Objective To establish the characteristic atlas of Shexiang Jiegu Capsule and determine the contents of seven active components （hydroxysafflor Yellow A, paeoniflorin, ferulic acid, naringin, ligustilide, catechin, epicatechin）. Methods Octadecyl silane bonded silica gel was used as the filling agent, the mobile phase was composed of methanol-0.05% phosphoric acid by gradient elution, the detection wavelength was 245 nm, flow rate was 1.0 ml/min, column temperature was 30℃. The similarity of the fifteen batches of sample was evaluated in line with the TCM Chromatographic Fingerprint （2012 edition）, and the contents of seven active components were determined. Results The HPLC fingerprint of Shexiang Jiegu Capsules was established. The similarity of fingerprint between fifteen batches of samples and control fingerprint was between 0.893 and 0.992. The results of methodological investigation for the determination of seven active components in fifteen batches of samples all met the requirements. Conclusion The established characteristic atlas of Shexiang Jiegu Capsules had high specificity and good repeatability, which could provide scientific basis for quality control of Shexiang Jiegu Capsules.

Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1％triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r＞0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7％(RSD=1.3％),102.6％(RSD=1.1％)and 100.9％(RSD=1.1％),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.

ObjectiveTo investigate the effect and possible mechanism of Sishenwan in ameliorating visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency. MethodForty male SPF-grade rats were randomly assigned into five groups： blank control， model， low- （3.51 g·kg^-1） and high-dose （7.02 g·kg^-1） Sishenwan， and Peifikang （0.54 g·kg^-1） groups. Except the blank control group， the other groups underwent maternal separation stress and Sennae Folium decoction gavage for the modeling of IBS-D due to spleen-kidney Yang deficiency. After corresponding drug interventions， the general conditions of the rats were observed， and the number of defecation pellets within 6 h and the minimum threshold of abdominal withdrawal reflex （AWR） were measured. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of tumor necrosis factor （TNF）-α， gastrin （GAS）， corticosterone （CORT）， and adrenocorticotropic hormone （ACTH）. Hematoxylin-eosin （HE） staining was employed to observe pathological changes in the colon tissue. Toluidine blue staining was used to assess mast cell degranulation in the colon tissue. Western blot was performed to determine the protein levels of p38 mitogen-activated protein kinase （MAPK）， c-Jun N-terminal kinase （JNK）， transient receptor potential vanilloid 1 （TRPV1）， and protease-activated receptor 2 （PAR2） in the colon tissue. Immunohistochemistry was employed to measure the protein level of TRPV1 in the colon tissue， and immunofluorescence was used to detect the positive expression of substance P （SP） and calcitonin gene-related peptide （CGRP） in the colon tissue. ResultCompared with the blank control group， the model group showed increased number of defecation pellets within 6 h （P<0.01）， decreased minimum threshold of AWR （P<0.01）， elevated serum TNF-α level （P<0.01）， lowered levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， increased mast cell degranulation rate （P<0.01）， increased positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and upregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.01）. Compared with the model group， the high-dose Sishenwan group showed increased minimum threshold of AWR （P<0.01）， reduced defecation frequency in both the high-dose Sishenwan and Peifikang groups （P<0.05， P<0.01）， lowered TNF-α level （P<0.05， P<0.01）， elevated levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， decreased mast cell degranulation rate （P<0.01）， reduced positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and downregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.05， P<0.01）. ConclusionSishenwan can ameliorate visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome due to spleen-kidney Yang deficiency by regulating the p38 MAPK/JNK/TRPV1 signaling pathway.

Objective To explore the effect and safety of calcium dibutyryl adenosine cyclophosphate(dbcAMP-Ca)combined with metoprolol in the treatment of older adults with heart failure combined with arrhythmia.Methods A total of 102 elderly patients with heart failure combined with arrhythmia were enrolled in our hospital between February 2021 and April 2023.The list of patients enrolled was entered into a random database by independent staffs not involved in the study and random assignment sequences were generated by the SAS9.4 software.Then,the 102 elderly patients were divided into a control group(n=51)and an experimental group(n=51).Patients in the control group were given metoprolol at an initial dose of 6.25 mg/d,which was gradually increased to the target dose of 25 mg/d.Patients in the experimental group were given 40 mg of dbcAMP-Ca once a day via intravenous drip in addition to the treatment given to the control group.Both groups were treated for 4 weeks.The rate of effective response to clinical treatment(the number of cases achieving significant effects and those achieving some effects divided by the total number of cases in the group)was defined as the main outcome index.Secondary indexes included cardiac function,heart rate variability,exercise ability,hemorheology,myocardial injury indexes,inflammatory indexes,and the occurrence of adverse reactions.Results The rate of effective response to clinical treatment was higher in the experimental group than that in the control group(94.12%[48/51]vs.78.43%[40/51],P<0.05).After treatment,the left ventricular end-diastolic and end-systolic dimensions(LVEDD and LVESD)and the interventricular septal thickness(IVS)were lower in the experimental group than those in the control group,while the left ventricular ejection fraction(LVEF)and the stroke volume(SV)were higher in the experimental group than those in the control group(P<0.05).In terms of heart rate variability after treatment,the standard deviation of all the normal-to-normal intervals/the average of all the normal-to-normal intervals(SDNN/SDANN),the percentage of NN50 in the total number of normal-to-normal intervals(PNN50% ),and the root mean square of the differences between adjacent normal-to-normal intervals/root mean square differences of successive R-R intervals(RMSSD)were higher in the experimental group than those in the control group(P<0.05).In terms of exercise capacity after treatment,the subjects in the experimental group covered more distance in the 6-min walk test than those in the control group did(P<0.05).In terms of the hemorheology indexes after treatment,the levels of platelet aggregation rate(PAgT),fibrinogen(FIB),erythrocyte sedimentation rate(ESR),and whole blood viscosity(ηb)were lower in the experimental group than those in the control group(P<0.05).In terms of the myocardial injury indexes after treatment,the levels of serum N-terminal pro-brain natriuretic peptide(NT-pro BNP)and cardiac troponin I(cTnI)were lower in the experimental group than those in the control group,while the levels of insulin-like growth factor 1(IGF-1)and cardiotrophin 1(CT-1)were higher in the experimental group than those in the control group(P<0.05).In terms of the inflammatory indexes after treatment,the levels of interleukin-6(IL-6),high-sensitive C-reactive protein(hs-CRP),and tumor necrosis factor-α(TNF-α)were lower in the experimental group than those in the control group(P<0.05).The incidence of adverse reactions in the experimental group(9.80% )and that in the control group(7.84% )were comparable(P>0.05).Conclusion The use of dbcAMP-Ca in addition to metoprolol can effectively improve cardiac function,heart rate variability,and exercise tolerance,while inhibiting inflammatory response in elderly patients with heart failure combined with arrhythmia,with high medication safety.The combination medication shows better safety and therapeutic effects than those of metoprolol used alone.

Objective:To evaluate the efficacy and safety of ultrasound-guided high intensity focused ultrasound(HIFU)on pain intensity,pain sensation and overall survival in patients with advanced pancreatic cancer. Methods:Clinical data of advanced pancreatic cancer patients treated by HIFU were collected from the patients enrolled during August 2020 to September 2022 at the second department for oncology of Yueyang Hospital of Integrated Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine.In this study,SPSS 26.0 software was used for the statistical analysis of NRS score and BPI score.The Kaplan-Meier survival analysis method was applied to calculate the median overall survival(OS)and then the survival curve was drawn.At the same time,the incidence of related adverse reactions during and after HIFU treatment was counted. Results:(1)Among the 45 patients,30 patients received HIFU combined with chemotherapy,and the other 15 patients only received HIFU.(2)Among the 45 patients,32 patients had pain relief after HIFU treatment,and the NRS score kept decreased across 1 week,2 weeks,3 weeks and 1 month after HIFU treatment(P＜0.05).The pain sensation score of BPI scale also decreased correspondingly,and the difference was statistically significant(P＜0.05).(3)The median OS of 45 patients was 11.1 months(95％Cl:9.30-1 2.90),of which 30 patients treated with HIFU combined chemotherapy had a median OS of 12.4 months(95％Cl:9.1 8-15.62),and 15 patients treated with HIFU only had a median OS of 4.6 months(95％Cl:1.11-8.10).(4)No serious adverse events were observed in all patients during and after HIFU treatment.Only 5 patients had asymptomatic mild elevation of blood amylase,and the incidence of mild adverse reactions was 11.1％. Conclusion:HIFU can effectively relieve pain and prolong the median survival time in patients with advanced pancreatic cancer.

[Abstract] Objective: To construct and purify the recombinant bispecific antibody (BsAb) targeting PD-1 and CD19 and evaluate its activity. Methods: With pCAR1 plasmid as the vector, the eukaryotic expression vector of anti-PD-1/CD19 BsAb was constructed by molecular cloning technology, and then transfected into mammalian cell line CHO-S by PEI reagent for transiently expressing antibody. The BsAb was purified by Affinity chromatography and then identified by SDS-PAGE and WB. The blocking activity of BsAb on PD-1/PD-L1 in vitro was detected by Luciferase reporter gene assay. The activity of antibody (BsAb)-dependent cell (PBMC)-mediated cytotoxicity (ADCC) in vitro was evaluated by lactate dehydrogenase (LDH) cytotoxicity assay. Results: The double plasmid eukaryotic expression vector pCAR1-19X3 was successfully constructed, and anti-PD-1/CD19 BsAb was successfully expressed in CHO-S cells, named pCAR1-19X3-TY. pCAR1-19X3-TY could effectively block the binding of PD-1 to its ligand PD-L1 in vitro, and the EC50 based on the dose-response curve was 0.306 μg/ml. ADCC results showed that pCAR1-19X3-TY could mediate the cytotoxicity of PBMC against Raji cells, and the curve showed a linear upward trend; when the effect/target ratio was 50∶1, the target cell lysis rate of pCAR1-19X3-TY was (38.9±0.3)%, which was not significantly different from that of the positive treatment group (46.7±4.9)% (P>0.05), but significantly higher than that of the negative control group (1.2±0.1)% (P<0.05). Conclusion: The recombinant anti-PD-1/CD19 BsAb can effectively block the binding of PD-1 and PD-L1 and activate PBMC mediated cytotoxicity against Raji cells. pCAR1-19X3-TY has the potential application value in the treatment of B-cell malignant tumor.

Objective:To study the effect of COVID-19 on pregnancy outcomes and neonatal prognosis in Hubei Province.Method:s A retrospective comparison of the pregnancy outcomes was done between 16 women with COVID-19 and 45 women without COVID-19. Also, the results of laboratory tests, imaging examinations, and the 2019 novel coronavirus (2019-nCoV) nucleic acid test were performed in 10 cases of neonatal delivered from women with COVID-19.Result:s (1) Of the 16 pregnant women with COVID-19, 15 cases were ordinary type and 1 case was severe type. No one has progressed to critical pneumonia.The delivery method of the two groups was cesarean section, and the gestational age were (38.7±1.4) and (37.9±1.6) weeks,there was no significant difference between the two groups ( P>0.05). Also, there wee no significant differences in the intraoperative blood loss and birth weight of the newborn between the two groups (all P>0.05). (2) Ten cases of neonates delivered from pregnant women with COVID-19 were collected. The 2019-nCoV nucleic acid test were all negative.There were no significant differences in fetal distress, meconium-stained amniotic fluid, preterm birth, and neonatal asphyxia between the two groups (all P>0.05).(3) In the treatment of uterine contraction fatigue, carbetocin or carboprost tromethamine was used more in cesarean section for pregnant women with COVID-19 (1.3±0.6), compared with Non-COVID-19 group (0.5±0.7),the difference was statistically significant ( P=0.001). Conclusions:If there is an indication for obstetric surgery or critical illness of COVID-19 in pregnant women, timely termination of pregnancy will not increase the risk of premature birth and asphyxia of the newborn, but it is beneficial to the treatment and rehabilitation of maternal pneumonia. Preventive use of long-acting uterotonic agents could reduce the incidence of postpartum hemorrhage during surgery. 2019-nCoV infection has not been found in neonates delivered from pregnant women with COVID-19.

Objective: To investigate the timing of the laparoscopic cholecystectomy after percutaneous transhepatic gallbladder drainage for acute pyogenic cholecystitis in the advanced age. Methods: The clinical data for 56 advanced age patients with acute pyogenic cholecystitis in the Department of Hepatobiliary Surgery, the 900th Hospital of the Joint Logistics Support Force of People′s Liberation Army from January 2018 to February 2019 were retrospectively analyzed. There were 31 males and 25 females, aged from 70 to 86 years, with average age was (75.52±3.57) years. According to the percutaneous transhepatic gallbladder drainage(PTGD) after laparoscopic cholecystectomy(LC) time interval, all patients were divided into three groups. Patients in the group A(n=12), B(n=21), and C (n=23) performed LC were within 2 months, during 2-4 months, and during 4-6 months, retrospectively. Observation indicators: (1) Surgical situations. The operation and postoperative basic condition of the three groups were compared. (2) Follow-up situations. Patients were followed-up by outpatient examination or telephone interview to detect the postoperative complication in the postoperative three months up to June 2019. Measurement data with normal distribution were represented as (Mean±SD), and comparison multiple groups was done using single factor analysis of variance (AVONA test) , and comparison between groups was done using the t test, and comparison of multiple groups in pairs was done using the SNK-q test, and hierarchical data were analyzed using Kruskal-wallis H test. Count data were analyzed using the chi-square test or Fisher exact probability. Results: (1) Surgical situations: the thickness of gallbladder wall before LC, the rates of converting to laparotomy, the volume of intraoperative blood loss, the operation duration, and the duration of postoperative hospital stay were (0.57±0.04) cm, 50.0%, (95.83±11.45) ml, (107.50±21.90) min, (5.67±3.40) d in the group A, and (0.43±0.03) cm, 9.5%, (69.52±24.59) ml, (71.43±12.16) min, (3.76±2.61) d in the group B, and (0.43±0.05) cm, 39.1%, (68.64±21.89) ml, (77.95±12.88) min, (5.05±2.95) d in the group C, respectively, showing significant differences in the above indicators between the three groups (P<0.05). The thickness of gallbladder wall before LC, the volume of intraoperative blood loss, the operation duration, those in group A were higher than the group B and C (P<0.05), and with no statistically significant different between the group B and C (P>0.05). The rates of converting to laparotomy, the duration of postoperative hospital stay in group B were better than the group A and C (P<0.05), and with no statistically significant different between the group A and C (P>0.05). The thickness of gallbladder wall before LC, the volume of intraoperative blood loss, the operation duration, and the duration of postoperative hospital stay were (0.43±0.03) cm, (46.67±9.82) ml, (67.69±7.77) min, (2.64±0.58) d in the gallbladder wall thickness of successful LC patients, and (0.52±0.04) cm, (123.53±17.30) ml, (134.12±25.51) min, (8.47±0.80) d in the laparotomy patients, respectively, showing significant differences in the above indicators between the two groups (P<0.05). (2) Follow-up situations: 56 patients were followed up and without perioperative death. No complications occurred after 3 months of follow-up. Conclusion Elective surgery that is performed in 2-4 months after PTGD for patients with acute pyogenic cholecystitis in the advanced age can reduce the volume of intraoperative blood loss and the rates of converting to laparotomy, shorten the operation duration and the duration of postoperative hospital stay, which is beneficial to the recovery of patients.

Objective To investigate the theory of mind ( TOM) and eye basic emotion recognition in benign epilepsy children with centrotemporal spikes( BECT) . Methods Totally 51 BECT patients( BECT group) and 51 healthy controls( control group) were studied by Yoni task and Eye Basic Emotion Discrimi-nation Task (EBEDT). Results ①Compared with healthy controls,BECT got significantly lower score ((54. 02±6. 03) vs (58. 04±5. 41),F(1,100)=10. 34,P<0. 05))in Yoni task,especially in affective(hot) TOM .②There was no significant difference between the BECT group(M(P25,P75):103(96,108)) and the control group(M(P25,P75):105(96,110))in the total score of Eye Basic Emotion Discrimination Task(Z=-1. 37,P>0. 05),but got significantly lower score in recognizing sadness(M(P25,P75):16(14,17) vs 18 (15,19),Z=-3. 05,P<0. 05)and fear(M(P25,P75):15(14,17) vs 16(16,18),Z=-2. 21,P<0. 05).③Pearson or Spearman correlation analysis showed that there was no significant correlation between the total score of TOM and the age,age of onset, education,seizure total number,MMSE,the Digital Span test, the verbal fluency test and eye basic emotion recognition ( r=-0. 257-0. 908,all P>0. 05) . Conclusion BECT children have impairments in sadness and fear emotion recognition and TOM aspects.

Objective To investigate the ability of decision-making under risk condition in benign epilepsy children with centrotemporal spikes (BECT).Method Seventy-eight BECT patients and seventyfive healthycontrols were studied by Iowa Gambling Task (IGT) with inexplicit probability and Game of Dice Test (GDT) with explicit probability.Results (1) There was a significant difference in IGT task scores between the two group (t=-2.56,P＜0.05).The total number of advantageous choices in IGT were lower in BECT group (49.35±5.38) than that in healthy control group (52.24±6.23).BECT group (-1.41 ± 10.60) performed worse on task than healthy control group (4.43±11.88),and the difference was statistically significant (t=-3.21,P＜0.05).The control group scored higher on Blockl,Block4 and Block5 than that of BECT group (P＜0.05).(2) There was no significant difference between the BECT group (4.42±7.74) and the control group(5.49±6.81) in the GDT test scores (t=-0.91,P=0.37).(3) Pearson correlation analysis showed that there was no significant correlation between the age,age of onset,education,seizure frequency and onset duration and the score of IGT and GDT (r =-0.091-0.274,all P ＞ 0.05).Conclusion There is no significant decision-making disability in children with BECT under the condition of certain risk probability,while there is significant impairment under the condition of uncertain risk probability.The decision-making disability may be associated with impaired frontal lobe function.