Objective To develop an ultra high performance liquid chromatography-mass spectrometry(UPLC-MS)method for quantifying serum levels of norepinephrine(NE)and 5-hydroxytryptamine(5-HT),and to monitor the dynamic changes in these neurotransmitters during the process of establishing a model of acute reserpine-induced depression-like mice.Methods By evaluating matrix effect,recovery,precision,and accuracy efficiency,an UPLC-MS method for determining the concentrations of NE and 5-HT in serum was established.Forty-eight C57 mice were randomly divided into normal control and model groups,which were intraperitoneally injected with physiological saline(10 mL/kg)and reserpine(2.5 mg/kg),respectively.At various time points after intraperitoneal injection,the degree of ptosis and decreases in body temperature of the mice were observed before orbital blood was sample for the determination of NE and 5-HT levels.Results The concentrations of NE and 5-HT showed good linearity within the range of 15.63 to 2000.00 ng/mL,with R2 values greater than 0.999.The results of methodological validation met the requirements for the analysis of biological samples,with a lower limit of quantification of 15.63 ng/mg.After intraperitoneal injection of reserpine,the model mice exhibited varying body temperature decreases and ptosis.At 1 and 2 h post-administration,the depression-like symptoms in the model group were significantly different from those of the normal control group(P＜0.01).The body temperature of mice in the model group was significantly lower than that of mice in the normal control group(P＜0.01),while the score of the eyelid ptosis was significantly higher(P＜0.001).The levels of NE and 5-HT in the serum of model mice were also significantly depleted,and were significantly different from those of the normal control group at 0.5,1 and 2 h(P＜0.05).Conclusion The study process of established a rapid and accurate method for dynamically observing the changes in NE and 5-HT levels during the process of establishing a model of acute reserpine-induced depression-like mice,which might contribute to the study of the pathogenesis of depression and the development of new antidepressant drugs.

Objective To investigate the rehabilitative effects of pelvic floor muscle training(PFMT)combined with electromyography biofeedback(EMG-BF)in patients with post-prostatectomy incontinence(PPI),aims to provide refer-ence for clinical nursing practice.Methods 98 patients with PPI who were treated at the urinary incontinence nurse-led clinic of a tertiary hospital in Shanghai were included using the method of convenience sampling.Patients enrolled from June to September 2022 were assigned to a control group(n=49),receiving PFMT alone at home.Those enrolled from November 2022 to February 2023 were assigned to an experimental group(n=49),receiving PFMT at home combined with EMG-BF at the nurse-led clinic.Both groups received intervention for 3 months,preceded by guidance for PFMT provided by incontinence specialist nurses.The urine leakage in 24-hour pad test,the International Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF),the Incontinence Quality of Life Questionnaires(I-QOL),and the Broome Pelvic Muscle Self-Efficacy Scale(BPMSES)were used to assess objective and subjective incontinence severity,quality of life,and self-efficacy of PFMT on the day of catheter removal and at 1,2,and 3 months post-intervention.Results A total of 46 patients were included in each group.The 24-hour urine leakage volume and I-QOL scores demonstrated significant between-group and over-time effects(P＜0.05),with no interaction effect between groups and time(P＞0.05)The ICIQ-SF and BPMSES scores exhibited interactive ef-fects between time and groups(P＜0.05).At 2 and 3 months post-intervention,the intervention group showed signifi-cantly lower ICIQ-SF scores(P＜0.001),and higher BPMSES scores(P＜0.05),compared to those in the control group.Conclusion PFMT combined with EMG-BF can effectively alleviate the objective and subjective severity of PPI,enhance patients'self-efficacy in PFMT,and improve their postoperative quality of life.

Objective To investigate the rehabilitative effects of pelvic floor muscle training(PFMT)combined with electromyography biofeedback(EMG-BF)in patients with post-prostatectomy incontinence(PPI),aims to provide refer-ence for clinical nursing practice.Methods 98 patients with PPI who were treated at the urinary incontinence nurse-led clinic of a tertiary hospital in Shanghai were included using the method of convenience sampling.Patients enrolled from June to September 2022 were assigned to a control group(n=49),receiving PFMT alone at home.Those enrolled from November 2022 to February 2023 were assigned to an experimental group(n=49),receiving PFMT at home combined with EMG-BF at the nurse-led clinic.Both groups received intervention for 3 months,preceded by guidance for PFMT provided by incontinence specialist nurses.The urine leakage in 24-hour pad test,the International Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF),the Incontinence Quality of Life Questionnaires(I-QOL),and the Broome Pelvic Muscle Self-Efficacy Scale(BPMSES)were used to assess objective and subjective incontinence severity,quality of life,and self-efficacy of PFMT on the day of catheter removal and at 1,2,and 3 months post-intervention.Results A total of 46 patients were included in each group.The 24-hour urine leakage volume and I-QOL scores demonstrated significant between-group and over-time effects(P＜0.05),with no interaction effect between groups and time(P＞0.05)The ICIQ-SF and BPMSES scores exhibited interactive ef-fects between time and groups(P＜0.05).At 2 and 3 months post-intervention,the intervention group showed signifi-cantly lower ICIQ-SF scores(P＜0.001),and higher BPMSES scores(P＜0.05),compared to those in the control group.Conclusion PFMT combined with EMG-BF can effectively alleviate the objective and subjective severity of PPI,enhance patients'self-efficacy in PFMT,and improve their postoperative quality of life.

Objective To investigate the improvement effect and mechanism of Modified Kongsheng Zhenzhong Dan medicated serum on mitochondrial function of PC12 cells injured by oxygen-glucose deprivation/reperfusion(OGD/R)based on the SIRT1/PGC-1α pathway.Methods PC12 cells were used to construct OGD/R cell model in vitro.Cell grouping:normal group(10%FBS),model group(10%FBS),10%drug-containing serum group,5%drug-containing serum group(5%drug-containing serum+5%blank serum),10%blank serum group(control group).CCK-8 method was used to detect the cell survival rate,and the appropriate oxygen glucose deprivation time(2,4,6,8 hours)was screened.MTT assay was used to detect cell activity;mitochondrial stress test(MST)was used to detect the oxygen consumption rate(OCR).Apoptosis was detected by flow cytometry(Annexin V-PE/7-AAD double staining).The protein expression levels of SIRT1 and PGC-1α in PC12 cells were detected by Western Blot.Results Compared with the normal group,the activity of PC12 cells decreased significantly after oxygen-glucose deprivation for 2,4,6 and 8 hours(P＜0.05),and 6 hours of oxygen-glucose deprivation was selected as the time of subsequent experimental modeling.Compared with the normal group,the cell activity of the model group was significantly decreased(P＜0.05).The OCR values of basic respiration value,maximum respiration value,proton leakage,ATP production and standby respiration ability were significantly decreased(P＜0.05).The apoptosis rate was significantly increased(P＜0.05).The protein expression levels of SIRT1 and PGC-1α in cells were significantly decreased(P＜0.05).Compared with the model group,the cell activity of the Modified Kongsheng Zhenzhong Dan 10%and 5%drug-containing serum groups was significantly increased(P＜0.05).The OCR values of basal respiration value,maximum respiration value,proton leakage,ATP production and spare breathing ability were significantly increased(P＜0.05).The apoptosis rate was significantly decreased(P＜0.05).The protein expression levels of SIRT1 and PGC-1α in cells were significantly increased(P＜0.05).Conclusion The Modified Kongsheng Zhenzhong Dan medicated serum can improve mitochondrial dysfunction,inhibit neuronal apoptosis and promote neuronal survival in OGD/R-injured PC12 cells.The mechanism may be related to the activation of SIRT1/PGC-1α signaling pathway.

ObjectiveTo observe the influence of Bupi Yishen decoction on the curative effect of diabetic kidney disease rats and the tubuloglomerular feedback. MethodAmong the 100 SD male rats， 25 were randomly selected as the normal group， and the remaining 75 were treated with high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin （STZ） to establish diabetic rat model. The model rats were randomly divided into model group， Bupi Yishen group and losartan group. Bupi Yishen group and Losartan group were given Bupi Yishen decoction （23.4 g·kg^-1） and losartan tablet （9 mg·kg^-1）， respectively by gavage， and normal group and model group received equal volume of distilled water via intragastric administration. The treatment lasted for 11 consecutive weeks. Random blood glucose was measured once every two weeks. Rats in each group were put into metabolic cage and 24-hour urine volume was recorded. At the end of week 11， the rats were sacrificed for index detection. Enzyme linked immunosorbent assay （ELISA） was used to determine the quantification of 24-hour urinary microalbumin excretion rate （24 h UAER）， renal tubular injury-related proteins and urine creatinine. Blood was collected for creatinine and urea nitrogen detection. Hematoxylin-eosin （HE） staining， periodic acid-schiff （PAS） staining and Masson staining were performed to observe the pathological changes of the kidney of rats. The expression of sodium-glucose cotransporter 1 （SGLT1）， sodium-glucose cotransporter 2 （SGLT2）， sodium-potassium-chloride cotransporter 2 （NKCC2） and connexin 40 （CX40） was detected by immunohistochemistry. The location of adenosine type Ⅰ receptor （A1AR） in kidney was observed by immunofluorescence. In addition， the expression of SGLT1， SGLT2， NKCC2， CX40 and A1AR in renal tissues was determined by Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， renal pathology in model group showed increased glomerular volume， thickened basement membrane， and shed renal tubule epithelial cells. Compared with the model group， the renal pathology of bupiyishen group was improved. Compared with normal group， random blood glucose at different time points， 24 h UAER and renal tubule-injury-related proteins were increased in model group （P<0.01）， and the expressions of SGLT1 and SGLT2 in renal tissue were increased （P<0.01）， and the expression of NKCC2， CX40 and A1AR decreased （P<0.01）. Compared with the model group， the random blood glucose， 24 h UAER and renal tubular injury-related proteins in Bupi Yishen group decreased （P<0.01）， the expressions of SGLT1 and SGLT2 were down-regulated， and the expressions of NKCC2， CX40 and A1AR were increased （P<0.05）. ConclusionBupi Yishen decoction can improve glomerular and renal tubular injury and alleviate early hyperfiltration in diabetic kidney disease rats. The intervention effect of Bupi Yishen decoction on diabetic kidney disease is related to the regulation of tubuloglomerular feedback.

Objective:To explore the expression level of interleukin-1 receptor-associated kinase-1 (IRAK1) in the peripheral blood of rheumatoid arthritis (RA) patients and analyze its relevance between disease activity and CD4 + T cell subsets. Methods:① The concentration of IRAK1 in the peripheral blood of 77 RA patients and 24 healthy controls were detected by enzyme linked immunosorbent assay (ELISA). ② The demo-graphic and clinical data of the RA group including disease activity score with 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CD4 + T cell subsets in peripheral blood. ③Independent sample t test or Mann-Whitney U test were used to compare the differences between the two groups. Spearman rank correlation test and multiple linear regression were used to analyze the correlation between IRAK1 expression level and clinical data. Results:① The IRAK1 level of the peripheral blood of RA patients was significantly higher than in the normal controls ( P<0.001). ② Compared to normal controls, the peripheral blood of the RA group, the absolute numbers and proportion of regulatory T (Treg) cells were decreased ( P<0.001), the absolute numbers and proportion of helper T (Th) 17 and the ratio of Th17/Treg were increased. Moreover, the ratio of Th17/Treg was also increased. ③ With the increase of disease activity in RA patients, the expression of IRAK1 also increased. The expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR, number of joints involved and DAS28, and had statistically significant difference between the two groups ( r=0.23, P<0.05; r=0.24, P<0.05; r=0.27, P<0.05). Meanwhile, it was sign-ificantly negatively correlated with the percentage of Treg ( r=-0.27, P<0.05), and was significantly positively correlated with the ratio of Th17/Treg ( r=0.23, P<0.05) . However, there was no significant correlation with the ratio of Th1/Th2( P>0.05). Furthermore, multiple stepwise regression analysis showed that the expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR and the number of joints involved ( β=0.34, P=0.019; β=0.27, P=0.004), and it was inversely correlated with percentage of Treg ( β=-0.23, P=0.047, R2=0.219). Conclusion:IRAK1 expression in the peripheral blood of RA patients is up-regulated and correlated with disease activity. The decrease of Treg and the imbalance of Th17/Treg caused by high expression of IRAK1 may be one of the main factors for the occurrence and development of RA. Interfering the expression of IRAK1 may be a potential new target for RA treatment.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective:To investigate the value of sedation in colonoscopy.Methods:A retrospective cohort study of colonoscopy procedures was performed in our institution. Inclusion criteria: (1) colonoscopy procedures were performed by well-trained gastrointestinal surgeons our institution; (2) medical records were complete and colonoscopy was documented properly by notes, videos, photographs, and traceable pathological reports. Those with incomplete records or performed in other institution were excluded. According to above criteria, clinical data of 49 057 cases of clinic and hospitalization receiving diagnostic or therapeutic colonoscopyat Department of Gastric and Colorectal Surgery, Daping Hospital from July 2007 to February 2017 were collected. Among them, there were 24 638 (50.2%) males and 24 419 females, with mean age of (50.6±14.1) (4 to 98) years. Based on the application of sedation during colonoscopy, patients were divided into the sedation group (39 412 cases, 80.3%) and the non-sedation group (9 645 cases, 19.7%). Clinical characteristics of two groups were compared.Results:The sedation rate increased from 45.6% (369/810) to 94.8% (917/967) from 2007 to 2017. As compared to non-sedation group, a higher proportion of females [51.0% (20 095/39 412) vs. 44.8% (4 324/9 645), χ 2=117.422, P<0.001] and younger median age (50.0 years vs. 51.0 years, Z=-4.774, P<0.001) were found in the sedation group, whose differences were statistically significant. In all the 9645 cases in the non-sedation group, about 5.5% (534) of them terminated the examination because of unbearable discomfort, including 244 (4.6%) males and 290 (6.7%) females (χ 2=20.522, P<0.001). Among all the screening population who were ≥50 years old, there was no significant difference in the polyp detection rate (PDR) between the sedation group and the non-sedation group [26.7% (4 737/17 753) vs. 27.4% (1 093/3 984), χ 2=0.937, P=0.330]. The cecal intubation rate (CIR) in the sedation group was significantly higher than that in the non-sedation group [(85.2% (14 422/16 933) vs. 76.1% (2 803/3 682), χ 2=180.032, P<0.001]. Five cases in the sedation group developed iatrogenic colonic perforation (ICP), with none in the non-sedation group. Conclusions:The application of sedation in colonoscopy is increasingly popular. Sedation can significantly improve CIR in colonoscopy, while it has no positive influence on PDR. Meanwhile, sedation increases the medical expense and may result in higher ICP rate.

Objective:To investigate the value of sedation in colonoscopy.Methods:A retrospective cohort study of colonoscopy procedures was performed in our institution. Inclusion criteria: (1) colonoscopy procedures were performed by well-trained gastrointestinal surgeons our institution; (2) medical records were complete and colonoscopy was documented properly by notes, videos, photographs, and traceable pathological reports. Those with incomplete records or performed in other institution were excluded. According to above criteria, clinical data of 49 057 cases of clinic and hospitalization receiving diagnostic or therapeutic colonoscopyat Department of Gastric and Colorectal Surgery, Daping Hospital from July 2007 to February 2017 were collected. Among them, there were 24 638 (50.2%) males and 24 419 females, with mean age of (50.6±14.1) (4 to 98) years. Based on the application of sedation during colonoscopy, patients were divided into the sedation group (39 412 cases, 80.3%) and the non-sedation group (9 645 cases, 19.7%). Clinical characteristics of two groups were compared.Results:The sedation rate increased from 45.6% (369/810) to 94.8% (917/967) from 2007 to 2017. As compared to non-sedation group, a higher proportion of females [51.0% (20 095/39 412) vs. 44.8% (4 324/9 645), χ 2=117.422, P<0.001] and younger median age (50.0 years vs. 51.0 years, Z=-4.774, P<0.001) were found in the sedation group, whose differences were statistically significant. In all the 9645 cases in the non-sedation group, about 5.5% (534) of them terminated the examination because of unbearable discomfort, including 244 (4.6%) males and 290 (6.7%) females (χ 2=20.522, P<0.001). Among all the screening population who were ≥50 years old, there was no significant difference in the polyp detection rate (PDR) between the sedation group and the non-sedation group [26.7% (4 737/17 753) vs. 27.4% (1 093/3 984), χ 2=0.937, P=0.330]. The cecal intubation rate (CIR) in the sedation group was significantly higher than that in the non-sedation group [(85.2% (14 422/16 933) vs. 76.1% (2 803/3 682), χ 2=180.032, P<0.001]. Five cases in the sedation group developed iatrogenic colonic perforation (ICP), with none in the non-sedation group. Conclusions:The application of sedation in colonoscopy is increasingly popular. Sedation can significantly improve CIR in colonoscopy, while it has no positive influence on PDR. Meanwhile, sedation increases the medical expense and may result in higher ICP rate.

Objective To evaluate the correlation between cerebral blood flow perfusion and memory impairment in patients with severe stenosis of vertebral basilar artery (VBA).Methods 62 cases of patients with VBA stenosis diagnosed by digital subtraction angiography(DSA) in Beijing Tiantan Hospital from September 2016 to March 2017 were enrolled.Mental State Examination (MMSE),Clinical Memory Scale (CMS) test and CT perfusion(CTP) was performed.All patients were divided into memory normal group(n=24,including 1 excellent case,6 above normal cases,and 14 normal cases) and memory impairment group(n =38,including 18 below normal cases,12 periphery cases,8 impaired cases) according to CMS.The ratios of side-to-side period were compared between bilateral mesial temporal lobe and anterior circulation area.The relative time to peak (rTTP),relative mean transit time(rMTY),relative cerebral blood flow(rCBF) and relative cerebral blood volume (rCBV) were calculate.Results The incidence of CTP decompensation in the medial temporal lobe was higher than that in the patients with memory impairment(P＜0.05).The difference of rTTP and rMTT value between the two groups in the bilateral medial temporal lobes was statistically significant (rTFP:(1.131 ±0.037),(1.437±0.139),t=10.520,P＜ 0.05);rMTT:(1.081 ±0.059),(1.281 ±0.174),t=5.423,P＜0.05).Conclusion The patients with VBA severe stenosis are more likely to get memory impairment due to cerebral hypoperfusion.