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 differences in the whole-brain functional connectivity characteristics of magnetoencephalography gamma sub-band in resting state between patients with depression with high and low suicidal ideation.Methods:Clinical data of 60 patients with depression (depression group) who visited the Department of Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University from October 2021 to June 2024 were prospectively collected, including 20 males and 40 females aged 16-41 years. During the same period, 75 healthy controls (healthy control group) were recruited, matched for gender and age, comprising 33 males and 42 females, aged 18-43 years. The Hamilton Depression Scale-17 items (HAMD-17) was used to assess the degree of depression in patients, and the score of the third item was used to divide the patients into a high suicidal ideation group of 37 cases (2-3 points) and a low suicidal ideation group of 23 cases (0-1 points). The Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) was used to assess the intensity of suicidal ideation in patients in the last week and at the most severe stage. Brain imaging data of the subjects were collected using a CTF-275 channel magnetoencephalography device and a 3 T magnetic resonance imaging device. The functional connectivity matrix of the gamma sub-band depression group, healthy control group, high suicidal ideation group, and low suicidal ideation group was calculated using the envelope correlation method. The network-based statistics (NBS) algorithm was used to correct for multiple comparisons and compare the differences in brain network functional connectivity between the depression group/healthy control group and between the high/low suicidal ideation groups.Results:Compared with the healthy control group, the functional connectivity between the bilateral middle frontal gyrus, right inferior frontal gyrus orbital part, right anterior cingulate gyrus, left middle frontal gyrus orbital part, and right superior parietal lobule in the depression group was significantly enhanced in the low gamma frequency band (30-60 Hz) ( θ=3, P=0.042). Compared with the low suicidal ideation group, the functional connectivity between the right amygdala as a central node and the right superior frontal gyrus, left hippocampus, right upper temporal pole, and left transverse temporal gyrus in the high suicidal ideation group was significantly enhanced in the high gamma frequency band (60-90 Hz) ( θ=3, P=0.049). Conclusion:In the low gamma frequency band, patients with depression have neural dysfunction mainly in the frontal lobe. In the high gamma frequency band, patients with high suicidal ideation have functional connectivity abnormalities centered on the amygdala.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To explore the differences in the whole-brain functional connectivity characteristics of magnetoencephalography gamma sub-band in resting state between patients with depression with high and low suicidal ideation.Methods:Clinical data of 60 patients with depression (depression group) who visited the Department of Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University from October 2021 to June 2024 were prospectively collected, including 20 males and 40 females aged 16-41 years. During the same period, 75 healthy controls (healthy control group) were recruited, matched for gender and age, comprising 33 males and 42 females, aged 18-43 years. The Hamilton Depression Scale-17 items (HAMD-17) was used to assess the degree of depression in patients, and the score of the third item was used to divide the patients into a high suicidal ideation group of 37 cases (2-3 points) and a low suicidal ideation group of 23 cases (0-1 points). The Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) was used to assess the intensity of suicidal ideation in patients in the last week and at the most severe stage. Brain imaging data of the subjects were collected using a CTF-275 channel magnetoencephalography device and a 3 T magnetic resonance imaging device. The functional connectivity matrix of the gamma sub-band depression group, healthy control group, high suicidal ideation group, and low suicidal ideation group was calculated using the envelope correlation method. The network-based statistics (NBS) algorithm was used to correct for multiple comparisons and compare the differences in brain network functional connectivity between the depression group/healthy control group and between the high/low suicidal ideation groups.Results:Compared with the healthy control group, the functional connectivity between the bilateral middle frontal gyrus, right inferior frontal gyrus orbital part, right anterior cingulate gyrus, left middle frontal gyrus orbital part, and right superior parietal lobule in the depression group was significantly enhanced in the low gamma frequency band (30-60 Hz) ( θ=3, P=0.042). Compared with the low suicidal ideation group, the functional connectivity between the right amygdala as a central node and the right superior frontal gyrus, left hippocampus, right upper temporal pole, and left transverse temporal gyrus in the high suicidal ideation group was significantly enhanced in the high gamma frequency band (60-90 Hz) ( θ=3, P=0.049). Conclusion:In the low gamma frequency band, patients with depression have neural dysfunction mainly in the frontal lobe. In the high gamma frequency band, patients with high suicidal ideation have functional connectivity abnormalities centered on the amygdala.

Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Objective:To explore the mechanism of Jianpi Qingchang Decoction in the treatment of UC by integrating network pharmacology, bioinformatics, molecular docking and experimental verification.Methods:The effective components and targets of Jianpi Qingchang Decoction were obtained from TCMSP database, and UC data sets GSE16879, GSE48958 and GSE75214 were obtained from GEO database, and differentially expressed genes were screened; intersection targets were obtained through Venn diagram, and GO function and KEGG pathway enrichment analysis was performed. An intersection target PPI network was constructed using STRING database and topology analysis was performed; hub genes were screened through lasso regression and the expression consistency of core targets in the dataset was verified through logistic regression. A UC mouse model was established and hub genes were validated.Results:A total of 213 drug targets of Jianpi Qingchang Decoction were obtained, and 499 common intersection targets of GSE16879, GSE48958 and GSE75214 were obtained by differential gene expression analysis. Thirty intersection targets of Jianpi Qingchang Decoction and UC were obtained, mainly acting on IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, etc. PPI network topology analysis obtained 7 common intersection targets, including PTGS2, IL-1B, IL-6, MMP9, CXCL8, CCL2 and MMP2. IL-6 and MMP2 were selected as hub genes by lasso regression. Logistics regression analysis showed that IL-6 and MMP2 were risk factors for the disease. Compared with the model group, the expressions of IL-6 and MMP2 mRNA and protein in the colon tissue of the TCM group decreased ( P<0.05), and the morphology of colon tissue was improved compared with the model group. Conclusion:IL-6 and MMP2 are risk factors for UC, the therapeutic effect of Jianpi Qingchang Decoction is to mediate Il-17 signal pathway, TNF signal pathway and AGE-RAGE signal pathway in diabetic complications through the targets of IL-6, and MMP2, thereby treating UC.

Zhuye Shigaotang， first recorded in ZHANG Zhongjing's Synopsis of the Golden Chamber （《金匮要略》）， is a commonly used prescription for treating heat syndrome in modern times. However， physicians of the past dynasties have different opinions on the mechanism of Zhuye Shigaotang in disease treatment. Based on HUANG Yuanyu's theory of Qi circulation， this paper holds that the root cause of the diseases treated by Zhuye Shigaotang is the deficiency of spleen and stomach in the middle energizer and the dysfunction of ascending and descending. The failure of Yin ascending leads to the failure of Yang transformation， and the failure of Yang descending causes the failure of Yin generation. As a result， heat and fire become predominant in the heart， lung， and stomach， which causes Qi counterflow and fluid consumption. Based on this pathogenesis， Zhuye Shigaotang is mainly composed of pungent， warm， sweet， and cold herbs. The combination of these herbs can protect the spleen and stomach and recover the Qi movement in the middle energizer， thereby clearing heat and fire， descending Qi， and promoting the generation of Qi and fluid. In clinical practice， this prescription can be applied to treating the syndromes of deficiency in spleen and stomach， dysfunction of middle energizer in transportation， dysfunction of ascending and descending， excessive heat and fire， and Qi counterflow and fluid consumption. The interpretation of Zhuye Shigaotang from the theory of Qi circulation can provide a new idea for differentiating syndromes， seeking causes， and developing prescriptions， which broadens the scope of clinical application of this prescription and provides a reference for interpreting ZHANG Zhongjing's method of compatibility.

Objective:To analyze the clinical epidemiological characteristics and the prognostic risk factors of patients with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 2 245 HFRS patients who were admitted to the Second Affiliated Hospital of Air Force Medical University from September 2008 to December 2021 were enrolled. Clinical epidemiological data (including gender, age, onset season, onset region, case fatality rate, et al) of HFRS patients were analyzed. The clinical epidemiological characteristics of patients with HFRS in the 2008 to 2012, 2013 to 2017, and 2018 to 2021 groups were compared. Statistical comparisons were performed using chi-square test. The Bonferroni adjusted P-value method was used for pairwise comparisons between groups, and logistic regression analysis was used to screen and evaluate the risk factors associated with the prognosis of HFRS patients. Results:The age of 2 245 HFRS patients was (42.3±15.9) years old. Most of them were male (79.24%(1 779/2 245)), and the main incidence area was Xi′an City (69.53%(1 561/2 245)). There were 132 deaths with an overall case fatality rate of 5.88%. There were 1 088 patients (48.46%) from 2008 to 2012, 647 patients (28.82%) from 2013 to 2017, and 510 patients (22.72%) from 2018 to 2021, with a mortality rate of 7.17%(78/1 088), 5.10%(33/647) and 4.12%(21/510), respectively. From 2008 to 2021, both the number of HFRS cases and the case fatality rate had shown a fluctuating downward trend. There were significant differences in case fatality rate, age distribution, onset season, and onset region among patients in the different year groups ( χ2=6.84, 49.22, 83.47 and 19.29, respectively, all P<0.05). The results of pairwise comparisons showed that the proportion of patients aged >60 years in the 2018 to 2021 group (23.33%(119/510)) was higher than those in the 2008 to 2012 group (12.13%(132/1 088)) and the 2013 to 2017 group (12.36%(80/647)), and the differences were statistically significant (both P<0.05). The proportions of patients at large peak (October to December) were 62.35%(318/510) in the 2018 to 2021 group and 56.26%(364/647) in the 2013 to 2017 group, which were both lower than that in the 2008 to 2012 group (75.18%(818/1 088)), and the differences were both statistically significant (both P<0.05). The case fatality rate of patients aged >60 years was 9.67%(32/331), which was higher than those of patients aged <30 years (2.86%(16/559)) and patients aged 30 to 60 years (6.20%(84/1 355)), with statistically significant differences (both P<0.05). Univariate analysis showed that age 30 to 60 years, age >60 years, smoking, complicated with hypertension, hypotensive shock and hypoxemia were significantly correlated with the prognosis of HFRS patients (odds ratio ( OR)=2.243, 3.632, 1.484, 3.532, 79.422 and 143.955, respectively, all P<0.05). The results of multivariate logistic regression analysis indicated that complicated with hypertension ( OR=2.467, P=0.004), hypotensive shock ( OR=11.658, P=0.001), and hypoxemia ( OR=67.767, P<0.001) were the independent risk factors affecting the prognosis of HFRS patients. Conclusions:The prevalence of HFRS has shown new changing characteristics from 2008 to 2021. The numbers of HFRS patients and the case fatality rates show a downward trend, and the proportion of HFRS patients aged >60 years increases. Complicated with hypertension, hypotensive shock and development with hypoxemia are the independent risk factors for the prognosis of HFRS.