The research and development of innovative drug have progressed remarkably, but the long development circle and high failure rate have become the bottleneck. Drug repurposing, discovering new indications of approved drugs, is a strategy to overcome these obstacles. By exploring new indications for approved drugs, rapid progress has been made in basic research and clinical translation in recent years. Rich resources of drugs, proven security, efficient development workflow and reduced cost are core advantages of this strategy, making the strategy a crucial direction of optimizing the pipeline of drug research and development. This review systematically summarizes drug repurposing cases that have received clinical approval over the past five years, and proposes core strategies for drug repurposing, including approaches based on targets, pathways, drug similarity, post-treatment phenotypes, and clinical side effects, aiming to provide some strategic guidance for drug repurposing efforts.

It has been demonstrated that long-term space flights have a significantly greater impact on the cardiovascular, skeletal, and nervous systems of astronauts. The structural and functional alterations in the skeletal and muscular systems resulting from exposure to weightlessness can lead to the development of low back pain, significantly impairing the ability of astronauts to perform tasks and respond to emergencies. Both space flight and simulated microgravity have been shown to result in low back pain among astronauts, with the following factors identified as primary contributors to this phenomenon. The occurrence of intervertebral disc (IVD) edema results in the stimulation of type IV mechanoreceptors, which subsequently activate nociceptive afferents. The protrusion of an IVD causes compression of the spinal nerve roots. Furthermore, the elongation of the vertebral column and/or the diminished lumbar curvature of the spine exert traction on the dorsal root nerves. Paravertebral muscle degeneration leads to the inhibition of decreased nociceptive activity of the wide-dynamic range neurons of the spinal dorsal horn. Moreover, endogenous pain descending facilitation triggered by conditioning stimulation can be enhanced via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.

The injury of the posterior Angle of the medial meniscus of the knee joint is very common in clinic, and the arthroscopic treatment of the knee joint has been the first choice. However, there are many difficulties in arthroscopic treatment, such as narrow space in the medial posterior corner of the knee joint, insufficient space to deal with the injured meniscus, varion and lateral rotation under 30° flexion, release of the medial collateral ligament of the knee joint, and expansion of the knee joint cavity spinner, all of which could expose and expand the medial space of knee joint. Therefore, it is necessary to master and balance the use to avoid collateral injury. It is also necessary to determine the cause of meniscus injury during arthroscopic treatment, such as degenerative injury, simple meniscus repair and forming can hardly solve the pain of patients. Anterior cross injury is easy to cause instability of the knee joint, which is closely related to the injury of the posterior angle of the medial meniscus of the knee joint. In order to achieve the maximum therapeutic effect, physiological repair should be performed at the same time. There are various types of medial meniscus posterior angle injury, among which the Ramp injury, root fracture and laminae meniscus injury are greatly affected by joint degeneration, narrow knee space or knee stability, and all influencing factors should be fully considered in treatment.
Humans ; Arthroscopy/methods* ; Tibial Meniscus Injuries/surgery* ; Knee Joint/surgery* ; Menisci, Tibial/surgery* ; Knee Injuries/surgery*

OBJECTIVES: To study the impact of different induction remission therapies on the nutritional status of children with Crohn's disease (CD). METHODS: A retrospective analysis was conducted on the medical data of 188 children with CD who received induction remission therapy at the Children's Hospital, Zhejiang University School of Medicine from January 2013 to May 2023. The effects of three induction remission therapies-exclusive enteral nutrition (EEN), corticosteroids, and infliximab (IFX)-on height, weight, hemoglobin, and trace elements were compared. RESULTS: After induction remission therapy, the weight-for-age Z scores and serum levels of hemoglobin and albumin in all three groups significantly increased (P<0.05), while the height-for-age Z scores showed no change (P>0.05). The levels of folic acid, 25-hydroxy vitamin D, serum iron, and total calcium increased, and serum copper levels decreased in the EEN and IFX groups (P<0.05). Vitamin B₁₂ levels improved in the EEN group (P<0.05). CONCLUSIONS EEN, corticosteroids, and IFX may effectively improve the weight-for-age Z scores and serum levels of hemoglobin and albumin in children with CD. EEN and IFX seem to be superior to corticosteroid therapy in improving 25-hydroxy vitamin D, folic acid, serum iron, and total calcium levels.
Humans ; Crohn Disease/blood* ; Child ; Male ; Female ; Retrospective Studies ; Adolescent ; Nutritional Status ; Infliximab/therapeutic use* ; Child, Preschool ; Enteral Nutrition ; Adrenal Cortex Hormones/therapeutic use*

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Exercise-induced analgesia (EIA) refers to the elevation of pain thresholds and reduction in sensitivity to noxious stimuli achieved through exercise training. As a non-pharmacological treatment strategy, exercise therapy has demonstrated positive effects on both acute and chronic pain. Increasing evidence indicates that modulation of glial cell activity is an important mechanism underlying analgesia. Spinal glial cells contribute to the development and maintenance of pathological pain by promoting pain signal transmission through inflammatory responses and synaptic remodeling. Exercise can differentially regulate microglia and astrocyte activity, inhibiting multiple inflammatory signaling pathways, such as P2X4/P2X7 purinergic receptors, brain-derived neurotrophic factor (BDNF)/phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR), interleukin (IL)-6/Janus kinase (JAK) 2/signal transducer and activator of transcription 3 (STAT3), p38-mitogen-activated protein kinases (MAPK), and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), thereby reducing the release of pro-inflammatory cytokines, decreasing inflammatory and nociceptive hypersensitivity, and alleviating pathological pain. This review also summarized the effects of different exercise intensities, durations, and frequencies on glial cell responses in order to provide a theoretical foundation for optimizing exercise-based interventions for pathological pain conditions.
Humans ; Microglia/metabolism* ; Astrocytes/metabolism* ; Exercise/physiology* ; Signal Transduction ; Analgesia/methods* ; Spinal Cord/cytology* ; Exercise Therapy ; Pain Management/methods* ; Animals ; Brain-Derived Neurotrophic Factor/metabolism*

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To investigate the correlation between the combined assessment of preoperative 5-factor modified frailty index(mFI-5)and Naples prognostic score(NPS)with overall survival in patients with unresectable hepatocellular carcinoma(uHCC)following interventional therapy.Methods A retrospective cohort study enrolled 292 patients with uHCC who underwent interventional therapy at the Department of Hepatobiliary Pancreatic Surgery of the Second Affiliated Hospital in Army Medical University from October 2017 to December 2021.Patients were stratified into high-risk and low-risk groups based on mFI-5(≥1),NPS(≥3),and CONUT(≥4)scores.Propensity score matching(PSM)was performed to balance baseline characteristics(post-matching n=186).The primary endpoint was overall survival(OS),analyzed using Kaplan-Meier curves with log-rank tests.The predictive performance of combined indicators was evaluated by receiver operating characteristic(ROC)curves,and prognostic factors were assessed via Cox regression analysis.Results After PSM,baseline characteristics(including age,tumor markers,and treatment-related parameters)showed no significant differences between the two groups.Survival analysis demonstrated a 2.252-fold higher risk of death in the mFI-5 plus NPS high-risk group(95%CI:1.60～3.18,P<0.001).The combination of mFI-5 and NPS scores yielded an area under curve(AUC)of 0.718 for predicting 3-year overall survival,significantly outperforming either index alone(P=0.007).Multivariable Cox regression analysis identified that dual positivity for mFI-5 and NPS(HR=1.46;95%CI:1.01～2.11,P=0.044),portal vein tumor thrombosis(HR=1.49;95%CI:1.03～2.16,P=0.035),tumor diameter>5 cm(HR=2.01;95%CI:1.27～3.17,P=0.003),Barcelona clinic liver cancer(BCLC)stage C disease(HR=2.05;95%CI:1.37～3.07,P<0.001)were independent predictors of poor prognosis.Postoperative combination targeted therapy and immunotherapy was associated with significantly reduced mortality risk(HR=0.57;95%CI:0.39～0.81,P=0.002).Conclusion The combination of mFI-5 and NPS scores is significantly associated with overall survival in patients with unresectable hepatocellular carcinoma(uHCC)undergoing locoregional therapy,providing a validated tool for clinical risk stratification and personalized treatment planning.