The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

OBJECTIVES: To investigate the mechanism through which salidroside inhibits proliferation of gastric cancer (GC) cells focusing on glucose metabolic reprogramming pathways. METHODS: High-throughput sequencing combined with bioinformatics analysis was employed to identify the potential targets of salidroside in human GC MGC-803 cells. Liposome-mediated transfection experiments were carried out to validate the functional and mechanistic roles of these targets. CCK-8 and colony formation assays were used to assess the effects of salidroside on GC cell viability and clonogenic ability. qRT-PCR, Western blotting, and biochemical assay kits were used to analyze the regulatory effects of salidroside on the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway in GC cells. RESULTS: Bioinformatics analysis suggested that the tumor-suppressive factor miR-1343-3p negatively regulated the key glycolytic enzyme gene oxoglutarate dehydrogenase-like (OGDHL) in GC cells, and OGDHL and pyruvate dehydrogenase E1 subunit beta (PDHB) were both significantly upregulated in GC tissues, which was close by correlated with reduced survival rates of GC patients. In MGC-803 cells, salidroside treatment significantly enhanced the expression level of miR-1343-3p and downregulated OGDHL expression, resulting in disruption of the stability of PDHB, reduced pyruvate oxidative decarboxylation, and consequently decreased production of acetyl-CoA and ATP. CONCLUSIONS Salidroside inhibits GC cell proliferation possibly by regulating the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway, which provides new insights into its anti-tumor mechanisms and suggests new strategies for targeted therapy for GC.
Humans ; Stomach Neoplasms/pathology* ; MicroRNAs/genetics* ; Cell Proliferation/drug effects* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Glucose/metabolism* ; Pyruvate Dehydrogenase (Lipoamide)/metabolism*

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective To observe the value of right ventricle modified myocardial performance index(RV-Mod-MPI)for evaluating maternal obstetric antiphospholipid syndrome(OAPS)involving fetal right ventricular function.Methods Forty-five pregnant women with maternal OAPS(OAPS group)and 60 healthy pregnant women(control group)were prospectively enrolled.Fetal RV-Mod-MPI was obtained with tricuspid and pulmonary valve flow images by applying pulsed wave Doppler(PW).Late pregnancy conditions and data of newborns after delivery were recorded.The indexes were compared between groups.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was used to assess the efficacy of fetal RV-Mod-MPI for predicting adverse pregnancy outcomes in OAPS group.Results Compared with those in control group,OAPS group had higher fetal RV-Mod-MPI values,lower newborn birth weight and lower Apgar score at 1 min after birth,as well as higher probability of adverse pregnancy outcomes(all P＜0.05).The AUC of fetal RV-Mod-MPI for predicting adverse pregnancy outcome in OAPS group was 0.726.Conclusion RV-Mod-MPI could be used to evaluate maternal OAPS involving fetal right ventricular function and predict adverse pregnancy outcomes.

Inflammatory response is one of the key mechanisms of cerebral ischemia/reperfusion injury(CIRI),which seriously affects the prognosis of patients.In recent years,it has been found that long non-coding RNA(LncRNA)is closely related to the inflammatory response of cerebral ischemia/reperfusion injury,and can affect the development and prognosis of CIRI through multiple pathways.The article reviews and summarizes the LncRNAs and their action pathways affecting the inflammatory response in CIRI.The article preliminary explores the possible mechanisms by which LncRNAs affect CIRI,and also briefly summarizes the drugs related to LncRNA therapy.In order to provide new therapeutic targets and research ideas for the treatment of CIRI.

Objective To explore the application value of RMNES combined with comprehensive rehabilitation for consciousness impairment caused by senile brain injury.Methods A retrospec-tive analysis was conducted on 160 elderly patients with consciousness disorders caused by brain injury admitted in our hospital between January 2020 and November 2023.According to treatment regiments,they were divided into comprehensive rehabilitation group(Group Ⅰ,53 cases),com-prehensive rehabilitation followed by RMNES group(Group Ⅱ,54 patients),and simultaneous indoor comprehensive rehabilitation and RMNES(Group Ⅲ,53 patients).At 1 week after treat-ment,electroencephalogram(EEG)grade,brainstem auditory induction(BAEP)grade,cerebral hemodynamic parameters[including relative cerebral blood flow(rCBF),relative cerebral blood volume(rCBV),and mean blood flow velocity(Vm)],Disability Rating Scale(DRS)score,and Glasgow Coma Scale(GCS)score were compared among the three groups.Results After 1 week of treatment,the ratios of EEG grade Ⅰ,EEG grade Ⅱ and BAEP grade Ⅰ,rCBV,rCBF and Vm values and GCS score were increased,while the ratios of EEG grade V and BAEP grade Ⅲ,and DRS score were decreased when compared with the levels before treatment(P＜0.05).Significant differences were observed in EEG grade and BAEP grade among the 3 groups after 1 week of treatment(P＜0.01);Group Ⅲ had obviously higher rCBV,rCBF,Vm and GCS score and lower DRS score than Groups Ⅰ and Ⅱ(P＜0.05).There was no statistical difference in the incidence of adverse reactions in Groups Ⅰ,Ⅱ and Ⅲ(3.77％vs 7.41％vs 7.55％,x2=0.830,P=0.660).Conclusion Simultaneous indoor comprehensive rehabilitation and RMNES treatment achieves more significant efficacy for elderly patients with brain injury-caused consciousness disorders,and it can improve electrophysiological activities of brain nerves,enhance cerebral hemodynamics,and promote the recovery of consciousness.

Hip surgery is often associated with moderate to severe postoperative pain due to exten-sive invasion.A safe and effective postoperative pain treatment can promote patients'recovering activities and facilitate the early functional recovery of the hip after the surgery.Although the routinely used intrave-nous self-controlled analgesia has an exquisite analgesic effect,it carries the risks of postoperative nausea and emesis,excessive sedation,intestinal paralysis,and even respiratory depression.As an alternative to transversus abdominis plane block(TAPB),lumbar quadratus block(QLB)has been gradually applied to the hip joint surgery.In this paper,we review the anatomical basis and characteristics of QLB and its clini-cal application in hip surgery,in order to provide the postoperative analgesia application of QLB.

Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.