Objective To analyze the chemical components of Xiaoshi Lidan pills by using UPLC-MS/MS and explore the mechanism of Xiaoshi Lidan pills in the treatment of cholelithiasis through network pharmacology and molecular docking techniques.Methods The pharmacologically active components of Xiaoshi Lidan pills were analyzed through UPLC-MS/MS and compared with standard references.Potential targets of these components were obtained by searching the TCMSP and ETCM databases,and disease-related targets for cholelithiasis were identified using the DisGeNET database.The overlapping targets were used to construct a protein-protein interaction(PPI)network in the String database,and a"drug-component-target"network was built using Cytoscape 3.9.1.GO and KEGG enrichment analyses were performed for the core targets.Finally,the top 5 compounds with strong activity were selected as ligands for molecular docking with the screened disease target genes.The anti-inflammatory activity was verified by RAW264.7 cells,and the mRNA expression of TNF-a and other inflammatory factors was detected by RT-PCR.Results UPLC-MS/MS identified 30 compounds in Xiaoshi Lidan pills,among which baicalin,quercetin,wogonin,baicalein-7-O-glucuronide,and emodin were identified as key components of Xiaoshi Lidan pills.Network pharmacology identified 107 targets associated with cholelithiasis,with Alb,TP53,ESR1,TNF,and INS identified as core targets.GO analysis indicated the involvement in inflammation response and steroid binding,while KEGG pathways were primarily related to lipid metabolism,atherosclerosis,and the TNF signaling pathway.Molecular docking analysis and anti-inflammatory screening in vitro showed that Xiaoshi Lidan pills exhibited certain anti-inflammatory activity by regulating inflammatory factors such as TNF and inhibiting NO production through baicalein,quercetin,emodin and other components.Conclusion Xiaoshi Lidan pills exerts its therapeutic effect on cholelithiasis by regulating TNF-related pathways through components such as baicalin,thereby inhibiting the inflammatory response.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective:To investigate the application value of laparoscopic pancreatic tumor enucleation (LapEN).Methods:The retrospective and descriptive study was conducted. The clinical data of 47 patients who underwent LapEN in Second Hospital of Hebei Medical University from September 2016 to June 2022 were collected. There were 18 males and 29 females, aged (49±12)years. Observa-tion indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative recovery; (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 47 patients underwent LapEN successfully, with the operation time as (135±19)minutes and the volume of intraoperative blood loss as 100(50,100)mL. (2) Postoperative complications. Of the 47 patients, there were 12 patients with postoperative pancreatic fistula, 3 patients with postoperative abdominal infection, 1 case with postoperative hemorrhage, 1 case with postoperative gastric emptying disorder. (3) Postoperative recovery. Of the 47 patients, there were 13 cases with pancreatic solid pseudopapillary neoplasm, 12 cases with insulinoma, 11 cases with pancreatic serous cystadenoma, 7 cases with pancreatic intraductal papillary mucinous neoplasm (branched type), 4 cases with pancreatic mucinous cyst-adenoma. The tumor diameter of 47 patients was 1.9(1.6,2.3)cm and all patients with R 0 resection. There was no patient with perioperative death in the 47 patients. The postoperative duration of hospital stay and total hospital expenses of 47 patients was (13±4)days and (6.8±1.2) ten thousand yuan, respectively. (4) Follow-up. All 47 patients were followed up for 14(range, 8?18)months. None of the 47 patients had new onset diabetes or situations required postoperative exocrine replacement therapy, and no patient died. Conclusion:LapEN is safe and feasible for patients with pancreatic benign tumor or low potential malignancy.

Objective:To evaluate the relationship between regional coronary flow reserve (CFR) obtained from cadmium-zinc-telluride SPECT(CZT SPECT) myocardial functional perfusion imaging (MFPI) and invasive fractional flow reserve (FFR) measured during coronary angiography (CAG) and its clinical value in guiding coronary interventions.Methods:Forty-two patients (30 males, 12 females, age (63.3±9.8) years) who completed CZT SPECT MFPI in the First Affiliated Hospital of Nanjing Medical University from June 2022 to September 2022 and underwent CAG within 3 months were included retrospectively. The concordance of CFR and FFR for diagnosing myocardial ischemia (CFR<2.0 and FFR<0.8) was calculated at the vascular level. The diagnostic efficacy of coronary stenosis≥70% for decreased myocardial blood flow (CFR<2.0) was calculated. Kappa test was used to analyze the data. Results:A total of 126 major coronary arteries were identified in 42 patients, of which 30(23.8%) had a CFR<2.0 by CZT SPECT and 33(26.2%) had stenosis≥70% in CAG. A total of 32 coronary vessels were performed with MFPI CFR and FFR measurements, of which 6 were both decreased and 21 were both normal, so the concordance rate was 84.4%(27/32)( Kappa=0.612, P<0.001). Among 33 coronary vessels with stenosis≥70%, 13 were with CFR≥2.0. Among 30 coronary vessels with CFR<2.0, 10 were with stenosis<70%. When using stenosis≥70% to diagnose CFR decreasing, the sensitivity was 66.7%(20/30), specificity was 86.5%(83/96), positive predictive value was 60.6%(20/33), negative predictive value was 89.2%(83/93), and accuracy was 81.7%(103/126). Conclusions:The concordance between CFR and FFR for the diagnosis of myocardial ischemia is good. Nearly 1/3 of the coronary arteries with decreased CFR have stenosis<70%, whereas nearly 40% of the coronary arteries with stenosis≥70% are not result in myocardial ischemia. Regional CFR determined by CZT SPECT may have potentially significant clinical value in the diagnosis of coronary artery disease and decision-making of coronary intervention.

Objective:To study the safety and therapeutic effects of the modified pancreaticogastrostomy based on the concept of " Hong's one-stitch method" in digestive tract reconstruction in pancreatic surgery.Methods:The clinical data of 44 patients who underwent modified pancreaticogastresstomy at the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University from May 2022 to October 2022 were analyzed retrospectively. There were 23 males and 21 females , with a median age of 54 years old (range 18 to 70 years old). The operation time, intraoperative blood loss, postoperative condition and complications were analysed.Results:All the 44 patients completed the operation successfully. There were 29 patients who underwent laparoscopic pancreaticoduodenectomy, 11 patients laparoscopic duodenum-preserving pancreatic head resection, 1 patient laparoscopic central pancreatectomy, and 3 patients open pancreaticoduodenectomy. The time required for the pancreaticogastrostomy was (15.4±1.0) min in laparoscopic surgery, and (9.1±0.5) min in open surgery. There were 2 patients who developed grade A pancreatic fistula (4.55%, 2/44) and 7 patients gastric emptying disorder (15.91%, 7/44). There were no grade B or C pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, abdominal infection, postoperative bleeding and perioperative death.Conclusion:The modified pancreaticogastrostomy for digestive tract reconstruction in pancreatic surgery was safe and reliable. It effectively reduced the incidence of postoperative pancreatic fistula and improved prognosis of patients.

Objective:To study the clinical characteristics and management strategies of late bleeding after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 58 patients with post-pancreaticoduodenectomy hemorrhage (PPH) admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from March 2018 to March 2022 were retrospectively analyzed, including 42 males and 16 females, aged (61.88±11.02) years old. According to the occurrence of intra-abdominal erosion factors (e.g., pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, intra-abdominal abscess), patients were divided into the erosion group ( n=42) and non-erosion group ( n=16). All patients underwent standard lymphadenectomy. Clinical data including the PPH time-point, occurrence of rebleeding, and treatment outcomes were accessed. The management strategies of PPH in the two groups of patients were analyzed. Results:The PPH time-point in the erosion group and non-erosion patients was 8.00 (5.00, 19.25) d and 21.50 (12.75, 26.75) d, respectively ( P=0.001). PPH can occurred within one month after surgery in both erosion and non-erosion groups. In the erosion group, 31 cases (73.81%, 31/42) were treated by re-operation, two (4.76%, 2/42) by interventional radiology and nine (21.43%, 9/42) with conservative protocol, respectively. In the non-erosion group, five cases (31.25%, 5/16) were treated by re-operation, seven (43.75%, 7/16) by interventional radiology and four (25.00%, 4/16) with conservative protocol, respectively. The incidence of re-bleeding is higher in the erosion group [47.6% (20/42) vs 12.5% (2/16), P<0.05]. Clinical manifestations, sites and severity of bleeding, and treatment outcomes were also different in the erosion and non-erosion groups (all P<0.05). Conclusions:The occurrence of intra-abdominal erosion factors can affect the clinical characteristics and treatment strategy of late bleeding after laparoscopic pancreaticoduodenectomy. Surgery remains the treatment of choice for post-pancreaticoduodenectomy hemorrhage either as an urgent or last resort.

Objective:To improve the differential awareness of lead porsoning.Methods:A case with stomachache, anemia, myasthenia, and abnormal urine color was described. The diagnosis and treatment were analyzed and discussed.Results:A middle-aged female was admitted with a 9-month medical history, compalnied with rash, stomachache. She also had evidence of hemolytic anemia,nervous system and kidneys imvolvement, and Lab test showed a significantly elevated blood lead level. It was considered to be in line with multiple organ system damage caused by lead poisoning.Conclusion:Lead poisoning can mimic the clinical presentations of rheumatic diseases, resulting in multiple system ivolvement. When the patient's clinical manifestation cannot be fully explained, some special situations should be considered, such as toxic testing.

Objective:To explore the feasibility of a stable pig-to-monkey orthotopic liver transplantation (LT) model and provide a favorable experimental tool for preclinical studies of xenotransplantation.Methods:In this retrospective analysis, the authors reviewed the perioperative conditions and outcomes of 7 pig-to-monkey orthotopic liver transplants performed by a xenotransplantation research team of Second Xiangya Hospital.Gene-edited Banna miniature pigs were selected as donors and rhesus monkeys with similar anatomical characteristics, physiology, biochemistry and immune mechanism to humans were selected as recipients for pig-monkey xenogeneic orthotopic LT.Based upon classic transplantation procedures, whole liver xenogeneic orthotopic transplantation was performed.Surgical processes were modified for minimizing intraoperative hemorrhage and shortening anhepatic period.A bile duct drainage tube was implanted for observing bile secretion.ATG + anti-CD20 + snake venom factor and FK-506 were utilized for immunoinduction pre-operation while tacrolimus, mycophenolate mofetil (MMF) and methyl prednisolone for postoperative immunomaintenance therapy.Antibiotics and antiviral agents were also applied and thrombin complex for improving coagulation functions.Results:All procedures were successfully completed.After the stability and maturity of our model, in case No.7, donor's acquisition operative duration was 42 min without heat ischemic time, donor's trimming time 87 min, donor cold retention time 128 min, recipient's operative duration 123 min and anhepatic phase 27 min.Subhepatic inferior vena cava was occluded for 38 min.Blood loss was around 10 ml.And 4/7 models survived post-operation and the longest survival time was 27 h. Among 3 non-survival cases, the causes were anesthesia accident (n=1) and immaturity of early operation (n=2). Model No.7 had a biliary secretion volume of 86 ml post-operation.Conclusions:Qualified donor acquisition, high-quality vascular anastomosis, intraoperative reduction of blood loss, shortening of anhepatic period, strict fluid replenishing and careful monitoring are essential for boosting the success rate of pig-monkey liver xenotransplantation model.Optimization of donor gene combination and advanced immunosuppression protocol help to further achieve the long-term survival of pig-monkey liver xenotransplantation model.

Liver transplantation is a curable therapy to save the life of patients with end-stage liver diseases of different causes. The serious shortage of liver donors led to the death of a large number of patients with end-stage liver disease. Genetic-engineered pigs used for xenotransplantation are one of the potential solutions to alleviate the liver donor shortage, but currently clinical application of such xenogeneic liver grafts is hindered by acute rejection, thrombocytopenia, and coagulation dysfunctions in patients. The development of genetic-engineering technology and the application of new immunosuppressants have controlled the acute rejection of liver xenotransplantation to some extent. However, acute humoral rejection may become another major issue for the long-term graft failure. This review summarized and discussed the potential and underlying mechanisms and preventive measures of acute humoral rejection in liver xenotransplantation.

Objective:To study the optional timing of removal of abdominal drains after laparoscopic pancreaticoduodenectomy (LPD) based on the enhanced recovery after surgery (ERAS) concept versus conventional practice.Methods:The clinical data of patients who underwent LPD at the Second Hospital of Hebei Medical University and the First Hospital of Hebei Medical University from January 2020 to June 2021 were retrospectively analyzed. Of 127 patients included in this study, there were 74 males and 53 females, with age of (58.68±8.65) years old. Then patients were divided into two groups according to the timing of removal of abdominal drains based on the ERAS concept (the ERAS group, n=61), and conventional clinical practice (the control group, n=66). The abdominal drains in the ERAS group was removed based on 2 criteria: (1) no discharge of bile, gastrointestinal contents, pus, and active bleeding in the abdominal drains on the first day after operation; (2) amylase in abdominal drainage fluid was less than 5 000 U/L on the first day after operation. The abdominal drains in the control group was removed after meeting the following criteria: (1) no discharge of bile, gastrointestinal contents, pus, and active bleeding in the abdominal drains; (2) from the first day after operation, amylase levels in the drain fluid was measured once everyday, and the concentrations of the amylase were less than 5 000 U/L for 2 consecutive days; (3) the volume of drainage was less than 100 ml/24 h. The postoperative recovery and other clinical data of the two groups were also compared. Results:LPD was successfully performed in the 2 groups, and there was no perioperative death. The timing of removal of abdominal drains [1 vs. 7(5, 9) d], the first passage of flatus [3(2, 4) vs. 3(3, 5) d] and the postoperative hospital stay [14(10, 18) vs. 17(14, 22) d] in the ERAS group were significantly shorter than the control group, and the hospitalization cost was also significantly less [10.33(9.64, 11.52) vs. 11.22(10.38, 13.58) wan yuan] (all P<0.05). Conclusion:The ERAS concept in guiding the timing of removal of abdominal drains after LPD was safe and feasible. The enhanced recovery after surgery concept is worthy of further promotion and application.