ObjectiveTo observe the effect of Shenling Baizhusan on the intervention of the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway by regulating ferroptosis in rats with alcoholic liver injury. MethodForty SD rats were randomly divided into model group， polyene phosphatidylcholine group， and high， medium， and low-dose Shenling Baizhusan groups， with 8 rats in each group. Another 8 SD rats were taken as blank group. The model group， polyene phosphatidylcholine group， high， medium， and low-dose Shenling Baizhusan groups were given 10 mL·kg^-1 liquor by gavage for modeling， and the blank group was given equal volume of distilled water by gavage. After 4 h of daily alcoholic administration， 143.64 mg·kg^-1 of polyene phosphatidylcholine group was given to the polyene phosphatidylcholine group， 15， 7.5， 3.75 mg·kg^-1 of Shenling Baizhusan were given to Shenling Baizhusan high， medium， and low-dose groups， respectively， and the blank group and the model group were given equal volume of distilled water. The gavage lasted for 6 weeks. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， glutamyl transpeptidase （GGT）， total cholesterol （TC）， and triglyceride （TG） were detected by automatic biochemical analyzer. The levels of tumor necrosis factor-α （TNF-α） and interleukin-β （IL-β） were detected by the enzyme-linked immunosorbent assay （ELISA）. The levels of lipopolysaccharide （LPS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， and Fe⁺ were detected by biochemical assay. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The mRNA expression levels of Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， ferritin heavy polypeptide 1 （FTH1）， and nuclear factor-κB （NF-κB） were detected by Real-time polymerase chain reaction （Real-time PCR）. The protein expression levels of Nrf2， HO-1， GPX4， FTH1， p65， and phosphorylation （p）-p65 were detected by Western blot. ResultAs compared with the blank group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the model group were significantly increased （P<0.05）. The liver showed obvious steatosis， with a large number of fat deposition， the oxidative stress and inflammatory factors were significantly increased （P<0.05）， and the level of Fe⁺ was significantly increased in model group （P<0.05）. The protein expression levels of Nrf2， HO-1， GPX4， and FTH1 was significantly down-regulated （P<0.05）， and those of p65 and p-p65 was significantly up-regulated in the model group （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly down-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly up-regulated （P<0.05）. As compared with the model group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the high-dose and medium-dose Shenling Baizhusan groups were significantly decreased （P<0.05）， liver steatosis was significantly improved， fat deposition was significantly reduced， oxidative stress and inflammatory factors were significantly decreased （P<0.05 ）， and Fe⁺ level was significantly decreased （P<0.05）. In the high-dose and medium-dose Shenling Baizhusan， the protein expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and those of p65， p-p65 were significantly down-regulated （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly down-regulated （P<0.05）. ConclusionShenling Baizhusan can effectively reduce liver injury in rats with ALD， regulate steatosis and fat deposition， and play an antioxidant and anti-inflammatory role in the liver. Its mechanism may be related to the inhibition of ferroptosis in hepatocytes by up-regulating the Nrf2 signaling pathway to improve oxidative stress

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

BACKGROUND: Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. METHODS: This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. RESULTS: At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. CONCLUSIONS: Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. REGISTRATION ClinicalTrials.gov, NCT04214951.
Adult ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin/adverse effects* ; Prospective Studies ; Recombinant Fusion Proteins ; Receptors, Fc/therapeutic use* ; Receptors, Thrombopoietin/therapeutic use* ; Thrombocytopenia/chemically induced* ; Benzoates/adverse effects* ; Hydrazines/adverse effects*

Objective:To explore the clinical efficacy of liver transplantation for Wilson's disease(WD).Methods:From January 1999 to November 2021, clinical data were retrospectively reviewed for 16 recipients with WD undergoing liver transplantation.There were 9 males and 7 females with an age range of 29.5(14~54)years.They were followed up by telephone, outpatient services and hospitalization.The starting point of follow-up was operation date.And recipient death was an endpoint.Postoperative survival, improvement of neuropsychiatric symptom, changes of corneal K-F ring, altered levels of liver function and serum copper-protein at Month 1 post-operation were observed.The follow-up deadline was November 24, 2021.Results:15 recipients underwent classical orthotopic liver transplantation and the other one recipient underwent living-related liver transplantation.No perioperative deaths occurred.All 16 recipients were followed up for 122(6~260)months.The 1-, 5-, and 10-year survival rates were 93.8%、85.2%and 75.8%, respectively.Among 10 recipients with corneal K-F ring positive with varying degrees after operation and was disappeared in 2 recipients at 7 and 11 months.Among 5 recipients with neuropsychiatric manifestation, 4 recipients showed ameliorative neuropsychic symptoms with varying degrees after operation and 1 recipient died.All the levels of liver function and serum copper-protien of all recipients recovered obviously in 1 month and the 1-, 5-, and 10-year post-operation.Conclusions:Classical orthotopic liver transplantation and living-related liver transplantation not only effectively improves copper metabolism of patient with WD and relieves their severe neurological manifestation, but also improves their life and prolongs survival, which is worthy of clinical promotion.

Acute abdomen is often a general term for abdominal diseases with acute abdominal pain as the main manifestation. Common clinical acute abdomen includes acute appendicitis, acute cholecystitis, acute cholangitis, acute pancreatitis, gastrointestinal perforation, intestinal obstruction and other diseases, its characteristics are great changes, rapid progress, high misdiagnosis rate, high postoperative complication rate and high mortality rate, accurate diagnosis and early treatment can obtain a good prognosis. With our in-depth understanding of the occurrence and development of acute abdomen diseases and the development of evidence-based medicine, minimally invasive technology plays a pivotal role in the diagnosis and treatment of common acute abdomen. Laparoscopy on diagnosis can clarify disease diagnosis to a large extent. For those who cannot undergo surgery, decompression and drainage under endoscopy provides a diversified plan for treatment decisions. In addition, minimally invasive techniques are also used in etiological treatment and complications. Disease, prevention of recurrence in all aspects, Minimally invasive technology is beneficial to the etiological treatment of biliary pancreatitis, appendicitis and cholangitis, and endoscopic technology is more consistent with the minimally invasive concept in the treatment of complications.

Objective:To explore and optimize the teaching content of clinical case discussion course based on clinical pathophysiology and therapy (CPPT), and to improve the teaching quality of this course.Methods:Self-compiled evaluation form was sent to all the students who participated in this course in 2016-2017 school year, and the teaching satisfaction and teaching characteristics were evaluated. The differences of evaluation results from students with different educational programs or teachers with different seniority were compared, and the correlation between evaluation results and teachers' seniority was analyzed.Results:The students had a high evaluation on the course, but students from different programs had significant different comments on thinking inspiring, speech encouraging, questions guiding, process holding and effective feedback, as well as the self-evaluation of mastery degree. For teachers with different seniority, there were significant differences in scores in all aspects except speech encouraging, but no differences in mastery degree. Spearman analysis showed that there was a certain correlation between scores and teachers' seniority.Conclusion:The overall situation of the CPPT case discussion course in our school is worthy of recognition, but it needs to be improved in many aspects.

This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential. Importantly, we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser
A549 Cells ; Animals ; Cell Movement ; Epithelial-Mesenchymal Transition/genetics* ; Focal Adhesion Kinase 1/metabolism* ; Humans ; Lung Neoplasms/pathology* ; MAP Kinase Signaling System ; Mice ; Mitogen-Activated Protein Kinase 7/metabolism* ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/metabolism*

Objective To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors. Methods A case?control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non?complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications. Results Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non?surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6 ± 12.6) days vs. (14.2 ± 6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960?8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862?29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357?21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214?12.658, P<0.001) were the independent risk factors of postoperative complications. Conclusions Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.

Objective To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors. Methods A case?control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non?complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications. Results Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non?surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6 ± 12.6) days vs. (14.2 ± 6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960?8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862?29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357?21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214?12.658, P<0.001) were the independent risk factors of postoperative complications. Conclusions Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.

Thyroid tumors are one of the most common diseases, and the thyroidectomy surgery increases. The outpatient surgery is the new trend in clinic. Is it suited for the thyroidectomy? In this article, we will analyse the setting of hospital, surgeon, surgery, patients, and so on, to prove the safety for the outpatient thyroidectomy. After the analysis, the safety of outpatient thyroidectomy surgery will be ensured only if strictly controlling the condition of hospital, surgeons and patients, and following the relation indications.