AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

Objective To explore the safety and feasibility of intravenous dexmedetomidine(Dex)combined with targeted infusion of remifentanil in endoscopic retrograde cholangiopancreatography(ERCP)anesthesia in older adult patients.Methods From January to August 2021,98 older adult patients(≥65 years old)undergoing ERCP were randomly divided into TRP and TRD groups.The TRP group was anesthetized with target-controlled infusion of propofol and remifentanil and the TRD group was treated with Dex combined with target-controlled infusion of remifentanil.mean arterial pressure(MAP),heart rate(HR),electrocardiogram(ECG),respiratory rate(RR),pulse oxygen saturation(SpO2),bispectral index(BIS)before anesthesia induction(T0),immediately after induction of anesthesia(T1),endoscopic introduction(T2),duodenal papilla intubation(T3),endoscopy withdrawal(T4)and postoperative awakening(T5)were observed.Arterial blood gas analysis at different time points(T0,every 15 min after anesthesia induction and T5),PaO2,and PaCO2,were recorded at the above mentioned time points;and the remifentanil concentration in target-controlled infusion,operation time,recovery time(from infusion of remifentanil to consciousness recovery),anesthesia recovery time(from consciousness recovery to leaving the operating room),intraoperative body movement,Aldrete scores out of the room,Visual Analogue Scale(VAS)at 60 min after surgery,occurrence of post-operative adverse reactions,as well as the satisfaction of anesthesiologists,endoscopists,and patients were recorded.Results Compared with the TRP group,MAP at T1 and T3,SpO2 and RR at T1,T2,T3,and T4,and BIS at T2,T3,T4,and T5 increased,whereas HR at T1,T2,T3,and T4 decreased;the number of mandibular rests,incidence of hypoxemia,Aldrete score,and satisfaction increased,whereas the VAS score at 60 min after surgery decreased in the TRD group(P<0.05).There were no statistically significant differences in postoperative adverse reactions,PaO2 and PaCO2,target-controlled infusion remifentanil concentration,operation time,recovery time,and anesthesia recovery time between the two groups.Conclusion Compared with the target-controlled infusion of propofol-remifentanil,intravenous infusion of Dex combined with target-controlled infusion of remifentanil can reduce the incidence of hypoxemia in older adult patients during ERCP surgery,and the anesthesia regimen can meet the anesthesia needs of ERCP surgery,which is safe and feasible.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.
Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Nomograms ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms/surgery*

OBJECTIVE: To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma. METHODS: We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups. RESULTS: There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729). CONCLUSION Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Humans ; Immunotherapy/methods* ; Liver Neoplasms/drug therapy* ; Prospective Studies ; Retrospective Studies

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.
Autism Spectrum Disorder/therapy* ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects* ; Feces ; Female ; Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies

Breast Neoplasms/surgery* ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating/surgery* ; China ; Female ; Humans ; Mastectomy

Objective:To compare the short-term efficacy of Billroth Ⅱ+Braun anasto-mosis versus Roux-en-Y anastomosis in totally three-dimensional (3D) laparoscopic distal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 140 patients with gastric cancer who were admitted to the First Medical Center of Chinese PLA General Hospital from January 2016 to January 2020 were collected. There were 105 males and 35 females, aged from 23 to 84 years, with a median age of 55 years. Of the 140 patients, 54 patients undergoing totally 3D laparoscopic distal gastrectomy with Billroth Ⅱ+Braun anastomosis were allocated into Billroth Ⅱ+Braun group, and 86 patients undergoing totally 3D laparoscopic distal gastrectomy with Roux-en-Y anastomosis were allocated into Roux-en-Y group, respectively. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect remnant gastritis and its severity, bile reflux, reflux esophagitis in the postoperative 3 months up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the Mann-Whitney U test. Results:(1) Surgical situations: 140 patients underwent totally 3D laparoscopic distal gastrectomy. The operation time, cases with volume of intraoperative blood loss <50 mL, 50 to 200 mL or >200 mL, the number of lymph node dissected were (233±39)minutes,15, 35, 4, 30±13 for the Billroth Ⅱ +Braun group , respectively, versus (240±52)minutes,25, 51, 10, 27±10 for the Roux-en-Y group, showing no significant difference between the two groups ( t=0.856， χ2=0.774， t=1.518， P>0.05). (2) Postoperative situations: cases with drainage tube, time to postoperative first flatus, cases with postoperative grade Ⅱ, Ⅲ, Ⅳ, Ⅴ complications, cases with postoperative complications, cases with postoperative severe complications, duration of postoperative hospital stay, surgery cost and total hospitalization cost of the Billroth Ⅱ+Braun group were 38, (3.5±0.8)days,4, 1, 0, 0, 5, 1, (9.0±5.0)days, (3.8±1.2)×10 4 yuan and (9.7±2.1)×10 4 yuan, respectively. The above indicators of the Roux-en-Y group were 59, (3.7±1.0)days, 9, 1, 0, 1, 11, 2, (9.0±4.0)days, (4.3±1.0)×10 4 yuan and (9.2±2.1)×10 4 yuan, respectively. There was a significant difference in the surgery cost between the two groups ( t=2.453, P<0.05), while there was no significant difference in cases with drainage tube, time to postoperative first flatus, cases with postoperative grade Ⅱ, Ⅲ, Ⅳ, Ⅴ complications, cases with postoperative complications, duration of postoperative hospital stay or total hospitalization cost between the two groups ( χ2=0.049, t=?1.339, Z=0.000, χ2=0.409, t=0.197, 1.383, P>0.05). There was also no significant difference in cases with postoperative severe complications between the two groups ( P>0.05).(3) Follow-up: 134 of 140 patients received the follow-up, including 52 cases in the Billroth Ⅱ+Braun group and 82 cases in the Roux-en-Y group. Results of follow-up within postoperative 3 months showed that the incidence rates of remnant gastritis, bile reflux, reflux esophagitis were 61.5%(32/52), 38.5%(20/52), 26.9%(14/52) for the Billroth Ⅱ+Braun group, respectively, versus 41.5%(34/82), 22.0%(18/82), 12.2%(10/82) for the Roux-en-Y group, showing significant differences between the two groups ( χ2=5.131, 4.270, 4.695, P<0.05). Cases with grade 0,Ⅰ,Ⅱ, Ⅲ, Ⅳ residual food were 42, 3, 5, 2,0 for the Billroth Ⅱ+Braun group, versus 67, 9, 1, 5,0 for the Roux-en-Y group, showing no significant difference between the two groups ( Z=?0.156, P>0.05). Cases with minimal lesion, grade A, grade B gastritis (severity of gastritis) were 6, 5, 3 for the Billroth Ⅱ+Braun group, versus 8, 2, 0 for the Roux-en-Y group, showing no significant difference between the two groups ( Z=?1.468, P>0.05). Conclusions:It is safe and feasible to operate Billroth Ⅱ+Braun or Roux-en-Y anastomosis in totally 3D laparoscopic distal gastrectomy. Billroth Ⅱ+Braun anastomosis can reduce the surgical cost. Roux-en-Y anastomosis has advantages in reducing the incidence of reflux esophagitis, bile reflux and reflux gastritis.

Objective: At present, there are few studies focusing on the factors short-term complications after total gastrectomy in patients with advanced gastric cancer receiving neoadjuvant chemotherapy (NACT). The purpose of this study is to provide a reference for clinical prevention of complications in these patients. Methods: A retrospective case-control study was conducted. Case inclusion criteria: (1) clinical stage II-III gastric cancer diagnosed by preoperative gastroscopy, pathology, abdominal CT, EUS or PET-CT; (2) evaluated suitable for NACT by MDT discussion; (3) no previous history of other malignant tumors and no concurrent tumor; (4) undergoing total gastrectomy+ D2 lymphadenectomy after NACT. Exclusion criteria: (1) age <18 or >80 years old; (2) severe concurrent diseases, and ASA classification>grade III; (3) stump gastric cancer or history of gastric surgery; (4) incomplete clinicopathological data. According to the above criteria, clinicopathological data of 140 advanced gastric cancer patients who underwent total gastrectomy after NACT in Chinese PLA General Hospital between June 2012 and June 2019 were collected, including 109 males and 31 females with mean age of (56.9±11.4) years and body mass indey (BMI) of (23.3±3.1) kg/m(2). Logistic analysis was used to analyze the relationship between postoperative complication and clinicopathological data. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results: Postoperative complications (Clavien-Dindo classification ≥ II) occurred in 35 cases (25.0%) and severe complications (Clavien-Dindo classification ≥ IIIa) occurred in 4 cases (2.9%), including 1 case of esophago-jejunal anastomotic leakage, 1 case of vena cava thrombosis, 1 case of pleural effusion, 1 case of septic shock during perioperative days resulting in death. Univariate analysis showed that BMI (P=0.011), cycle of NACT (P=0.027), tumor diameter (P=0.021), and vascular invasion (P=0.033) were associated with postoperative complication within 30 days, while open/laparoscopic total gastrectomy were not associated with postoperative complication (P=0.926). Multivariate analysis revealed that BMI ≥ 25 kg/m(2) (OR=3.294, 95% CI: 1.343-8.079, P=0.009) and < 4 cycles of NACT (OR=2.922, 95% CI: 1.217-7.016, P=0.016) were independent risk factors for postoperative complication. The 3-year overall survival rates of patients with or without complication were 54.4% and 64.0%, respectively (P=0.395), and 3-year disease-free survival rates were 47.4% and 52.9%, respectively (P=0.587). Conclusions: Higher BMI and fewer cycles of NACT are independent risk factors of postoperative complication in advanced gastric cancer patients undergoing total gastrectomy after NACT. No obvious association is found between postoperative complication and surgical approaches.
Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Gastrectomy/adverse effects* ; Humans ; Lymph Node Excision ; Male ; Middle Aged ; Neoadjuvant Therapy ; Postoperative Complications/etiology* ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms/surgery*

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence