Under the new situation of establishing the new standard system for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and promulgating the appendix on pharmaceutical packaging ma-terials in the Good Manufacturing Practice for Drugs,it is urgently necessary to introduce relevant standards for quality agreements on pharmaceutical packaging materials.This article focuses on analyzing the development of group standards for pharmaceutical packaging materials under the new situation,the role and significance of quality agreements for pharmaceutical packaging materials,as well as the interpretation of key parts of the"Guidelines for the Management of Quality Agreements for Pharmaceutical Packaging Materials",in order to help enterprises quick-ly shift from the original"standard-only"approach to strengthening the quality management of the entire product life cycle through quality agreements.

Under the new situation of establishing the new standard system for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and promulgating the appendix on pharmaceutical packaging ma-terials in the Good Manufacturing Practice for Drugs,it is urgently necessary to introduce relevant standards for quality agreements on pharmaceutical packaging materials.This article focuses on analyzing the development of group standards for pharmaceutical packaging materials under the new situation,the role and significance of quality agreements for pharmaceutical packaging materials,as well as the interpretation of key parts of the"Guidelines for the Management of Quality Agreements for Pharmaceutical Packaging Materials",in order to help enterprises quick-ly shift from the original"standard-only"approach to strengthening the quality management of the entire product life cycle through quality agreements.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the efficacy and safety of a new China-made direct visualization system of peroral cholangiopancreatography in the diagnosis and treatment of biliopancreatic diseases.Methods:Clinical data of 37 patients who underwent endoscopic examination through the direct visualization system of peroral cholangiopancreatography at Digestive Endoscopy Center of Nanjing Drum Tower Hospital from April 2020 to June 2021 were retrospectively analyzed. Technical success rate and complications were analyzed.Results:The examination was completed in 37 patients through the system. The technical success rate was 100.0%. The nature of biliary stricture was confirmed in 24 cases, presenece or absence of bleeding or residual stones in the bile duct was confirmed in 6 cases, neoplasm or residual stones in the pancreatic duct was determined in 2 cases, biliary stricture was passed assisted with visualized guidewire in 2 cases, and lithotripsy was performed assisted with biliary laser in 3 cases. Nine patients were pathologically diagnosed as having malignant biliary stricture, and 8 of them were confirmed malignant by the system. Drainage was performed in 34 cases after the examination. There were 3 cases of cholangitis, 4 cases of bacteremia and 2 cases of postoperative pancreatitis after the operation, which were relieved in a short time after conservative treatment. Bleeding occurred in 1 case which was improved after two times of endoscopic hemostasis.Conclusion:The new direct visualization system of peroral cholangiopancreatography is safe and effective in the diagnosis and treatment of biliopancreatic diseases.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective: To evaluate the indication, safety and effectiveness of transoral robotic surgery (TORS) for oropharyngeal cancer based on our preliminary experience. Methods: Twelve patients, including six with tonsil cancer, five with tongue base cancer and one with posterior pharyngeal wall cancer, who underwent TORS with Da Vinci Si surgical system from March 2017 to October 2018 at Tongji Hospital of Huazhong University of Science Technology were respectively analyzed. And the surgical time, intraoperative blood loss, postoperative local bleeding, dyspnea, nerve function injury, oral intake time, whether or not to receive chemoradiotherapy were analyzed. Results: All tumors in the 12 patients were en bloc removed by TORS. Surgical time ranged from 25 to 80 min with an average of 34.2 min. The blood loss ranged from 10 ml to 50 ml with an average of 20.8 ml. The recovery time for oral intake ranged from 1 day to 30 days with an average of 8.4 days. No patient underwent tracheostomy after TORS. Also, no patient manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All 12 patients reached pathologically negative surgical margins. The patients were followed up for 4 to 22 months, with a median of 12 months. All patients who combined with more advanced than T3 stage, or more advanced than N2 stage were recommended to oncologist, then, followed with radiotherapy or chemoradiotherapy if no relevant contradictions occurred. No local recurrence or distant metastasis case was found. Conclusion With proper indications, the application of TORS in oropharyngeal cancer is a relatively safe, effective and minimal invasive therapy, which merits more clinical applications.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

This paper reviewed the research progress on pathogenesis and evaluation of dysphagia, swallowing training, and all kinds of swallowing standards among patients after laryngectomy so as to provide a reference and basis for the development of swallowing rehabilitation nursing standard in patients after laryngectomy.

Objective To investigate the long-term efficacy of pure transanal total mesorectal excision (PtaTME) for middle-low rectal cancer.Methods The retrospective descriptive study was conducted.The clinicopathological data of 18 patients with middle-low rectal cancer who were admitted to the Sixth Affiliated Hospital of Sun Yat-sen University from July 2014 to August 2016 were collected.There were 7 males and 11 females,aged (58±13) years,with a range from 40 to 84 years.The body mass index was (22±3) kg/m2.All the 18 patients underwent PtaTME.Observation indicators:(1) surgical and postoperative conditions;(2) postoperative pathological examination;(3) follow-up and survival.Follow-up using inpatient reexamination,outpatient examination,and telephone interview were performed to detect anastomotic complications,anal function,urinary retention,sexual dysfunction,survival and tumor recurrence and metastasis once every 3 months within postoperative 6 months,once every 6 months from 6 months to 3 years,and once a year after 3 years up to June 2019.The measurement data with normal distribution were represented as Mean±SD,and the measurement data with skewed distribution were represented as M (range).Count data were expressed as percentages.Survival rates were calculated by the Kaplan-Meier method.Results (1) Surgical and postoperative conditions:18 patients successfully underwent PtaTME,without conversion to open surgery.The operation time,volume of intraoperative blood loss,distance between anastomosis and anal verge,time to first flatus,time to urinary catheter removal,and duration of postoperative hospital stay were (202±68) minutes,50 mL (range,20-400 mL),(4.5± 2.0)cm,2 days (range,2-7 days),3 days (range,2-5 days),and 7 days (range,5-10 days) in the 18 patients,respectively.There was no perioperative complication.Among 18 patients,4 underwent preventive ileostomy.(2) Postoperative pathological examinations:the length of surgical specimens,the number of lymph node dissection,distance from tumor to the distal margin were (11.0±3.0)cm,12±6,and 1.0 cm (range,0.8-3.7 cm),respectively.The 18 patients had complete mesorectal membrane excision,with negative proximal margin,distal margin,and circumferential margin.Tumor pathological staging:there were 2 cases in Tis stage,4 in T1 stage,7 in T2 stage,and 5 in T3 stage;16 in N0 stage,1 in N1 stage,and 1 in N2 stage.Tumor histological classification:2 patients had carcinoma in situ,9 had moderately differentiated adenocarcinoma,and 7 had high-differentiated adenocarcinoma.(3) Follow-up and survival:18 patients were followed up for 34.0-59.0 months,with a median follow-up time of 57.5 months.During the follow-up,4 patients developed grade B anastomotic leakage and were cured after conservative treatment.One patient developed anastomotic recurrence at 2 years after surgery,and no recurrence was found after surgical resection of the recurrent lesion.Four patients with prophylactic ileostomy had the stoma closured,and the anus function was satisfactory after surgery.There was no urinary retention or sexual dysfunction in the 18 patients.Of the 18 patients,17 had tumor free survival after surgery.The 3-year disease-free survival rate was 94.4％,and the 3-year overall survival rate was 100.0％ in 18 patients.Conclusion PtaTME can achieve high quality of specimen,which is safe and feasible for the treatment of rectal cancer.

Objective To compare the clinical efficacies of transanal total mesorectal excision(TaTME) and laparoscopic total mesorectal excision (LapTME)for rectal cancer (RC).Methods The case-control matching method and retrospective cohort study were conducted.The clinicopathological data of 100 RC patients who were admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between July 2014 and January 2016 were collected.Of 100 patients,50 undergoing TaTME and 50 undergoing LapTME were respectively allocated into the TaTME and LapTME groups by case-control matching method.Observation indicators:(1) operation situations:operation time,volume of intraoperative blood loss,cases with intraoperative complications and preventive stoma;(2) postoperative recovery:time for diet intake,time for out-of-bed activity,occurrence of complications within 30 days postoperatively and duration of hospital stay;(3) postoperative pathological examinations:postoperative pathological specimen length,number of lymph node harvest,distance from lower boundary of tumor to distant margin and cases with positive circumferential margin;(4) follow-up.Follow-up using outpatient examination and network tracing was performed to detect local tumor recurrence and distant metastasis up to December 2016.Measurement data with normal distribution were represented as x±s and comparison between groups was analyzed using the paired-samples t test.Measurement data with skewed distribution were represented as M (range).Comparisons of count data were analyzed using the chi-square test.Comparisons of measurement data with skewed distribution and ranked data were done by the nonparametric test.Results (1) Operation situations:operation time,volume of intraoperative blood loss,cases with intraoperative complications and preventive stoma were (259±111)minutes,100 mL (range,20-2 000 mL),2,28 in the TaTME group and (220± 80)minutes,50 mL (range,20-1 000 mL),1,33 in the LapTME group,respectively,with no statistically significant difference (t=1.90,Z=-0.30,x2 =0.34,0.01,P＞0.05).(2) Postoperative recovery:time for diet intake and time for out-of-bed activity were (1.6±0.5) days,(2.6±0.6) days in the TaTME group and (2.4±0.5)days,(3.5 ±0.6)days in the LapTME group,respectively,with statistically significant differences (t =8.90,11.30,P＜0.05).Cases with anastomotic fistula,bleeding and stenosis,intestinal obstruction,abdominal abscess and wound infection within 30 days postoperatively were 6,1,1,0,1,0 in the TaTME group and 5,1,2,2,1,2 in the LapTME group,respectively,with no statistically significant difference (x2=0.10,0.00,0.30,2.00,0.00,2.00,P＞0.05).Cases with urinary retention within 30 days postoperatively were 3 and 0 in the TaTME and LapTME groups,respectively,with a statistically significant difference (x2 =3.00,P＜0.05).Two and 2 patients with anastomic fistula underwent reoperation in the TaTME and LapTME groups respectively,and other patients were improved by symptomatic treatment.Duration of hospital stay was 7 days (range,5-36 days)and 8 days (range,6-29 days) in the TaTME and LapTME groups,respectively,with no statistically significant difference (Z =-0.90,P ＞ 0.05).(3) Postoperative pathological examinations:postoperative pathological specimen length,number of lymph node harvest,distance from lower boundary of tumor to distant margin and cases with positive circumferential margin were (11±3)cm,13±5,(1.3±0.7)cm,0 in the TaTME group and (12±3) cm,13±5,(1.3±0.7)cm,1 in the LapTME group,respectively,with no statistically significant difference (t=0.50,0.20,0.10,x2=1.00,P＞0.05).(4) Follow-up:100 patients were followed up for 9-27 months,with an average time of 18 months.During the follow-up,distant metastasis and local tumor recurrence were detected in 2,3 patients of TaTME group and in 2,2 patients of LapTME group,respectively,with no statistically significant difference (x2 =0.00,0.20,P＞0.05).Conclusions TaTME for RC is safe and feasible.Compared with LapTME,TaTME not only achieves identical pathological quality without increasing intra-and postoperative complications,but also benefits postoperative recovery of patients.