Depression is a psychiatric disorder whose main symptoms include low mood， loss of interest， anxiety， sleep disturbances， and changes in appetite. Orexin， a neuropeptide located in hypothalamic neurons， has a wide range of projections throughout the central nervous system and is involved in various behavioral modulations related to depression. This study systematically reviewed the effects of orexin and its receptor-related drugs on depression and found that orexin could exert complex regulatory effects on multiple brain regions by binding to related receptors， affecting emotions， sleep， anxiety， etc. The abnormal state of expression of plasma orexin in patients with depression was found. Exogenous orexin-A， selective orexin receptor 1 antagonists （SORA1s）， selective orexin receptor 2 antagonists （SORA2s）， and dual orexin receptor antagonists （DORAs） have demonstrated antidepressant-like effects in various animal models of depression. Among them， clinical trials involving exogenous orexin-A are relatively scarce. Drugs related to SORA1s and SORA2s， such as JNJ-61393215 and Setorexant， have made significant progress in the treatment of depression. DORAs， such as Suvorexant， Lemborexant， and Daridorexant， are primarily used to treat insomnia. Notably， Suvorexant has also shown potential in alleviating symptoms of anxiety and depression.

OBJECTIVE: To compare the clinical efficacy of jingjin needling combined with rehabilitation training and conventional acupuncture combined with rehabilitation training for post-stroke spastic paralysis. METHODS: A total of 60 patients with post-stroke spastic paralysis were randomly divided into an observation group and a control group, 30 cases in each one. Both groups received conventional rehabilitation training. In the observation group, jingjin needling was applied at tendon blockage points of the shoulder, elbow, wrist, hip, knee, and ankle. In the control group, conventional acupuncture was applied at Jianyu (LI15), Quchi (LI11), Hegu (LI4), Biguan (ST31), Fengshi (GB31), Taichong (LR3), etc. on the affected side. Treatment was given once daily, 5 days a week for 4 weeks in both groups. The scores of clinical spasticity index (CSI), modified Ashworth scale, modified Barthel index (MBI), and Fugl-Meyer assessment scale (FMA) were evaluated before and after treatment, and the onset time was compared between the two groups. RESULTS: After treatment, the scores of CSI and modified Ashworth scale were decreased compared with those before treatment (P<0.001), while the scores of MBI and FMA were increased compared with those before treatment (P<0.001) in the two groups. After treatment, the scores of CSI and modified Ashworth scale in the observation group were lower than those in the control group (P<0.05), the MBI score in the observation group was higher than that in the control group (P<0.05). There was no statistically significant difference in FMA scores between the two groups (P>0.05). The onset time of the observation group was earlier than that in the control group (P<0.05). CONCLUSION Both jingjin needling combined with rehabilitation training and conventional acupuncture combined with rehabilitation training can effectively treat post-stroke spastic paralysis, jingjin needling combined with rehabilitation training exhibits better therapeutic effect and rapider onset.
Humans ; Acupuncture Therapy ; Male ; Female ; Middle Aged ; Aged ; Stroke/complications* ; Adult ; Acupuncture Points ; Muscle Spasticity/etiology* ; Treatment Outcome ; Stroke Rehabilitation ; Paralysis/therapy* ; Combined Modality Therapy

OBJECTIVE: To evaluate the effects of acupuncture at Hegu (LI4), Taichong (LR3) and Sanyinjiao (SP6) on pain, anxiety, intrapartum blood loss, labor stage, and neonatal outcomes in primiparas. METHODS: One hundred primiparas were randomly divided into an acupuncture group (50 cases, 1 case was eliminated) and a control group (50 cases). The conventional obstetrical nursing was given in the control group. On the basis of the intervention in the control group, acupuncture was applied at bilateral Hegu (LI4), Taichong (LR3) and Sanyinjiao (SP6) in the acupuncture group. The delivery mode and labor stage, the scores of visual analogue scale (VAS) for uterine contraction pain and Hamilton anxiety scale (HAMA) before and after acupuncture, the intrapartum/postpartum blood loss and massive hemorrhage, as well as the neonatal Apgar score after 1, 5, and 10 min of birth, were compared in the two groups. RESULTS: The cesarean section rate was 4.1% (2/49) in the acupuncture group, which was superior to 10.0% (5/50) in the control group (P<0.05). In the acupuncture group, the time of latent phase of 2-cm cervical dilation, active phase, first and second stages of labor, and total labor stage was shorter than that in the control group (P<0.001), the intrapartum blood loss and massive hemorrhage rate were lower than those in the control group (P<0.001, P<0.05). After acupuncture, the VAS and HAMA scores were decreased compared with those before acupuncture in the acupuncture group (P<0.001), the VAS and HAMA scores were increased compared with those before acupuncture in the control group (P<0.001). In the acupuncture group, the VAS and HAMA scores after acupuncture were lower than those in the control group (P<0.001), the changes of the VAS and HAMA scores before and after acupuncture were larger than those in the control group (P<0.001). There were no statistical differences in neonatal Apgar scores between the two groups (P>0.05). CONCLUSION Acupuncture at Hegu (LI4), Taichong (LR3) and Sanyinjiao (SP6) can effectively alleviate the pain and anxiety, shorten the labor stage, reduce the intrapartum blood loss and incidence rate of massive hemorrhage, and promote spontaneous delivery, thereby enhancing maternal comfort and safety in primiparas.
Humans ; Female ; Pregnancy ; Acupuncture Points ; Acupuncture Therapy ; Adult ; Young Adult ; Labor, Obstetric ; Parity

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

OBJECTIVE: To explore clinical characteristics, lesion sites and correlation differences of different types of diabetic foot gangrene, and to provide evidence-based basis for clinical classification of diabetic foot gangrene. METHODS: A retrospective analysis was conducted on 266 patients with newly diagnosed diabetic foot gangrene who were admitted from January 2018 to December 2018, including 183 males and 83 females, aged from 35 to 92 years old with an average of (69.55±10.84) years old, and they were divided into wet gangrene group and dry gangrene group according to the different natures of gangrene. There were 139 patients in wet gangrene group, including 98 males and 41 females, aged from 35 to 90 years old with an average of (68.95±10.93) years old. There were 127 patients in dry gangrene group, including 85 males and 42 females, aged from 38 to 92 years old with an average of (70.21±10.75) years old. Body mass index (BMI), waist-to-hip ratio (WHR), body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, and Wagner grade between two groups were recorded to evaluate symptoms and signs. The white blood cell count (WBC), neutrophil percentage (NEUT%), and C-reactive protein (C-reactive protein), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) in peripheral blood between two groups were detected and compared to evaluate the infection status;the severity of diabetic peripheral neuropathy (DPN) was evaluated by using Toronto Clinical Scoring System (TCSS);the degree of pain in patients with diabetic foot gangrene was evaluated by numerical rating scale (NRS); ankle-brachial index (ABI) and popliteal artery blood flow velocity were used to evaluate the degree of arterial lesions. Spearman correlation analysis was used to analyze the correlations between gangrene TCSS, ABI and age, BMI, WHR, body temperature, calf skin temperature difference, WBC, NEUT%, CRP, ESR, PCT, IL-6, NRS, and Wagner classification indicators. RESULTS: The body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, Wagner grade, WBC, NEUT%, CRP, ESR, PCT, IL-6, TCSS score, ABI, and popliteal artery blood flow velocity in wet gangrene group were higher than those in dry gangrene group (P<0.01), and BMI, WHR, and NRS score in dry gangrene group were higher than those in wet gangrene group;the differences were all statistically significant (P<0.01). The results of Spearman correlation analysis showed TCSS score of gangrene patients was correlated with body temperature (r=0.214), calf skin temperature difference (r=0.364), WBC (r=0.240), NEUT% (r=0.291), CRP (r=0.347), ESR (r=0.167), PCT (r=0.241), IL-6 (r=0.316), and popliteal fossa arterial blood flow velocity (r=0.261) and Wagner grade (r=0.273) were positively correlated, and the differences were statistically significant (P<0.01). ABI was negatively correlated with age (r=-0.183), BMI (r=-0.252), WHR (r=-0.288), and NRS score (r=-0.354), and the differences were statistically significant (P<0.01). CONCLUSION Diabetic foot gangrene is an extremely difficult and critical disease. Wet gangrene has a significant synergic effect with infection and neuropathy, while dry gangrene is closely related to vascular occlusion. The main contradiction of gangrene could be revealed through blood vessels, nerves and infection, providing evidence-based basis for the selection of debridement timing, anti-infection strategies and revascularization, with the aim of reducing the risk of amputation.
Humans ; Male ; Female ; Aged ; Middle Aged ; Diabetic Foot/diagnosis* ; Aged, 80 and over ; Adult ; Retrospective Studies ; Gangrene/physiopathology* ; C-Reactive Protein

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

OBJECTIVE: To investigate the pharmacological mechanism of Compound Xuanju Capsule in the treatment of erectile dysfunction (ED) by using network pharmacology and molecular docking technology. METHODS: The active ingredients and targets of Compound Xuanju Capsule were screened using Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP). TTD, OMIM, DrugBank and GeneCards databases were used to obtain genes related to ED, and the union of the results was taken as the disease genes of ED. The common target of drug and disease was taken as the potential target of Compound Xuanju Capsule in ED, and the drug-disease interaction network was constructed by using Cytoscape software. The protein-protein interaction (PPI) network was constructed by using String database, which was then imported into Cytoscape to identify the key target. Based on the drug-disease intersection genes, GO and KEGG enrichment analyses were performed to predict the relevant signaling pathways and molecular mechanisms of Compound Xuanju Capsule for the treatment of ED. Autodock software was used to perform molecular docking between the active ingredients and the core targets. RESULTS: Forty chemical components of Compound Xuanju Capsule were screened, and 239 predicted targets were obtained. A total of 1 907 ED-related genes were screened, and 97 common targets were identified between Compound Xuanju Capsule and ED, among which the core targets included EGFR, ESR1, HIF1A, PTGS2, and STAT3. The signaling pathways obtained by KEGG enrichment analysis included calcium signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, relaxin signaling pathway, Serotonergic synapse signaling pathway. The molecular docking results showed that there were molecular binding sites between the key active ingredients and the core targets with strong binding activity. CONCLUSION Compound Xuanju Capsule may treat ED through multi-target pathways such as anti-inflammatory and improving cellular oxidative stress.
Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/drug therapy* ; Molecular Docking Simulation ; Male ; Humans ; Signal Transduction ; Protein Interaction Maps ; Network Pharmacology ; Capsules ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.