesthesia machine, the PEEP was increased by 1 cmH 2O (PEEP≤12 cmH 2O) every 4 min, the plateau pressure and PEEP were simultaneously recorded to calculate the driving pressure, and the corresponding PEEP was considered as the optimal PEEP for the individual when the driving pressure reached the minimum.Ultrasound examination was performed after catheterization of radial artery (T 0), after anesthesia induction (T 1), 4 min after developing optimal PEEP ventilation (T 2, 4 min after developing ventilation in group C), after restoration of body position (T 3), before extubation (T 4), and at 2 h after admission to postanesthesia care unit (T 5). Atelectatic aeration loss scores were recorded at T 0, T 1, T 4 and T 5.Bilateral optic nerve sheath diameter was measured at T 0-4.Arterial blood gas analysis was performed at T 0, T 2, T 3 and T 5, PaO 2 and PaCO 2 were recorded, and oxygenation index was calculated.The postoperative pulmonary complications within 3 days after operation were recorded. Results:Compared with group C, atelectasis aeration loss scores at T 4, 5 and PaCO 2 at T 2, 3 were significantly decreased, and PaO 2 and oxygenation index were increased at T 2, 3, 5 in group D ( P<0.05). There were no significant differences in the bilateral optic nerve sheath diameter and incidence of postoperative pulmonary complications between the two groups ( P>0.05). Conclusion:Driving pressure-guided individualized PEEP can increase intraoperative oxygenation and decrease the development of atelectasis in elderly patients undergoing robot-assisted radical prostatectomy.

Objective To evaluate the effect of dynamic lung compliance ( Cydn)-guided positive end-expiratory pressure (PEEP) titration on lung injury in the patients undergoing robot-assisted radical prostatectomy. Methods Forty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-80 yr, with body mass index of 19-28 kg∕m2 , scheduled for elective robot-assisted radical prosta-tectomy under general anesthesia, were divided into 2 groups ( n=20 each) using a random number table method: control group (group C) and PEEP group (group P). Mechanical ventilation was performed ac-cording to preset parameters after tracheal intubation in group C, and PEEP was set by a double titration method after tracheal intubation and after pneumoperitoneum in group P. At 4 min after intubation (T1), 4 min, 1 h and 2 h after establishing pneumoperitoneum-Trendelenburg position ( T2-4 ) , and 1 and 30 min after extubation ( T5,6 ) in group C or at 4 min after completing the first PEEP titration ( T1 ) , 4 min, 1 h and 2 h after completing the second PEEP titration (T2-4) and T5,6 in group P, blood samples were collect-ed from the radial artery for determination of club cell protein 16, surfactant protein-D, tumor necrosis fac-tor-alpha and interleukin-6 concentrations in serum ( by enzyme-linked immunosorbent assay) . Results Compared with group C, the serum concentrations of club cell protein 16 at T2-6 and surfactant protein-D, tumor necrosis factor-alpha and interleukin-6 at T3-6 were significantly decreased in group P (P<0. 05). Conclusion Cydn-guided PEEP titration can reduce the lung injury in patients undergoing robot-assisted radical prostatectomy.

Objective To evaluate the effect of dynamic lung compliance ( Cdyn) -guided positive end-expiratory pressure (PEEP) titration on extravascular lung water in elderly patients undergoing robot-assisted radical prostatectomy. Methods Forty American Society of Anesthesiologists physical statusⅡ orⅢ patients, aged 65-80 yr, with body mass index of 19-28 kg∕m2 , scheduled for elective robot-assisted radical prostatectomy, were divided into 2 groups ( n=20 each) using a random number table method:control group (group C) and PEEP group (group P). In group P, immediately after endotracheal intuba-tion, immediately after establishing pneumoperitoneum-Trendelenburg position and after restoring the supine position, PEEP was set starting from the lowest PEEP allowed by the machine, increasing by 2 cmH2 O ev-ery 4 min until the maximum Cdyn was obtained. PEEP was not set in group C. Immediately after establis-hing the invasive blood pressure monitoring ( T1 ) , at 10 min after the first successful PEEP titration ( T2 ) , 10 min, 1 h and 2 h after the second successful PEEP titration ( T3-5 ) , 10 min after the third successful PEEP titration (T6), and 30 min after tracheal extubation (T7) in group P, or at T1, 10 min after intu-bation ( T2 ) , 10 min, 1 h and 2 h after establishing pneumoperitoneum-Trendelenburg position ( T3-5 ) , 10 min after restoring the supine position ( T6 ) and T7 in group C, blood samples were collected from the radial artery for blood gas analysis, and the oxygenation index was calculated. The B-line score was recor-ded at T1 and T7 . Results Compared with group C, the B-line score was significantly decreased at T7 , and the oxygenation index was increased at T5-7 in group P (P<0. 05). Conclusion Cdyn-guided PEEP titration can decrease the formation of extravascular lung water in elderly patients undergoing robot-assisted radical prostatectomy.

Objective To clarify the age patterns and types of differences so as to provide reference on prevention and interventions of hand,foot and mouth disease (HFMD) cases,in Hubei province.Methods We collected the HFMD case information of Hubei province from the Chinese National Notifiable Infectious Disease Reporting System in 2009-2015 while the information on pathogens from the laboratory monitoring system of Center for Disease Control and Prevention at all levels in Hubei province.All the data were stratified by age,disease severity,laboratory confirmation status,and serotypes of enterovirus.Results There were 495 783 reported HFMD cases from 2009 to 2015,in Hubei province,of which 1 045 were severe with 99 fatal.The annual notification rate was 1 231.0/106.HFMD cases were concentrated mainly in 0.5-5 year olds,with highest severity and mortality seen in 6-11 month-olds.The predominated pathogen in mild laboratory-confirmed cases each year,in order during 2009-2015 as:EV71,Cox A16,Cox A16,Cox A16,EV71,Cox A16 and other EV.HFMD showed semiannual peaks in April-June,November-December,and with more cases in the even years than in the odd years.Conclusions Children aged 0.5 to 5 years with 6 to 11 month-olds in particular,were the focused groups of attention in Hubei province.Our findings provided evidence for the improvement on monitoring program.Targeted intervention approaches should be strengthened to reduce the mortality and morbidity of HFMD in the province.