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.

Objective:To explore the association between A Body Shape Index (ABSI) and sarcopenia in Chinese older adults.Methods:Totally 1 728 participants in waves 1 and 3 of the China Health and Retirement Longitudinal Survey (CHARLS) were enrolled in this cohort-based cross-sectional analysis. ABSI was calculated by using anthropometric measurements from CHARLS. According to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus update on sarcopenia, low muscle strength and low muscle mass were used as the diagnostic criteria for sarcopenia. Logistic regression and restricted cubic spline (RCS) were used to assess the relationship between ABSI and sarcopenia, and subgroup and interaction analyses were conducted to evaluate the influence of other factors on this association.Results:High ABSI showed a significant association with the risk of sarcopenia among older adults in China, and RCS analysis demonstrated a positive linear correlation between ABSI and sarcopenia. Additionally, the relationship of ABSI with sarcopenia was significantly modified by educational level and depressive status.Conclusion:ABSI, a novel anthropometric measure, serves as an effective threshold for assessing sarcopenia risk in the Chinese older population, providing a basis for developing clinical interventions and public health strategies for the prevention and early identification of sarcopenia.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective:To explore the association between A Body Shape Index (ABSI) and sarcopenia in Chinese older adults.Methods:Totally 1 728 participants in waves 1 and 3 of the China Health and Retirement Longitudinal Survey (CHARLS) were enrolled in this cohort-based cross-sectional analysis. ABSI was calculated by using anthropometric measurements from CHARLS. According to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus update on sarcopenia, low muscle strength and low muscle mass were used as the diagnostic criteria for sarcopenia. Logistic regression and restricted cubic spline (RCS) were used to assess the relationship between ABSI and sarcopenia, and subgroup and interaction analyses were conducted to evaluate the influence of other factors on this association.Results:High ABSI showed a significant association with the risk of sarcopenia among older adults in China, and RCS analysis demonstrated a positive linear correlation between ABSI and sarcopenia. Additionally, the relationship of ABSI with sarcopenia was significantly modified by educational level and depressive status.Conclusion:ABSI, a novel anthropometric measure, serves as an effective threshold for assessing sarcopenia risk in the Chinese older population, providing a basis for developing clinical interventions and public health strategies for the prevention and early identification of sarcopenia.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective·To investigate the performance and psychological mechanisms of inhibitory control in patients with alcohol use disorder(AUD)under different emotional contexts,and to examine the influence of emotion regulation difficulties on inhibitory control.Methods·A total of 28 male AUD inpatients(AUD group)and 28 age-and education-matched healthy controls(HC group)were recruited.The emotional Go/Nogo task(angry/neutral facial expressions)was used to evaluate the subjects'behavioral inhibition,and the hierarchical drift-diffusion model(HDDM)was used to quantify the cognitive parameters(drift rate,decision threshold,and non-decision time).The Difficulties in Emotion Regulation Scale(DERS)and Alcohol Use Disorder Identification Test(AUDIT)were used for clinical evaluation.The moderated mediation effects were tested by bootstrap method.Results·The AUD group scored higher than the HC group on the DERS total score and all sub-dimensions(goal-directed behavior,impulse control,strategy access,and emotional clarity),and the difference was statistically significant(all P<0.05).At the behavioral level,compared with the HC group,the AUD group had elevated commission error rates[F(1,54)=8.62,P=0.005]and omission error rates[F(1,54)=4.28,P=0.043],and the reaction time of angry face stimuli was generally prolonged[F(1,54)=12.26,P=0.001].Cognitive modeling showed that the drift rate of the AUD group was significantly lower than that of the HC group[F(1,54)=15.56,P<0.001],indicating impaired information processing efficiency.The moderated mediation model showed that,under the condition of angry face stimuli,the drift rate partially mediated the relationship between group and commission error rate,and the total indirect effect value was 9.564(95%CI 3.874?16.387).Further analysis showed that the conditional indirect effect increased to 10.133(95%CI 3.963?17.927)at high levels of emotion regulation difficulty(one standard deviation above the mean),and to 9.011(95%CI 3.778?14.921)at low levels(one standard deviation below the mean).Conclusion·The deficits in information processing efficiency of AUD patients partly explains the impairment of inhibitory control,and this effect is associated with individual emotion regulation capacity.It is suggested that abnormal processing of social threat information may be an important factor affecting the impairment of inhibitory control in AUD patients,especially in individuals with weak emotion regulation ability.

Objective:To explore the clinical effects and value for application of the tibial flap of the second toe with the vascular pedicle including a plantar vein on the reconstruction of fingertip soft tissue defects.Methods:From October 2020 to August 2022, retrospective analysis of 12 patients (12 digits) were treated at the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital for small soft tissue defects of fingertip. The patients were 9 males and 3 females and aged 29-54 years, at 38 years in average. The fingertip defects were measured at approximately 1.2 cm × 0.8 cm to 1.2 cm × 1.2 cm. In the surgery, a tibial flap of second toe was designed to reconstruct the defect in fingertip. The flap were designed on the tibial of second toe without an extended incision in dorsal foot. The pedicle of the flap carried with the lateral proper digital artery, a nerve and the plantar vein of the second toe. At the recipient site, the artery, nerve and vein carried by the pedicle of the flap were end-to-end anastomosed with the digital artery, digital nerve and subcutaneous vein of the finger. The flaps were measured at 1.5 cm×1.0 cm - 1.5 cm×1.5 cm in size. All donor sites were reconstructed with skin grafts from the ipsilateral calf. Scheduled postoperative follow-ups were conducted at the outpatient clinic. The Michigan Hand Function Questionnaire (MHQ) evaluation criteria was employed to assess the recovery of hand function, and Total Active Movement (TAM) was used to evaluate the recovery of range of motion of the interphalangeal joints of the affected fingers.Results:All 12 flaps in the fingertips survived. Postoperative follow-ups lasted from 6 months to 2 years, with an average of 11 months. One flap was slightly bloated and a flap aesthetic surgery was followed at 3 months after the primary reconstructive surgery, and the rest of flaps were all in good appearance. TPD was found at 12 -14 mm for all flaps at 9 months after surgery. All donor sites in the feet and calfs had primary healing, without a contracture or rupture of skin graft or an obvious dysfunction at the donor sites. According to the evaluation criteria of the MHQ, 8 patients were very satisfied with the overall appearance of the hand, and 4 were satisfied. Finger movement was evaluated according to TAM criteria, all 12 fingers were rated excellent.Conclusion:Reconstruction of a fingertip defect with a tibial flap of the second toe with the vascular pedicle including a plantar vein of the second toe has a good clinical efficacy. It has advantages in flap harvest, avoids an extended incision on dorsal foot, and makes a minimal damage to the donor site.

Background and purpose:Gastric cancer,as one of the most common malignant tumors,requires early diagnosis and treatment to improve patient prognosis.This study,based on serum quantitative proteomics research of early-stage gastric cancer patients and non-gastric cancer patients,aims to identify potential diagnostic biomarkers for early gastric cancer.Methods:Serum samples from primary gastric cancer patients and healthy control individuals were collected from Lanzhou University Second Hospital between June and December 2023,following inclusion and exclusion criteria.A protein spectral library was established using Data-Dependent Acquisition(DDA)mode,and each sample was analyzed using Data-Independent Acquisition(DIA)mode.The STRING database was used to analyze protein-protein interactions of upregulated proteins in gastric cancer serum.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)were used to analyze the pathways and functional annotations of the corresponding genes.Gene expression levels in gastric cancer and non-gastric cancer tissues were analyzed using GEPIA 2,and overall survival of each gene in gastric cancer was analyzed using Kaplan-Meier Plotter.Differential gene expression in clinical gastric cancer and adjacent tissues was validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR)This study was approved by the Ethics Committee of Lanzhou University Second Hospital(Ethical No.:2023A-459)and was exempt from the informed consent.Results:Finally,serum samples from 30 primary gastric cancer patients,29 healthy control individuals,along with the para-cancerous tissues from 8 patients were collected.A total of 666 intersecting proteins were identified through serum quantitative proteomics.Among them,16 proteins showed upregulated expression and 22 proteins showed downregulated expression in the gastric cancer group(P＜0.05,|FC|≥1.5).STRING database analysis showed that 10 upregulated proteins were involved in interaction networks.KEGG and GO analysis indicated that these genes were closely related to the biological processes of cancer occurrence and development.GEPIA 2 and Kaplan-Meier Plotter analysis showed that 6 genes,B2M,TAGLN2,CTSD,HSP90AB1,SH3BGRL3,and CFL1,which were highly expressed in the gastric cancer group(P＜0.05)and associated with poor prognosis.Clinical verification by qRT-PCR confirmed that TAGLN2,CTSD,SH3BGRL3,CFL1 and HSP90AB1 were highly expressed in gastric cancer tissues(P＜0.05).Conclusion:TAGLN2,CTSD,SH3BGRL3,CFL1,and HSP90AB1 have the potential to serve as clinical early gastric cancer diagnostic serum biomarkers,which may facilitate early diagnosis and treatment of gastric cancer.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Objective·To investigate the performance and psychological mechanisms of inhibitory control in patients with alcohol use disorder(AUD)under different emotional contexts,and to examine the influence of emotion regulation difficulties on inhibitory control.Methods·A total of 28 male AUD inpatients(AUD group)and 28 age-and education-matched healthy controls(HC group)were recruited.The emotional Go/Nogo task(angry/neutral facial expressions)was used to evaluate the subjects'behavioral inhibition,and the hierarchical drift-diffusion model(HDDM)was used to quantify the cognitive parameters(drift rate,decision threshold,and non-decision time).The Difficulties in Emotion Regulation Scale(DERS)and Alcohol Use Disorder Identification Test(AUDIT)were used for clinical evaluation.The moderated mediation effects were tested by bootstrap method.Results·The AUD group scored higher than the HC group on the DERS total score and all sub-dimensions(goal-directed behavior,impulse control,strategy access,and emotional clarity),and the difference was statistically significant(all P<0.05).At the behavioral level,compared with the HC group,the AUD group had elevated commission error rates[F(1,54)=8.62,P=0.005]and omission error rates[F(1,54)=4.28,P=0.043],and the reaction time of angry face stimuli was generally prolonged[F(1,54)=12.26,P=0.001].Cognitive modeling showed that the drift rate of the AUD group was significantly lower than that of the HC group[F(1,54)=15.56,P<0.001],indicating impaired information processing efficiency.The moderated mediation model showed that,under the condition of angry face stimuli,the drift rate partially mediated the relationship between group and commission error rate,and the total indirect effect value was 9.564(95%CI 3.874?16.387).Further analysis showed that the conditional indirect effect increased to 10.133(95%CI 3.963?17.927)at high levels of emotion regulation difficulty(one standard deviation above the mean),and to 9.011(95%CI 3.778?14.921)at low levels(one standard deviation below the mean).Conclusion·The deficits in information processing efficiency of AUD patients partly explains the impairment of inhibitory control,and this effect is associated with individual emotion regulation capacity.It is suggested that abnormal processing of social threat information may be an important factor affecting the impairment of inhibitory control in AUD patients,especially in individuals with weak emotion regulation ability.