ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

Objective To explore the effect of intermittent fasting combined with diversified management mode on weight loss of overweight and obese people. Methods A total of 120 overweight and obese patients were selected as research objects, and randomly divided into control group (n=60) and experimental group (n=60). The control group was given intermittent fasting, and the experimental group was given diversified management mode on the basis of the control group. Waist circumference, body mass, body mass index (BMI), waist-to-hip ratio and blood lipid level were compared between the two groups; the scores of hunger, satiety, satisfaction and the incidence of adverse reactions were compared between the two groups. Results After intervention, waist circumference, body mass, BMI, waist-to-hip ratio, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the experimental group were significantly lower, and high-density lipoprotein cholesterol (HDL-C) was significantly higher than that in the control group (P < 0.05). After intervention, the hunger score of the experimental group was significantly lower, and the satiety score and satisfaction score were significantly higher than those of the control group (P < 0.05). The total incidence of adverse reactions in the experimental group was 6.67%, which was significantly lower than 20.00% in the control group (P < 0.05). Conclusion The application of intermittent fasting combined with diversified management mode in overweight and obese people is better, which can improve the relevant clinical indicators and blood lipid levels, and has high safety.

Objective:To investigate the expression of Toll-like receptor 4(TLR4)and extracellular signal-regulated protein kinase 1/2(ERK1/2)in decidua tissue of patients with unexplained spontaneous abortion and their correlation.Methods:The expres-sions of TLR4,ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion(abortion group)and 32 normal pregnancy(control group)were detected by immunohistochemistry and Western blot,respectively.The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis.Results:In immunohistochemical experiments,the cytoplasm of decidua cells in the two groups is the expression locus of TLR4,ERK1/2 and p-ERK1/2,the expression of the three proteins were different,and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group(P<0.01).There was no significant difference in ERK1/2 expression between abortion group and control group(P>0.05);In decidua tissue samples of abortion group,the protein level of TLR4 was higher than that of control group(P<0.05);the pro-tein level of p-ERK1/2 was significantly higher than that of control group(P<0.01),and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group(P>0.05).TLR4 was positively correlated with p-ERK1/2 expression in abortion group(r=0.890,P<0.01).Conclusion:Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion.

Passing the hospital grading evaluation, establishing a tertiary-A specialized hospital for occupational diseases, enhancing hospital's internal quality and sustainable development, and continuously improving medical service quality are important measures to promote the high-quality development of hospitals. The evaluation standards for occupational disease specialized tertiary-A hospital require standardized, scientific, and sustainable management of medical equipment. Guangdong Province Hospital for Occupational Disease Prevention and Treatment is the first tertiary-A hospital for occupational diseases specialized in Guangdong Province. Relative regulation on medical equipment management was systematically reviewed based on the requirement of tertiary-A specialized hospital for occupational diseases during hospital grading evaluation process. Building and completing the medical equipment management system, standardizing and strengthening government procurement management, completing the configuration management and safety management of large-scale medical equipment, strengthening the effectiveness analysis and evaluation of large equipment, enhancing training on medical equipment usage, establishing emergency allocation systems for first-aid and life support medical equipment, and forming a medical equipment quality and safety management team is the measure to systematically improve and implement each item in various regulation for the full lifecycle management of medical equipment. It provides vital support in passing the tertiary-A hospital evaluation for hospitals. During the hospital grading evaluation process, each issue identified in medical equipment management was addressed and improved. This process continuously enhanced the hospital's medical equipment management level, ensured the safe and effective use of medical equipment, and improved the quality of medical services, laying a solid foundation for the hospital to become a high level specialized medical institution for occupational diseases.

ObjectiveTo study the sexually transmitted infections （STIs） in pregnant women with non-local household registration in Xuhui District and analyze the risk factors for STIs. MethodsFrom April 2020 to March 2022， pregnant women with non-local household registration who received their first prenatal examination in a general hospital in Shanghai Xuhui District were selected to conduct a status survey of STIs. Logistic regression model was used to analyze the influencing factors of bacterial vaginitis and ureaplasma uaplasma infection. ResultsThe top three infection rates in the pregnant women were Ureaplasma urealyticum （13.2%）， bacterial vaginosis （9.8%） and mycotic vaginitis （4.7%）. Age between 25 and 35 years （aOR=0.53，95%CI： 0.28‒0.98） and monthly income ≥8 000 yuan （aOR=0.30，95%CI： 0.11‒0.82） were significantly correlated with ureaplasma uaplasma infection. Pregnancy number of 2 （aOR=4.95， 95%CI： 1.59‒15.46）， first sexual relationship occurred before marriage （aOR=2.83， 95%CI： 1.04‒7.74）， husband's alcoholism （aOR=3.83， 95%CI： 1.08‒13.56）， high school education （aOR=0.27， 95%CI： 0.08‒0.93）， and husband's travel history （aOR=0.30， 95%CI： 0.12‒0.79） were significantly correlated with bacterial vaginitis. ConclusionPregnant women with more gestation times， first sexual intercourse before marriage and husband with heavy drinking are more likely to be infected with bacterial vaginosis. Pregnant women with younger age and lower income are more likely to be infected with Ureaplasma urealyticum. Follow-up and monitoring should be strengthened in these groups.

Objective:To explore the risk factors and the predicting value of early urinary tract infection in patients treated with tacrolimus (TAC)-containing immunosuppressive regimen after kidney transplantation.Methods:The medical records of patients who underwent allogeneic kidney transplantation in the Provincial Hospital Affiliated to Shandong First Medical University from January 1, 2015 to October 30, 2021 and received triple immunosuppressive regimen with TAC+mycophenolate mofetil+methylprednisolone were collected and analyzed retrospectively. Relevant clinical data of patients were extracted from the hospital information system. Patients were divided into infection group and non-infection group according to whether urinary tract infection occurred within 1 month after taking TAC and the clinical characteristics in patients between the 2 groups were compared. The risk factors of urinary tract infection were analyzed by binary logistic regression method, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of risk factors on the risk of urinary tract infection. Results:A total of 256 patients were entered in the analysis, including 208 males and 48 females, aged 34 (29, 42) years with an range from 18 to 66 years, and the body mass index of these patients was 22.9 (20.4, 25.4) kg/m 2, ranging from 13.9 to 34.4 kg/m 2. There were 163 living donors from relatives and 93 cardiac dead organ donors (DCD). Among the 256 patients, 56 had urinary tract infection (asymptomatic bacteriuria in 32 patients and symptomatic urinary tract infection in 24 patients) after kidney transplantation with an incidence of 21.9%. The differences in gender, age, body weight, body mass index, primary disease, comorbidity disease, donor source, length of hospital stay after surgery, time of indwelling urinary tube and ureteral stent, postoperative complications, complicated infection in other parts of the body after surgery, laboratory test results and so on in patients between the 2 groups were not significant (all P>0.05). The trough plasma concentrations of TAC on the 7th, 14th, and 21st days after taking TAC in the infection group was higher than those in the non-infection group [9.7 (8.4, 13.5) μg/L vs. 8.0 (6.3, 9.8) μg/L, P<0.001; 9.4 (7.6, 11.0) μg/L vs. 8.0 (6.3, 9.8) μg/L, P=0.002; 9.2 (7.6, 11.1) μg/L vs. 8.2 (6.3, 9.8) μg/L, P=0.002]. The binary logistic regression analysis showed that the high trough plasma concentrations of TAC on the 7th day after taking TAC ( OR=1.815, 95 %CI: 1.332-2.474, P<0.001) was an independent risk factor for urinary tract infection in the early stage after kidney transplantation. The ROC curve analysis results showed that the area under the ROC curve of TAC trough plasma concentration on the 7th day was 0.704 (95 %CI: 0.626-0.782), with the cutoff value 8.35 μg/L, the sensitivity 76.8%, and the specificity 53.5%. The patients were divided into >8.35 μg/L group and ≤8.35 μg/L group according to this cutoff value, the incidences of urinary tract infection in the 2 groups were 31.4% (43/137) and 20.6% (13/119) respectively and the difference was statistically significant ( χ2=15.603, P<0.001). Conclusion:High trough plasma concentration of TAC on the 7th day after taking TAC is an independent risk factor for urinary tract infection after kidney transplantation and the predicting value is 8.35 μg/L, which has certain predicting value for early urinary tract infection after kidney transplantation.

Objective:To explore the risk factors and the predicting value of early urinary tract infection in patients treated with tacrolimus (TAC)-containing immunosuppressive regimen after kidney transplantation.Methods:The medical records of patients who underwent allogeneic kidney transplantation in the Provincial Hospital Affiliated to Shandong First Medical University from January 1, 2015 to October 30, 2021 and received triple immunosuppressive regimen with TAC+mycophenolate mofetil+methylprednisolone were collected and analyzed retrospectively. Relevant clinical data of patients were extracted from the hospital information system. Patients were divided into infection group and non-infection group according to whether urinary tract infection occurred within 1 month after taking TAC and the clinical characteristics in patients between the 2 groups were compared. The risk factors of urinary tract infection were analyzed by binary logistic regression method, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of risk factors on the risk of urinary tract infection. Results:A total of 256 patients were entered in the analysis, including 208 males and 48 females, aged 34 (29, 42) years with an range from 18 to 66 years, and the body mass index of these patients was 22.9 (20.4, 25.4) kg/m 2, ranging from 13.9 to 34.4 kg/m 2. There were 163 living donors from relatives and 93 cardiac dead organ donors (DCD). Among the 256 patients, 56 had urinary tract infection (asymptomatic bacteriuria in 32 patients and symptomatic urinary tract infection in 24 patients) after kidney transplantation with an incidence of 21.9%. The differences in gender, age, body weight, body mass index, primary disease, comorbidity disease, donor source, length of hospital stay after surgery, time of indwelling urinary tube and ureteral stent, postoperative complications, complicated infection in other parts of the body after surgery, laboratory test results and so on in patients between the 2 groups were not significant (all P>0.05). The trough plasma concentrations of TAC on the 7th, 14th, and 21st days after taking TAC in the infection group was higher than those in the non-infection group [9.7 (8.4, 13.5) μg/L vs. 8.0 (6.3, 9.8) μg/L, P<0.001; 9.4 (7.6, 11.0) μg/L vs. 8.0 (6.3, 9.8) μg/L, P=0.002; 9.2 (7.6, 11.1) μg/L vs. 8.2 (6.3, 9.8) μg/L, P=0.002]. The binary logistic regression analysis showed that the high trough plasma concentrations of TAC on the 7th day after taking TAC ( OR=1.815, 95 %CI: 1.332-2.474, P<0.001) was an independent risk factor for urinary tract infection in the early stage after kidney transplantation. The ROC curve analysis results showed that the area under the ROC curve of TAC trough plasma concentration on the 7th day was 0.704 (95 %CI: 0.626-0.782), with the cutoff value 8.35 μg/L, the sensitivity 76.8%, and the specificity 53.5%. The patients were divided into >8.35 μg/L group and ≤8.35 μg/L group according to this cutoff value, the incidences of urinary tract infection in the 2 groups were 31.4% (43/137) and 20.6% (13/119) respectively and the difference was statistically significant ( χ2=15.603, P<0.001). Conclusion:High trough plasma concentration of TAC on the 7th day after taking TAC is an independent risk factor for urinary tract infection after kidney transplantation and the predicting value is 8.35 μg/L, which has certain predicting value for early urinary tract infection after kidney transplantation.