Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

Aim To study the potential molecular anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology methods,molecular docking technology and cell experiment. Methods The active ingredients targets and disease targets of Aconitum tanguticum were collected through literature and database. The common targets were utilized by mixture of them and the core targets were obtained by constructing the protein protein interaction(PPI)network. Then the component-target-disease network diagram was constructed. The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed for common targets. AutoDock Vina(1.1.2)software was utilized for combining some of the core targets and the diterpenoid alkaloids in the chemical components of Aconitum tanguticum. Finally,the influence of alcoholic extract of Aconitum tanguticum(ATS)on RAW264.7 cell inflammation model was preliminarily verified by MTT assay,Griess reagent and realtime RT-PCR. Results A total 17 main active ingredients were obtained from literature and 284 common targets were obtained via intersecting with disease targets. Altogether 108 pathways were screened by KEGG enrichment,mainly including PI3K-Akt,Ras,MAPK and HIF-1. Molecular docking results indicated that the active ingredients of Aconitum tanguticum had a high affinity with the core target to be docked. In vitro experiment suggested that ATS treatment inhibited LPS-induced NO production and iNOS mRNA in RAW264.7 cells. Realtime RT-PCR detection suggested that ATS played an anti-inflammatory effect by regulating the PI3K-Akt signaling pathway. Conclusions Aconitum tanguticum exerts anti-inflammatory effects through PI3K-Akt pathways,which provides the scientific basis for better promoting the development of Aconitum tanguticum.

Objective To explore and understand limitations and needs of support for conducting clinical research among clinicians in China.Methods The in-service clinician in our hospital were enrolled in as survey participants,survey questionnaires were designed and filled up by target audience in the questionnaire star platform.Results Main problems identified as restrictions for conducting clinical studies including lack of data platform,have ideas but not protocols,lack of research funding and project management.On the other hand,identified needs for support including research-related technical support,project management facilitation,training,external communication and exchange,as well as quality risk management.Conclusions Hospital should establish Clinical Research Unit to help clinicians to improve research quality by training,providing technical support and administrative service of clinical research.

Objective:To construct assessment and evaluation system of clinical research and its application in practice. To explore the reliability, validity and discrimination of this index system, and evaluate its effect.Methods:The cluster was randomly sampled from 54 clinical departments. Taking the department as units, all individuals in each department was conducted a questionnaire survey for empirical analysis. Cronbach's coefficient and factor analysis were used to verify the reliability and validity of the index system. The correlation coefficient method was used to analyze the discrimination. The t-test method was used to calculate the discrimination. Extreme grouping method was used to compare the difference between high grouping and low grouping to validate the difference of each index.Results:Cronbach′s α of the whole index system is 0.840. Through exploratory factor analysis, four common factors were extracted, and the cumulative contribution rate is 56.278%. Through correlation coefficient method and t-test method, results show that except for the " concluding situation" , " number of visitors to clinical scientists workstation" and " personnel selected into talent category clinical research program" , the differences of other indicators were statistically significant ( P<0.05), and the distinguish index was between 0.31 and 0.64. Conclusions:The clinical research assessment system has good reliability and validity. And the discrimination is good. The index system can accurately assess the clinical research situation. It can be used for reference in assessment of clinical efficiency.

Objective To summarize the practical experiences of Clinical Research Unit (CRU) platform established by Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine,provide reference for domestic institutions that have prepared or to prepare to establish CRU platform.Methods Oriented by demand,this platform has set up six modules including project management module,methodology support module,data management module,quality risk management module,project transformation module and training and international exchange module.Besides,it also establishes and improves the corresponding module system,quality assurance,technical support and information data platform system.Results With this platform,the enthusiasm of departments to carry out clinical research has been continuously enhanced,the talent pool of clinical research has been expanded;the awareness of clinical research cooperation has been improved and the international cooperation fields have been further extended;the number of clinical research projects and funding have increased rapidly.Conclusions CRU Platform in Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine provides all-dimensional technical support and whole-process informatization management to improve clinical research quality and efficiency.While learning from the advanced international concepts,we still need to explore and improve the platform construction and management mode in line with general research-oriented hospitals in China,further to enhance the academic research internationally.

Objective To investigate the quantitative value of the signal intensity ratio of extraocular muscle and ipsilateral white matter measured by MRI for the evaluation of activity in thyroid-associated ophthalmopathy. Methods A total of 129 patients and 245 eyeballs with thyroid-associated ophthalmopathy were enrolled in this study and this 245 eyeballs were set as thyroid-associated ophthalmopathy group(TAO group). There were 10 patients with newly diagnosed Graves'disease and in the same period and these 20 eyeballs were set as graves'disease group(GD group). 32 normal people from annual physical test excluded thyroid and eye diseases and their 64 eyes were selected randomly for the normal control group(NC group). The signal intensity of the extraocular muscle and the ipsilateral white matter on the MRI images were measured, while did exophthalmos and the width of the inner fat of eyeballs (FWs)measurements in the same time. Results SIR,FWs,and exophthalmos of TAO group were higher than those of the other 2 groups[SIRs:1.71(1.40,2.10)vs 1.26(1.22,1.34)and 1.23(1.14,1.32);FWs:8.04(6.70, 8.71)mm vs 6.16(4.86,7.08)mm and 6.93(6.41,7.65)mm,exophthalmos:20.10(18.56,22.15)mm vs 15.40(14.87,16.60)mm and 14.73(13.40,16.07)mm,all P<0.05]. The reference value of SIR establishing based on SIRs of NC group is less than 1.37. In total 129 TAO patients,55 patients(with 106 eyeballs)have a clinical activity score(CAS). Then,these eyeballs were grouped to activity and non-activity(grouped by CAS≥3),and the baseline group difference of these 2 groups was not statistically significant. The SIRs and exophthalmos of activity group were higher than the non-activity group[SIRs:1.70(1.45,2.33)vs 1.41(1.25,1.75); exophthalmos:(20.38 ± 2.40)mm vs(19.05 ± 3.70)mm,all P<0.05]. But the difference of FWs of these two groups was not statistically significant(P>0.05). The SIRs and CAS had a positive correlation(r=0.580,P=0.000),through the receiver operating characteristic curve(ROC)we get the best diagnostic performance of TAO activity when the SIR≥1.56(sensibility=65.6%,specificity=89.1%,AUC=0.815,P=0.000). Conclusion The signal intensity ratio of extraocular muscle and ipsilateral white matter may discriminate the activity of TAO early as a quantitative indicator, reflecting its efficacy,and is worth clinically generalizing.

BACKGROUND: Both proximal femoral nail and hemiarthroplasty have been applied in the treatment of unstable intertrochanteric fractures in osteoporotic patients. However, which has better curative efficacy is still under discussion.OBJECTIVE: To investigate the clinical effectiveness of proximal femoral nail versus hemiarthroplasty in the treatment of unstable intertrochanteric fracture in osteoporotic patients.METHODS: Sixty-seven patients diagnosised with unstable intertrochanteric fractures and osteoporosis were selected,and were randomly divided into two groups, followed by treated with hemiarthroplasty (group 1, n=35)) and proximal femoral nail (group 2, n=32), respectively. The operation time, intraoperative blood loss, length of incision, postoperative time in bed, hospitalization time and complications were recorded and compared between two groups. Harris hip scores were used to evaluate the preoperative and postoperative hip function.RESULTS AND CONCLUSION: (1) In the group 1, the operation time, intraoperative blood loss and length of incision were more than those in the group 1, and the postoperative time in bed was less than that in the group 2 (P < 0.05).However, the healing and hospitalization time did not differ significantly between two groups (P > 0.05). (2) No significant difference was observed in the excellent and good rate in Harris hip scores between two groups at the last follow-up (P >0.05). The postoperative pain scores in the group 1 were significantly superior to those in the group 2 (P < 0.05). (3)There were 1 case of delayed union and 1 case of lateral hip appearing with pain in the group 2. At the last follow-up, all patients healed completely, and no prosthesis dislocation, loosening or infection was found. (4) To condude,hemiarthroplasty provides early functional recovery and fewer complications, but with much surgical trauma. Proximal femoral nail shows similar treatment outcomes with hemiarthroplasty; therefore, it is a kind of alternative treatment strategy for unstable intertrochanteric fractures.

A mammalian nonclassical secretion sequence derived from mouse Engrailed2 homeoprotein (En2) was used to direct the secretion of the enhanced green fluorescent protein from Pichia pastoris. This signal peptide conferred the transport of enhanced green fluorescent protein into periplasm through an endoplasmic reticulum-golgi independent pathway, without inducing severe unfolded protein response as compared with Saccharomyces cerevisae α-factor preprosequence. This study implies that this mammalian nonclassical signal peptide could be developed as a useful tool for delivering cargoes to the cell surface of yeast.

OBJECTIVETo explore whether bariatric surgery can decrease the incidence of obesity-related tumors in obesity patients.

METHODSRelevant studies comparing the incidence of obesity-related tumors in obesity patients between bariatric surgery and non- bariatric surgery were identified by search of PubMed, Medline, EBSCO, High Wire Press, OVID, EMbase, China hownet (CNKI) and Wanfang databases since the self-built database. In strict accordance with the standard after the screening, literature quality and extracted data were evaluated. Review manager 5.2 software was used to perform meta-analysis and sensitivity analysis. Inverted funnel chart was used to investigate the publication bias.

RESULTSFive articles including 108 954 patients were enrolled in the analysis. Among them, 26 218 cases were bariatric surgery group, and 82 736 cases of non-surgical weight loss were the control group. Meta analysis showed that bariatric surgery could obviously decrease the incidence of postoperative obesity-related tumor(RR=0.60, 95% CI:0.45-0.80, P=0.0005). Subgroup analysis showed that cancer risk difference of obesity-related tumor in male patients was not significant between two group, while the postoperative incidence of obesity-related tumor of female patients in bariatric surgery group was significantly lower compared to those female patients in control group(RR=0.68, 95% CI:0.61-0.77, P<0.01). During follow-up of 1 to 10 years, the incidence of obesity-related tumor in bariatric surgery group was significantly lower than that in control group(P<0.05). When follow-up was more than 10 years, the incidence of obesity-related tumors was similar between two groups(P=0.70).

CONCLUSIONBariatric surgery can decrease the overall risk of obesity-related cancer, especially for female patients, but with the prolongation of time, such effect of bariatric surgery is not obvious.

Eighteen patients with early cancer and precancerous lesions of esophagogastric junction underwent multiband mucosectomy (MBM) in Yangzhou First People's Hospital from January 2013 to February 2014.The clinicopathological data of patients were analyzed retrospectively and the short-term efficacy and safety of MBM were evaluated.Operations were successful in all 18 cases.The mean operative time was 35.8 min.Intraoperative bleeding occurred in 3 cases and successfully managed by endoscopic hemostasis.Small perforation occurred in 1 patient and was closed by metal clips.Pathological examination showed mucosal cancer in 5 cases,high-grade intraepithelial neoplasia in 8 cases and low-grade intraepithelial neoplasia in 5 cases.No relapse of cancer was found during follow-up.Results indicate that MBM is an effective and safe method in treatment of early cancer and precancerous lesions in the esophagogastric junction.