ObjectiveTo carry out the clinical comprehensive evaluation of Biantong capsules and Biantong tablets in the treatment of constipation guided by the clinical value of drugs， and to provide a scientific basis for the rational pricing， rational use， and cataloging of Biantong capsules/tablets. MethodThe available evidence and survey data were used for the clinical comprehensive evaluation of Biantong capsules/tablets and three control drugs in the treatment of constipation in terms of the six dimensions including effectiveness， safety， economics， innovation， suitability， and accessibility. ResultIn terms of effectiveness， Biantong capsules/tablets can improve the response rate， with clear pharmacological mechanism. In terms of safety， the absence of toxic reaction， the mild adverse reactions， and the favorable prognosis indicate high safety. In terms of economics， the average daily cost of Biantong capsules/tablets is the lowest among the tested drugs， which indicates a cost-effectiveness advantage. In terms of innovation， Biantong capsules/tablets have been authorized patents in China and listed as members in the third category of new drugs of traditional Chinese medicine/ninth new drugs of traditional Chinese medicine. In terms of suitability， Biantong capsules/tablets are convenient to store and take and have good suitability in terms of drug technical characteristics and drug usage. In terms of accessibility， Biantong capsules/tablets have a wide coverage in hospitals， sufficient capacity， low patient burden， extensive drug catalogue coverage， and no major environmental risk for long-term application. The comprehensive values of the tested drugs follow a descending order of control drug B （84.27 score）， Biantong capsules/tablets （82.47 score）， control drug A （70.47 score）， and control drug C （59.46 score）. The recommendations of the expert panel are Class A （18/18）， which can be directly converted into decision-making. ConclusionBiantong capsules/tablets demonstrate a high clinical comprehensive value in the treatment of constipation， providing a reference for the rational pricing， rational use， and cataloging of drugs.

Objective To systematically review the present status of oral Chinese patent medicines(CPMs)for treating functional dyspepsia(FD),explore the formation rules of CPMs,and reveal the potential problems by referring to the methods and procedures of Scoping review.Methods First,we screened all CPMs from the domestic-related drug catalogs which are generally accepted and own the force of law,then we sorted the CPMs based on the drug instructions while carrying out Chinese and English database document retrieval to review the clinical studies.Descriptive analysis of the basic feature and clinical research evidence of CPMs was performed combined with visual charts.Results This study included 42 CPMs for treating FD.Among the formulas of CPMs,Tangerine peel,Radices saussureae,Poria cocos,Glycyrrhiza,Atractylodes macrocephala,and Six Divine Qu appeared frequently.In addition,96 studies involving 21 CPMs were included,among which Zhizhu Kuanzhong Capsule,Liuwei Anxiao capsule,and Dalitong granules had more clinical literature.By analyzing the included 96 clinical studies,we found that the combination of Chinese and Western medicine was the main intervention,and the effective rate,clinical symptom score,and adverse reactions were the main outcomes that were concerned.In addition,8 studies had off-label use of diseases,involving the Wuling capsule to treat the FD whether the disease was accompanied by depression and anxiety symptoms or not,and Zhizhu Kuanzhong Capsule to treat the FD with anxiety and depression.Although the Wuling capsule and Zhizhu Kuanzhong capsule were off-label used in clinical practice,there was no beyond the scope of the guideline.Conclusion The qi-regulating drug,spleen-strengthening drug and digestant drugs are the usual Chinese medicines used for treating adult FD.In recent years,research on CPMs for treating adult FD has increased rapidly.But there is insufficient reflection of CPMs treatment characteristics,ambiguous differences from the primary and secondary outcomes,multiple composite outcomes,and not explicit information on FD or its symptoms in drug package insert,which needs to be improved in the future.

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Objective:To discuss the feasibility and safety of modified side overlap with fundoplication by Yamashita (mSOFY) in laparoscopic proximal gastrectomy.Methods:Using the method of descriptive case series study, the clinical data of 9 patients with upper gastric cancer who successfully performed mSOFY anastomosis from March 2022 to October 2022 in the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University were retrospectively analyzed.The reconstruction steps of mSOFY anastomosis are as follows: (1) Make a small incision on the right side of the esophageal stump and in front of the anterior wall of the gastric stump; (2) The 45mm linear cutting stapler is placed into the preset anastomosis of the esophagus and the remnant stomach, and the esophagus is rotated 90° counterclockwise along the axis, so that the right wall of the esophagus is anastomosed with the remnant stomach, and the stomach wall is sutured to the left side of the esophagus; (3) The common opening of esophagus and remnant stomach was sutured with inverted suture; (4)Suture the left and lower sides of the esophagus with the remnant stomach to make the esophagus flat against the stomach wall; (5) Open the sutured common opening: due to the pressure of the false dome, the posterior wall of the lower esophageal segment was compressed into a valve-like structure. We mainly observing the postoperative reflux and nutritional improvement of the patients, and recording the intraoperative situation and postoperative complications.Results:Nine patients with upper gastric cancer who completed laparoscopic proximal gastrectomy (mSOFY anastomosis) did not have conversion to laparotomy or intraoperative / postoperative complications. The operation time was (169.4±10.4) minutes, the anastomotic reconstruction time was (51.7±7.1) minutes, the intraoperative bleeding volume was (98.9±43.4) ml, and the number of lymph nodes dissected was (27.2±6.7). The patient recovered well after operation, without any complaints related to reflux esophagitis. Postoperative gastrointestinal radiography showed that the anastomosis was smooth, without stenosis and leakage. The serum albumin [(41.6±3.4) L vs. (39.9±2.6) L], prealbumin [(211.3±38.6) mg/L vs. (205.3±36.0) mg/L], and hemoglobin levels [(126.7±13.2) g/L vs. (121.0±9.7) g/L] of patients before and one month after surgery have no statistically significant differences (all P>0.05). Conclusion:mSOFY anastomosis can be used as one of the safe and feasible reconstruction methods in laparoscopic proximal gastrectomy.

Objective:To discuss the feasibility and safety of modified side overlap with fundoplication by Yamashita (mSOFY) in laparoscopic proximal gastrectomy.Methods:Using the method of descriptive case series study, the clinical data of 9 patients with upper gastric cancer who successfully performed mSOFY anastomosis from March 2022 to October 2022 in the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University were retrospectively analyzed.The reconstruction steps of mSOFY anastomosis are as follows: (1) Make a small incision on the right side of the esophageal stump and in front of the anterior wall of the gastric stump; (2) The 45mm linear cutting stapler is placed into the preset anastomosis of the esophagus and the remnant stomach, and the esophagus is rotated 90° counterclockwise along the axis, so that the right wall of the esophagus is anastomosed with the remnant stomach, and the stomach wall is sutured to the left side of the esophagus; (3) The common opening of esophagus and remnant stomach was sutured with inverted suture; (4)Suture the left and lower sides of the esophagus with the remnant stomach to make the esophagus flat against the stomach wall; (5) Open the sutured common opening: due to the pressure of the false dome, the posterior wall of the lower esophageal segment was compressed into a valve-like structure. We mainly observing the postoperative reflux and nutritional improvement of the patients, and recording the intraoperative situation and postoperative complications.Results:Nine patients with upper gastric cancer who completed laparoscopic proximal gastrectomy (mSOFY anastomosis) did not have conversion to laparotomy or intraoperative / postoperative complications. The operation time was (169.4±10.4) minutes, the anastomotic reconstruction time was (51.7±7.1) minutes, the intraoperative bleeding volume was (98.9±43.4) ml, and the number of lymph nodes dissected was (27.2±6.7). The patient recovered well after operation, without any complaints related to reflux esophagitis. Postoperative gastrointestinal radiography showed that the anastomosis was smooth, without stenosis and leakage. The serum albumin [(41.6±3.4) L vs. (39.9±2.6) L], prealbumin [(211.3±38.6) mg/L vs. (205.3±36.0) mg/L], and hemoglobin levels [(126.7±13.2) g/L vs. (121.0±9.7) g/L] of patients before and one month after surgery have no statistically significant differences (all P>0.05). Conclusion:mSOFY anastomosis can be used as one of the safe and feasible reconstruction methods in laparoscopic proximal gastrectomy.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.

This study systematically and comprehensively sorted out the application status of Chinese patent medicines for the treatment of constipation in the clinic， to provide scientific evidence for future research directions and clinical drug use in this field. Based on the method of scoping review， the Chinese patent medicines for the treatment of constipation were retrieved from three drug lists to obtain the medicines that needed to be evaluated. A comprehensive and systematic search was carried out on the included studies on the treatment of constipation by Chinese patent medicines through eight Chinese and English databases， and the included studies were integrated and analyzed. The results were displayed in combination with charts. Thirty-four Chinese patent medicines and 118 studies were included in this study. According to the efficacies， Chinese patent medicines were divided into 4 categories， namely eliminating accumulation， purging fire， promoting Qi， and moistening bowels， involving 125 Chinese medicines. The overall attention of constipation research is on the rise. Marenwan （granules or soft capsules） gained the highest attention， with 42 studies， followed by Qirong Runchang oral liquid， with 21 studies， and Biantong tablets （capsules）， with 19 studies. There are 10 studies on Congrong Tongbian oral liquid. Seventeen Chinese patent medicines had no corresponding clinical research. There were 8 study design types， and all drugs were mainly randomized controlled trials except Danggui Longhui pill. Among the intervention types， the comparison between Chinese patent medicines and western medicines was the most. The highest outcome indicators were efficacy， safety evaluation， and main symptoms or scores， and there was a lack of a unified core outcome indicator set. There were few studies on adverse reactions and the economy. Only 11.86% of the studies were funded. Clinically， Chinese patent medicines are widely used in the treatment of constipation， and the amount of related research shows an increasing trend. However， some Chinese patent medicines lack corresponding clinical evidence， and the published research has problems such as unrigorous design， ununified criteria for efficacy evaluation， lack of comprehensive evidence studies， and insufficient funds. It is hoped that more investment will be made in this field in the future， and more attention will be paid to drugs with relatively blank research and constipation syndromes with few treatments. Comprehensive evidence studies such as systematic reviews should be carried out actively. And the study design should be standardized to provide reliable evidence for the treatment of constipation with Chinese patent medicines.

ObjectiveTo evaluate the safety， efficacy， and economy of the four Chinese patent medicines （CPMs）， including Simotang oral liquid， Liuwei Anxiao capsule， Baohe pill， and Jianwei Xiaoshi oral liquid in the treatment of functional dyspepsia （FD） by a rapid health technology assessment （RHTA）， thus providing evidence support for clinical decision making. MethodChina National Knowledge Infrastructure （CNKI）， WanFang Database， VIP Chinese Technology Periodical Database （VIP）， China Biology Medicine disc （CBMdisc）， PubMed， EMBASE， Cochrane Library， and Web of Science were searched by computer from inception to March 2022. After literature screening， data extraction， and quality evaluation， the descriptive analysis of the results combined with visual charts was performed. Nineteen studies were included， involving 18 randomized controlled trials （RCTs） and 1 Meta-analysis. Neither economic studies nor health technology assessment （HTA） reports were retrieved. ResultThe four CPMs were safe and effective in the treatment of FD， but economic research was lacking. Among them， Simotang oral liquid could be used for children with FD and FD caused by qi and food stagnation， liver and spleen disharmony， and liver and spleen stagnation. Liuwei Anxiao capsule could be used for adult patients with FD caused by food stagnation. Baohe pill could be used for the elderly with FD. Jianwei Xiaoshi oral liquid could be used for children with FD caused by spleen and stomach weakness. ConclusionThe four CPMs have their advantages in the treatment of FD. Among them， the clinical universality of Simotang oral liquid is higher. However， the quality of clinical evidence is generally low， and comparative analysis among drug dosage forms is lacking. In the future， it is necessary to improve， apply， and promote RHTA for rapid evidence production while carrying out a more standardized and scientific evidence-based demonstration of the comprehensive clinical efficacy of CPMs.

Objective:To evaluate the impact of metastatic site on the prognosis in patients with metastatic renal cell carcinoma (mRCC), and it′s value for modifying the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria.Methods:The data of 218 patients pathologically diagnosed with mRCC were analyzed retrospectively in West China Hospital from Jan. 2009 to Dec. 2019. Among all patients, 71.6%(156/218) were male, and 89.0% (194/218) underwent nephrectomy. Most of the patients were pathologically diagnosed with renal clear cell carcinoma (176 patients, 80.7%). Lung (137/218, 62.8%) was the most observed metastatic site, following by bone (47/218, 26.1%), lymph node (37/218, 17.0%) and liver (23/218, 10.6%). All patients were classified into favorable (26 patients, 11.9%), intermediate (126 patients, 57.8%) or poor (37 patients, 17.0%) risk group according to IMDC criteria. Endpoints of this study were progression-free survival (PFS), overall survival (OS) and tumor response. The impact of metastatic sites on patients’ prognosis was analyzed, and those that had significant relationship with prognosis were then added into IMDC criteria and a modifying IMDC model was established. Predictive value of this model was further evaluated by calculating concordance index (C-index).Results:In the whole cohort, median PFS and OS were 13.0 and 33.0 months. Survival analysis suggested that patients with bone ( P=0.004), brain ( P=0.042) and liver ( P=0.046) had significantly shorter OS. Thus, patients were divided into two groups: patients with bone/brain/liver metastasis (82 patients, 37.6%) and patients with other metastatic sites (136 patients, 62.4%). Compared with patients with other metastatic sites, those who with bone/brain/liver metastasis had inferior tumor response by TKIs treatment (disease control rate: 51.2% vs. 73.5%, P=0.004). Multivariate analysis suggested that bone/brain/liver metastasis had negative impact on OS (25.0 vs. 47.0 mo, P=0.039). Furthermore, bone/brain/liver metastasis also showed significant relationship with shorter OS in IMDC low (30.0 vs. 62.0 months, P=0.036), intermediate (31.0 vs. 48.0 months, P=0.048) or high (7.0 vs. 18.0 months, P=0.037) risk group, indicating that metastatic site had predictive value for prognosis of mRCC patients. Based on that, bone/brain/liver metastasis were added into the IMDC criteria, and weighting each parameter was weighted according to its coefficient to patients’ OS. Finally, a modified IMDC scoring system were established. C-index of this modified model was 0.669 (0.599 for current IMDC criteria). Conclusions:Bone/brain/liver metastasis in mRCC patients indicated a shorter OS duration. When adding bone/brain/liver metastasis as a predictive parameter for prognosis of mRCC patients into IMDC criteria, the modified IMDC criteria could offer more accurate prediction for patients’ survival.