Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma / 中华外科杂志

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ2 test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.

Prevalence and incidence of heart failure among community in China during a three-year follow-up / 老年心脏病学杂志（英文版）

BACKGROUND@#Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.@*METHODS@#Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up.@*RESULTS@#The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05).@*CONCLUSIONS@#Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Reflection on the regulatory path for online sales of Chinese medicinal materials in the context of live streaming / 中国药房

OBJECTIVE To provide feasible regulatory paths for the online sales supervision of Chinese medicinal materials from the perspective of the characteristics of new online sales and the characteristics of Chinese medicinal materials. METHODS Through the investigation of the sales form of Chinese medicinal materials on the e-commerce platform and the search of Chinese medicinal materials online dispute cases， the difficulties and existing problems in the supervision of Chinese medicinal materials under the new online sales model were analyzed， and corresponding countermeasures were proposed. RESULTS & CONCLUSIONS Clarifying the conceptual boundary between Chinese medicinal materials and their decoction pieces， agricultural products and food is the key to standardizing the online sale of Chinese medicinal materials. The regulatory criteria， which determine whether Chinese medicinal materials belong to drug management based on whether they had been included in medicinal channels， didn’t consider the diversity of online sales channels for Chinese medicinal materials， their safety and the disguised sales of Chinese herbal decoction pieces. It is necessary to establish the concept of hierarchical management of Chinese medicinal materials， strictly restrict the behavior of claiming the efficacy of Chinese medicinal materials and selling Chinese herbal decoction pieces in live streaming， improve the defining path of false propaganda of Chinese medicinal materials， implement the responsibilities and obligations of live streaming marketing subjects and platforms， and safeguard the legitimate rights of consumers.

Clinical features of POEMS syndrome initially diagnosed as pulmonary hypertension / 中华全科医师杂志

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

Value of triglyceride-glucose index combined with obesity index in predicting nonalcoholic fatty liver disease in individuals with obstructive sleep apnea / 临床肝胆病杂志

Objective To investigate the value of triglyceride-glucose index (TyG), TyG combined with body mass index (BMI), and TyG combined with waist circumference (WC) in predicting nonalcoholic fatty liver disease (NAFLD) in patients with obstructive sleep apnea (OSA). Methods A retrospective analysis was performed for 190 patients who underwent sleep respiratory monitoring and were diagnosed with OSA in The Second Affiliated Hospital of Kunming Medical University from January 2020 to December 2021, and according to the results of ultrasonography, they were divided into OSA+NAFLD group with 107 patients and control group with 83 patients. The t -test or the Mann Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The binary logistic regression analysis was used to explore the influencing factors for the development of NAFLD in patients with OSA. The receiver operating characteristic (ROC) curve was plotted for TyG, TyG combined with BMI, and TyG combined with WC in predicting NAFLD in the patients with OSA, and the area under the ROC curve (AUC) was calculated. The Z test was used for comparison of AUC. Results Compared with the control group, the OSA+NAFLD group had significantly higher BMI, neck circumference, WC, apnea-hypopnea index, oxygen desaturation index, alanine aminotransferase, gamma-glutamyltransferase, triglyceride, fasting plasma glucose, and TyG and significantly lower age, average SpO 2 , LSaO 2 , and high-density lipoprotein cholesterol (all P < 0.05). The binary logistic regression analysis showed that TyG (odds ratio [ OR ]=1.961, 95% confidence interval [ CI ]: 1.03-3.73, P =0.04), BMI ( OR =1.203, 95% CI : 1.03-1.41, P =0.020), and WC ( OR =1.074, 95% CI : 1.01-1.14, P =0.026) were independent risk factors for NAFLD in patients with OSA. TyG, TyG combined with BMI, and TyG combined with WC had an AUC of 0.696 (95% CI : 0.625-0.760), 0.787 (95% CI : 0.722-0.843), and 0.803 (95% CI : 0.739-0.857), respectively, in predicting NAFLD in OSA patients, with an optimal cut-off value of 8.72, 0.36, and 0.60, respectively. TyG combined with BMI had a significantly higher value than TyG in predicting NAFLD in OSA patients ( Z =2.542, P =0.011), and TyG combined with WC also had a significantly higher predictive value than TyG ( Z =2.976, P =0.002 9). Conclusion TyG, TyG combined with BMI, and TyG combined with WC have a good value in predicting NAFLD in OSA patients, among which TyG combined with WC has the best predictive value and is thus expected to become a predictor for the risk of NAFLD in OSA patients.

Long-term intermittent fasting induces abnormal lipid accumulation in mouse liver / 生理学报

Short-term intermittent fasting (IF) is beneficial to weight control in patients with nonalcoholic fatty liver disease, but the impact of long-term IF is not clear. In this study, healthy C57BL/6N mice with 4-month alternate day fasting (ADF) were used to study the effects of long-term IF on systemic and liver lipid metabolism. The results showed that, compared with the Ad Libitum group, the weight and food conversion rate of mice in the ADF group were markedly decreased and increased respectively, and the liver index and the liver content of triglyceride were significantly increased by pathological examination. qRT-PCR analysis revealed that the mRNA expression of the lipogenesis gene Pparγ and lipolysis gene Atgl was up-regulated in the ADF group (P < 0.05). Western blot analysis showed that the ratio of microtubule associated protein LC3-II/LC3-I was increased, while the abundance of autophagy adaptor protein p62 was decreased in the ADF group. In addition, autophagy signal positive regulation key factor AMPK phosphorylation was increased (P < 0.05), and negative regulation factor mTOR phosphorylation was decreased (P < 0.05) in the ADF group, indicating that hepatocyte autophagy activity was elevated. Taken together, ADF for 4 months results in an excessive liver triglyceride accumulation, accompanied by a marked decrease in liver mTOR phosphorylation and a significant increase in hepatic autophagy.

The ineffective or short-term recurrence of trigeminal neuralgia after microballoon compression:different causes and management strategies / 中华外科杂志

Objectives: To explore the causes of ineffective or short-term recurrence (within 3 months)of trigeminal neuralgia treated by percutaneous microballoon compression(PBC), and to examine the reoperative strategies and clincal outcomes of modified PBC. Methods: The clinical data of 21 patients with ineffective or short-term recurrence after PBC treatment (5.7% of 369 patient received PBC) admitted to the Department of Neurosurgery,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University from June 2018 to June 2020 were retrospectively analyzed.There were 8 males and 13 females, mean aged 66.6 years (range:51 to 79 years).Among them,2 patients was ineffective after PBC and 19 patients relapsed within 3 months.The distribution of pain was along V2 branches in 2 cases,V3 branches in 3 cases,V1+V2 branches in 1 case,and V2+V3 branches in 15 cases.The mean time of recurrence was 46.8 days (range:23 to 76 days) among the 19 patients with short-term recurrence.The patients were divided into 4 types based on the causes of postoperative ineffectiveness or short-term recurrence.TypeⅠ:extracapsular false pear (1 case);Type Ⅱ:invalid true pear(2 cases);Type Ⅲ:capsular rupture (6 cases);Type Ⅳ:compression blind area (12 cases).The individualized modified PBC operation plans were used according to the types of the patients and the clinical effect and complications of the patients were observed. Results: The pain symptoms of the patients disappeared after the second operation with immediate effective rate of 100%. All patients had mild facial numbness after surgery.Five patients(23.8%,5/21) had masseter muscle weakness, 3 (14.3%,3/21) had peristomatous herpes, 1(4.8%, 1/21) had diplopia.No bleeding or other complications occurred.All patients were followed up for at least 12 months (range:13 to 28 months). One patient (4.8%,1/21) (compression blind area type) had pain recurrence 9 months after surgery, and cured by receiving the original modified PBC surgery again with no recurrence after another 13 months' follow-up. None of the other patients relapsed during the follow-up period.Up to the last follow-up,19 cases(90.5%,19/21) were cured,and 2 cases (9.5%,2/21) were relieved. Conclusions: The main reason for ineffective or short-term recurrence of PBC in trigeminal neuralgia patients is the ineffectively compressed of trigeminal ganglion.According to the different types of patients,the use of individualized modified surgical scheme can improve the efficacy of PBC surgery.

Comparison of distal pancreatectomy with celiac axis resection and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer / 中华外科杂志

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ2 test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ2=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ2=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.

Comparative clinical efficacy analysis of pancreatoduodenectomy for distal bile duct and pancreatic head cancer: a report of 1 005 cases / 中华外科杂志

Objective: To compare and analyze the clinical efficacy of pancreaticoduodenectomy for distal bile duct cancer and pancreatic head cancer. Methods: Clinical data of 1 005 patients who underwent pancreaticoduodenectomy and postoperative pathological examination confirmed the diagnosis of distal bile duct cancer and pancreatic head cancer at the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were analyzed retrospectively. There were 112 cases in the distal bile duct cancer group, 71 males and 41 females,with age (M(IQR)) of 65(15) years(range: 40 to 87 years); 893 cases in the pancreatic head cancer group, 534 males and 359 females,with age of 64(13)years(range: 16 to 91 years). The differences between clinicopathological characteristics and postoperative overall survival of the two groups were analyzed by χ2 test, Fisher's exact probability method, rank sum test or log-rank test, respectively. The difference in postoperative overall survival between the two groups was compared using Kaplan-Meier method after propensity score matching (1∶1). Results: Compared with the pancreatic head cancer group,the distal bile duct cancer group had shorter operative time (240.0(134.0) minutes vs. 261.0(97.0) minutes, Z=2.712, P=0.007),less proportion of combined venous resection (4.5% (5/112) vs. 19.4% (173/893), χ²=15.177,P<0.01),smaller tumor diameter (2.0(1.0) cm vs. 3.0(1.5) cm,Z=10.567,P<0.01),higher well/moderate differentiation ratio (51.4% (56/112) vs. 38.0% (337/893), χ²=7.328, P=0.007),fewer positive lymph nodes (0(1) vs. 1(3), Z=5.824, P<0.01),and higher R0 resection rate (77.7% (87/112) vs. 38.3%(342/893), χ²=64.399, P<0.01),but with a higher incidence of overall postoperative complications (50.0% (56/112) vs. 36.3% (324/892), χ²=7.913,P=0.005),postoperative pancreatic fistula (28.6% (32/112) vs. 13.9% (124/893), χ²=16.318,P<0.01),and postoperative abdominal infection (21.4% (24/112) vs. 8.6% (77/892), χ²=18.001,P<0.01). After propensity score matching, there was no statistical difference in postoperative overall survival time between patients in the distal bile duct cancer group and the pancreatic head cancer group (50.6 months vs. 35.1 months,Z=1.640,P=0.201),and multifactorial analysis showed that tumor site was not an independent risk factor affecting the prognosis of patients in both groups after matching (HR=0.73,95%CI:0.43 to 1.23,P=0.238). Conclusions: Patients with distal bile duct cancer are more likely to benefit from early diagnosis and surgical treatment than patients with pancreatic head cancer,but with a relative higher postoperative complication rates. The different tumor origin site is not an independent risk factor for prognosis of patients with distal bile duct cancer and pancreatic head cancer after propensity score matching.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Economic evaluation of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma （MPM）. METHODS From the perspective of healthcare system ，a partitioned survival model were developed ，the cost-effectiveness of nivolumab combined with ipilimumab （dual-immunotherapy plan ）versus chemotherapy in the first-line treatment of unresectable MPM by cost-utility analysis. Clinical trial data were collected from CheckMate 743 study. Direct medical cost included drug costs ，disease management cost and cost of treatment of adverse reactions. Costs and utilities were discounted at an annual rate of 5％. The willingness to pay threshold was 3 times of gross domestic product （GDP）per capita in 2021 [242 928 yuan/QALY（quality-adjusted life year ）]. Scenario analysis was used to analyze and compare the two regimens under the scenario of complimentary drug for patients in dual-immunotherapy group. The robustness of the findings was evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS Baseline analysis results showed that total cost of dual-immunotherapy regimen was higher than that of chemotherapy regimen ，and the utility was also better than that of chemotherapy plan ；the incremental cost-effectiveness ratio （ICER）was 417 122.2 yuan/QALY，which was higher than the willingness to pay threshold ；the dual-immunotherapy regimen was not cost-effective compared to the chemotherapy regimen. Under the scenario of complimentary drug ，the cost of dual-immunotherapy was 327 454.5 yuan，ICER was 75 664.1 yuan/QALY，which was lower than the willingness to pay threshold and resulted in a reversal of the baseline analysis. One-way sensitivity analysis showed that under the health states of progression free survival and progressive disease ，utility value and the price of nivolumab had a greater impact on the ICER value. Probabilistic sensitivity analysis showed that the results of baseline analysis were robust. CONCLUSIONS At a 163.com willingness to pay threshold of 3 times of GDP per capita in nivolumab combined with ipilimumab is not cost-effective compared with chemotherapy regimen in the first-line treatment of unresectable MPM. However ，if patients receive complimentary drugs ，the dual-immunotherapy regimen is cost-effective.

CHINA PH ARMACY Volume 33，Number 16，August 30，2022 Semimonthly Table of Contents Analysis of trans-provincia l distribution supervisio n of TCM decoction pieces in accordance with provincial standards from the perspective of benefit and risk / 中国药房

OBJECTIVE To provide ideas for solving the dispute of trans-provincial distribution of traditional Chinese medicine （TCM） decoction pieces in accordance with provincial standards （hereinafter referred to as “local TCM decoction pieces”）. METHODS Through simulation scenarios and collecting actual cases ，the conditions of trans-provincial distribution of local TCM decoction pieces were listed ；the official websites were searched or relevant personnel of drug supervision were interviewed；the current situation of trans-provincial distribution supervision of local TCM decoction pieces in China were sorted out. Based on the stakeholder theory ，the benefits and risks of main stakeholders were discussed to put forward relevant suggestions from the perspective of benefit /risk balance. RESULTS & CONCLUSIONS The conditions of trans-provincial distribution of local TCM decoction pieces in China included enterprises in B province produced TCM decoction pieces according to the A provincial standards，sold and used them in A province ；enterprises in B province produced TCM decoction pieces according to the B provincial standards ，sold and used them in A province ；enterprises in B province produced TCM decoction pieces according to the C provincial standards ，sold and used them in A province. At present ，there are no clear relevant provisions of national laws about trans-provincial distribution supervision of local TCM decoction pieces. Local regulatory opinions mainly come from the reply of the official website of drug regulatory department to online consultation ，and only Shandong ，Shanghai，Liaoning and Jiangxi have issued replies or normative documents. Totally 41.9％，38.7％ and 32.3％ of the provinces respectively allow the trans-provincial distrbution of local TCM decoction pieces in the above 3 conditions；in addition ，32.3％，16.1％ and 22.6％ provinces have unclear regulatory attitudes towards the 3 conditions. The benefits and risks analysis of relevant stakeholders shows that it is more in line with the scientific regulatory concept of benefit/risk balance to conditionally allow trans-provincial distribution of local TCM decoction pieces ，but the regulatory effect depends on the scientificity of the regulatory strategy. It is suggested that the drug regulatory departments clarify the relationship between the national and local standards for TCM decoction pieces and dingrl375@163.com differentiate the varieties of collection ；clear the regulatory requirements for trans-provincial distribution of local TCM decoction pieces by issuing high-level legal d ocuments；enrich regulatory measures and means ，and gradually adjust the requirements of trans-provincial distribution of local TCM decoction pieces .

Comparative study on the management and implementation of continuing education for licensed pharmacists in 31 provinces of China / 中国药房

OBJECTIVE To provide reference for improving the continuing education management for licensed pharmacists in China. METHODS By searching related policies ，notices and documents of continuing education of licensed pharmacists in various provinces in China ，the retrieval time limit was from the implementation of the licensed pharmacist qualification access system in 1994 to December 31，2021. The organizational structure ，implementation status and problems of continuing education management for licensed pharmacists in 31 provinces were analyzed to put forward the suggestions. RESULTS & CONCLUSIONS At present ， the management subjects of continuing education for licensed pharmacists in China at the national level are still unclear ，and the management subjects of continuing education at the local level are mostly provincial drug administration and （licensed）pharmacist association，and some are pharmaceutical societies ，so the management system needs to be straightened out. At present ，most provinces have selected teaching institutions through public bidding ，basically realize the separation of discipline ，but the openness and transparency of selection standards need to be strengthened. In addition ，there are still some problems ，such as teaching content and methods need to be enriched and optimized ，and insufficient funds guarantee in most areas. It is suggested to clarify the division of responsibilities for the continuing education management of licensed pharmacists in China ，improve the management of teaching institutions ，enrich the teaching contents and forms of continuing education of licensed pharmacists ，and ensure the management funds of continuing education of licensed pharmacists.

Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats / 中国结合医学杂志

OBJECTIVE@#To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways.@*METHODS@#Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK].@*RESULTS@#EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist.@*CONCLUSIONS@#EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

Effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain / 中国药房

OBJECTIVE To study the effects of intrathecal injection of resveratrol on sense of pain and OPG/RANK/RANK-L signal pathway in rats with bone cancer pain. METHODS After treatment via intrathecal tube ，the rats were randomly divided into sham operation group ，model group ，resveratrol low-dose ，medium-dose and high-dose groups （0.25，1，2 mg/kg），with 8 rats in each group. Except for sham operation group ，other groups were given Walker 256 breast cancer cell suspension on the right hind limb tibia to induce bone cancer pain model. After 12 days of modeling ，intrathecal administration was performed in resveratrol groups. The model group and sham operation group received the same volume of dimethyl sulfoxide ，10 μL，once a day ，for 5 days. The paw withdrawal mechanical threshold （PWMT）and paw withdrawal thermal latency （PWTL）were measured at 3 d，5 d after administration. The serum levels of tumor necrosis factor α（TNF-α），interleukin 6（IL-6），IL-1β and chemokine ligand 2 （CCL2）were determined after last medication ，and the protein expressions of RANK ，RANK-L and OPG in tibia were also determined. RESULTS Compared with sham operation group ，PWMT and PWTL were significantly decreased in the model group 12 days after operation （P＜0.05）. Compared with model group ，PWMT and PWTL were significantly increased in resveratrol medium-dose and high-dose groups at 3 d and 5 d after administration （P＜0.05）. Compared with model group ，the levels of TNF-α，IL-6，IL-1β and CCL2 in serum were significantly decreased in resveratrol middle-dose and high-dose groups at 5 d after administration（P＜0.05）；the expression of IL- 6 in serum was significantly decreased in resveratrol low-dose group （P＜0.05）； the protein expressions of RANK-L and RANK in tibia were significantly decreased ，while the protein expression of OPG was increased significantly in resveratrol middle-dose group （P＜0.05）. CONCLUSIONS Resveratrol by intrathecal injection can relieve the inflammation caused by bone cancer pain of rats ， the mechanism of which may be associated with inhibiting the activity of OPG/RANK/RANK-L signal pathway.

Enlightenment of Continuing Education Curriculum and Implementation Management System for Licensed Pharmacists in the United States to China / 中国药房

OBJECTIVE：To provide reference f or optimizing the curriculum management system of continuing education for licensed pharmacists in China. METHODS ： The content and implementation system of continuing education curriculum management for licensed pharmacists in the United States was introduced ，and policy suggestions were put forward for the curriculum construction and management system optimization of continuing education for licensed pharmacists in China. RESULTS & CONCLUSIONS ：The curriculum management of continuing education for licensed pharmacists in the United States has clear curriculum objectives ，missions and plans ，and evaluates the basic situation of the trainees before continuing education starts ，so as to carry out modular management of the curriculum （including continuing education courses based on knowledge ，application and practice）. In terms of the implementation system of continuing education in the United States ，ACPE has put forward a lifelong learning model （pharmacist continuing career development model ）that emphasizes autonomy and personalization ，and has detailed regulations on teaching methods ，learning cycle and fees. At the same time ，ACPE requires that the feedback of participants on the curriculum must be collected. Combined with the practice in China ，it is suggested that the relevant departments should formulate the Curriculum Standard of Continuing Education for Licensed Pharmacists ， implement standardized management of the curriculum，improve the assessment mechanism of continuing education curriculum ，flexibly grant credits based on the actual education effect ，constantly update the concept and mode of continuing education ，and localize the international theory ，so as to continuously improve the continuing education management system of licensed pharmacists in China.

Exosomes derived from human-induced pluripotent mesenchymal stem cells inhibit the pyrolysis of alveolar macrophages / 中华危重病急救医学

Objective:To investigate the effect and mechanism of exosomes derived from human-induced pluripotent mesenchymal stem cells (iMSC-Exos) on alveolar macrophages (AM) pyroptosis.Methods:The exosomes in the culture supernatant of human-induced pluripotent mesenchymal stem cells (iMSC) were extracted by rotating ultrafiltration, and the extracted exosomes were identified by transmission electron microscopy, Western blotting and high-resolution adjustable resistance pulse. The rat alveolar macrophage cells (NR8383 cells) were cultured in vitro and the logarithmic growth phase cells were divided into three groups: the control group was added with an equal volume of phosphate buffered saline (PBS) in the AM supernatant; in LPS/ATP group AM cells were stimulated with 500 μg/L LPS for 23 hours and then 5 mmol/L ATP was added for 1 hour to induce pyrolysis; iMSC-Exos group was incubated with AM and 100 mg/L iMSC-Exos for 3 hours before giving LPS and ATP. The cytotoxic activity was detected by cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) analysis, the apoptosis and the expression of caspase-1 were observed by immunofluorescence, the levels of inflammatory factors interleukins (IL-1β and IL-18) released by AM were detected by enzyme linked immunosorbent assay (ELISA), the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and the expression level of pyroptosis related protein gasdermin D (GSDMD) were detected by Western blotting. Results:The extracted exosomes were observed by transmission electron microscopy as round vesicles, expressing exosomal markers CD63 and CD9 showed by Western blotting, high-resolution adjustable resistance pulse showed the average diameter of the particles was 130 nm, and could be uptaken by AM. Compared with the control group, the cell activity decreased [(0.56±0.05)% vs. (1.06±0.07)%, P < 0.01], the release of necrotic substance LDH increased (U/L: 1 218.86±22.73 vs. 188.30±1.61, P < 0.01), the expression levels of inflammatory factors increased [IL-1β (ng/L): 958.91±32.78 vs. 194.63±5.14, IL-18 (ng/L): 870.89±21.86 vs. 288.85±24.48, both P < 0.01], and the apoptosis rate [(55.35±6.19)% vs. (12.01±1.32)%, P < 0.01] and caspase-1 expression (fluorescence intensity: 41.06±3.65 vs. 2.80±0.54, P < 0.01) elevated in the AM after LPS/ATP stimulation, suggesting that LPS combined with ATP successfully induced alveolar pyroptosis. Compared with the LPS/ATP group, AM pretreated with iMSC-Exos showed increased cell viability [(0.81±0.05)% vs. (0.56±0.05)%, P < 0.01], decreased LDH secretion (U/L: 535.05±42.55 vs. 1 218.86±22.73, P < 0.01), decreased expression of inflammatory factors [IL-1β (ng/L): 381.82±19.50 vs. 958.91±32.78, IL-18 (ng/L): 533.77±31.54 vs. 870.89±21.86, both P < 0.01], and decreased apoptosis rate [(19.74±2.96)% vs. (55.35±6.19)%, P < 0.01] and caspase-1 expression (fluorescence intensity: 12.16±1.31 vs. 41.06±3.65, P < 0.01). At the same time, the expression of NLRP3 inflammasome pathway [NLRP3 protein (NLRP3/β-actin): 0.62±0.06 vs. 1.89±0.11; cleaved caspase-1 protein (cleaved caspase-1/β-actin): 0.42±0.07 vs. 1.22±0.17, both P < 0.01] and pyrolysis-related protein was significantly inhibited [GSDMD protein (GSDMD/β-actin): 0.57±0.05 vs. 1.22±0.05, P < 0.01]. Conclusion:iMSC-Exos successfully reversed the AM pyroptosis and inflammatory factor expression induced by LPS/ATP, which may be due to the targeted inhibition of NLRP3 inflammasome pathway, suggesting that iMSC-Exos can exert anti-inflammatory effects by inhibiting the pyrolysis of AM.

Post-marketing Risk Management of Biopharmaceuticals in the United States and Its Enlightenment to China / 中国药房

OBJECTIVE：To learn from the experie nce of post-marketing risk management of biopharmaceuticals in the United States，and to provide reference for post-marketing risk management of biopharmaceuticals in China. METHODS ：By studying guidance documents and website information issued by FDA ，the risk management of biopharmaceuticals after marketing in the United States was analyzed. Taking infliximab as an example ，the specific implementation situation was introduced ，the management characteristics were summarized ，and the enlightenment and relevant suggestions were put forward for the risk management of biopharmaceuticals after marketing in China. RESULTS & CONCLUSIONS ：The post-marketing risk management of biopharmaceuticals in the United States mainly includes two aspects as “risk evaluation and mitigation strategy （REMS）”and “post-marketing study and clinical trials system ”. The latter included post-marketing requirement （PMR） and post-marketing commitment（PMC）. Taking infliximab as an example ，since it was approved by FDA in August 1998，its manufacturer submitted REMS to FDA in 2009 and obtained approval ，and proposed post-marketing studies and clinical trials for five times. It can be seen that FDA has issued specific guidelines for post-marketing risk management of biopharmaceuticals to encourage multi-role participation in risk management ， realize effective communication with patients ， and continuously supervise the risk of biopharmaceuticals，so as to reduce the risk of the use of biopharmaceuticals. For biopharmaceuticals ，China has not yet formulated systematic and specific implementation rules and guidelines ，and there is still lack in post-marketing risk management. It is suggested that China can learn from the measures and system of post-marketing risk management of biopharmaceuticals in the United States ，involve stakeholders in post-marketing management ，enhance patients ’awareness of drug use risks through effective communication，and further improve the post-marketing research management system to guarantee patients ’safety of drug use.

Analysis of the Continuing Education System for Licensed Pharmacists in the UK and Its Enlightenment to China / 中国药房

OBJECTIVE：To provide reference for improving the continuing education system for licensed pharmacists in China by learning from the mature experience of the continuing education system of licensed pharmacists in the UK. METHODS ： Literature research method was adopted to summarize and analyze the organizational structure ，specific contents and implementation methods of the continuing education system for licensed pharmacists in the UK by combing the English and Chinese literatures ， official policies and reports of the continuing education system for licensed pharmacists in the UK. The suggestions and reflections were put forward to improve the continuing education system of licensed pharmacists in China. RESULTS & CONCLUSIONS ：The management organization of continuing education system for licensed pharmacists in the UK is mainly UK Association of Boards of Pharmacy，the organizations of which provide continuing education include pharmacy associations ，pharmaceutical education institutions，pharmaceutical colleges and universities. Continuing education system of licensed pharmacists in the UK is relatively perfect，including personal needs analysis ，systematic continuing education courses ，self-education and evaluation reflection of licensed pharmacists ，forming a systematic circulation system ；continuing education is carried out for pharmacists in different practicing fields ，with equal emphasis on theory and practice. In terms of continuing education ，the UK focuses on face-to-face ， one-to-one training ，and provides many free continuing education courses. Compared with the UK ，the continuing education system of licensed pharmacists in China still has some gaps. For example ，the self-education and self-evaluation awareness of licensed pharmacists is not strong ，the content and form of continuing education lack of pertinence and practicality ，and the re-registration management of pharmacists ’practicing qualifications is more formalistic. It is recommended that licensed pharmacists in China establish the concept of self-education ，strengthen the practicality of continuing education for pharmacists ，carry out refined continuing education for pharmacists in different fields of practice ，and strengthen the management of re-registration of licensed pharmacists，so as to form a systematic and effective circulation system for continuing education of licensed pharmacists in China.

Researches about Motor Imagery-Stroke in Recent Ten Years: A Visual Analysis / 中国康复理论与实践

Results and Conclusion:The mean of articles published was 70.5 a year. Germany, USA, UK were the top countries of cooperative documents; Tübingen University, Keio University and Shanghai Jiao Tong University were the top institutions. The most cooperative articles were involved the team of Gharabaghi A. Motor imagery-brain computer interface, network, motor function, especially walking function, may be the focuses in the future. Objective:To summarize the research structure of motor imagery applied in stroke and identify the hotspots and development. Methods:Literatures about motor imagery applied in stroke collected in Web of Science core database between 2010 to 2020 were obtained, and analyzed with CiteSpace software to draw the relevant knowledge mapping of related countries, institutions, authors, and keywords, etc.