Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

[Contamination Characteristics and Ecological Risk of Antibiotics in Contaminated Sites of Typical Pharmaceutical Factories in China].

To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plants， samples of the surface soil， soil column， wastewater treatment process water， ground water， and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samples， and the maximum concentrations at each sampling point in the surface soil， soil column， residue dregs， wastewater treatment process water， and groundwater were 420 ng·g-1， 595 ng·g-1， 139 ng·g-1， 1 151 ng·L-1， and 6.65 ng·L-1， respectively. Most of the antibiotics were found in the surface soil， showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazine， sulfaquinoxaline， tetracycline， chlorotetracycline， and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.

Effectiveness of acupuncture combined with artificial tears in managing dry eye syndrome: A systematic review and meta-analysis.

BACKGROUND: Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis. METHODS: A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described. RESULTS: Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = -2.08, 95% CI (-2.96, -1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups. CONCLUSION: The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.

Leech extract alleviates idiopathic pulmonary fibrosis by TGF-ß1/Smad3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear. AIM OF THE STUDY: Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components. MATERIALS AND METHODS: In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3-10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-ß1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays. RESULTS: Using TGF-ß1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis. CONCLUSIONS: Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-ß1/Smad3 signaling pathway.

Treatment of postpartum depression with integrated traditional Chinese and Western medicine nursing and electrical stimulation.

BACKGROUND: Postpartum depression (PPD) is a common psychological disease among puerperal women, and postpartum pelvic floor dysfunction is a common disease among pregnant women. The occurrence of postpartum pelvic floor dysfunction will increase the incidence of PPD. AIM: To explore the therapeutic effect of integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis on PPD. METHODS: From April 2020 to January 2022, 100 parturients with a rectus abdominis muscle separation distance > 2.0 cm who underwent reexamination 6 wk after delivery at our hospital were selected as the research subjects. According to the random number table method, the patients were divided into either an observation group (n = 50) or a control group (n = 50). There was no significant difference in the general data between the two groups (P > 0.05). Both groups were treated by electrical stimulation. The observation group was additionally treated by integrated traditional Chinese and Western medicine nursing. A self-designed Depression Knowledge Questionnaire was used to evaluate the awareness of knowledge on depression in all patients 3 wk after intervention. The Hamilton Depression Scale (HAMD) was used to evaluate the depression before intervention and 1 wk and 3 wk after intervention, and the Morisky Medication Adherence Scale (MMAS-8) was used to evaluate the medication compliance. SPSS19.0 was used for statistical analyses. RESULTS: The rate of awareness of knowledge on depression in the observation group was significantly higher than that of the control group (P < 0.05). The scores of MMAS-8 were comparable between the two groups before intervention (P > 0.05), but were significantly higher in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). The HAMD scores were comparable between the two groups before intervention (P > 0.05), but were significantly lower in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). CONCLUSION: Integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis is effective in the treatment of postpartum depression and worthy of clinical promotion.

Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1ß (IL-1ß), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/ß (IKKα/ß), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1ß and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION: PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

Enhanced biological phosphorus removal by high concentration powder carrier bio-fluidized bed (HPB): Phosphorus distribution, cyclone separation, and metagenomics.

This study provides a comparative investigation of phosphorus removal between anaerobic-anoxic-oxic (AAO) and high-concentration powder carrier bio-fluidized bed (HPB) in the same full-scale wastewater treatment plant. The results showed that the total phosphorus removal of HPB was 71.45%-96.71%. Compared with AAO, the total phosphorus removal of HPB can be increased by a maximum of 15.73%. The mechanisms of enhanced phosphorus removal by HPB include the followings. Biological phosphorus removal was significant. The anaerobic phosphorus release capacity of HPB was enhanced and polyphosphate (Poly-P) in the excess sludge of HPB was 1.5 times higher than that of AAO. The relative abundance of Candidatus Accumulibacter was 5 times higher than that of AAO, and oxidative phosphorylation and butanoate metabolism were enhanced. The analysis of phosphorus distribution showed that cyclone separation increased the chemical phosphorus precipitation (Chem-P) in the excess sludge by 16.96% to avoid accumulation in the biochemical tank. The phosphorus adsorbed by extracellular polymeric substance (EPS) in the recycled sludge was stripped, and the EPS bound-P in the excess sludge increased by 1.5 times. This study demonstrated the feasibility of HPB to improve the phosphorus removal efficiency for domestic wastewater.

eIF3a sustains non-small cell lung cancer stem cell-like properties by promoting YY1-mediated transcriptional activation of ß-catenin.

Cancer stem cells (CSCs) are the leading cause of recurrence and poor prognosis in non-small cell lung cancer (NSCLC). Eukaryotic translation initiation factor 3a (eIF3a) participates in many tumor development processes, such as metastasis, therapy resistance, and glycolysis, all of which are closely associated with the presence of CSCs. However, whether eIF3a maintains NSCLC-CSC-like properties remains to be elucidated. In this study, eIF3a was highly expressed in lung cancer tissues and was linked to poor prognosis. eIF3a was also highly expressed in CSC-enriched spheres compared with adherent monolayer cells. Moreover, eIF3a is required for NSCLC stem cell-like traits maintenance in vitro and in vivo. Mechanistically, eIF3a activates the Wnt/ß-catenin signaling pathway, promoting the transcription of cancer stem cell markers. Specifically, eIF3a promotes the transcriptional activation of ß-catenin and mediates its nuclear accumulation to form a complex with T cell factor 4 (TCF4). However, eIF3a has no significant effect on protein stability and translation. Proteomics analysis revealed that the candidate transcription factor, Yin Yang 1 (YY1), mediates the activated effect of eIF3a on ß-catenin. Overall, the findings of this study implied that eIF3a contributes to the maintenance of NSCLC stem cell-like characteristics through the Wnt/ß-catenin pathway. eIF3a is a potential target for the treatment and prognosis of NSCLC.

[Tiaoqi Jieyu acupuncture for treatment-resistant depression: a randomized controlled trial].

OBJECTIVE: To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement. METHODS: A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24+), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed. RESULTS: After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001). CONCLUSION: Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.

Role of L-Arginine on the Expression of Coagulation Factor VIII Gene.

Objective: To explore the key sites in which L-arginine affects the expression of human coagulation factor VIII gene, and to create new drug targets for the treatment of hemophilia. Methods: A total of 5 human FVIII genes (A1, A2, A3, C1 and C2) with B domain deletion were transfected into human umbilical vein endothelial cells (HUVECs) as promoters. Run-on assay and ELISA analysis were performed to observe the driving effect of each domain gene on chloramphenicol acetyl transferase (CAT) gene transcription and expression, and the effect of L-arginine on each promoter. Results: In co-culture with L-arginine, transcriptional expression of the CAT gene was not detected in the PCAT3-Basic group (negative control without promoters), PA3-CAT3-Enhancer group or PC1-CAT3-Enhancer group. The transcriptional expression of CAT gene in the PCAT3-Control group (positive control with promoters) and PA1-CAT3-Enhancer group was unchanged compared with the non-L-arginine intervention, while the transcriptional expression of CAT gene in the PA2-CAT3-Enhancer group was significantly enhanced. Conclusions: A1 and A2 domain genes had promoter function and could initiate the transcription and expression of CAT gene, but A3, C1 and C2 domain genes could not. Moreover, L-arginine can significantly enhance transcription and expression of human coagulation factor VIII via A2 domain.

Tiaoqi Jieyu acupuncture for treatment-resistant depression: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement.@*METHODS@#A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24+), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed.@*RESULTS@#After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001).@*CONCLUSION@#Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.

[Visualization of research in treatment of vascular dementia by CiteSpace].

In light of the tremendous number of patients with vascular dementia in China, it is of great significance for the treatment of this disease to summarize related research focuses. In this study, articles on the treatment of vascular dementia, which were included in CNKI and Web of Science from January 1, 2012 to December 31, 2021, were analyzed. Specifically, CiteSpace 5.7.R2 was employed to visualize nationalities of authors, author affiliations, authors, keywords, and journals, and dissect the status quo and trend of research on the treatment of this disease. On this basis, the research focuses and evolution were elucidated. The findings are expected to serve as reference for the future research. Finally, 2 579 Chinese articles and 453 English articles were included. The annual number of published articles showed an upward trend. Authors from China published most papers and England had the highest centrality value. HU Yue-qiang and LIU Cun-zhi respectively published the most Chinese and English articles. Guangxi University of Chinese Medicine and Capital Medical University respectively topped the author affiliations in the number of published Chinese and English articles. Among the English journals, Anal Biochem and Stroke separately boasted the highest centrality value and the highest cited frequency. The analysis of keywords in the Chinese articles suggested that most studies on the treatment of vascular dementia focused on the observation of patients' mobility after treatment. Moreover, as for the therapeutic method, western medicine, as well as the Chinese medicine and acupuncture frequently attracted the attention of scholars. Basic research highlighted the oxidative stress, angiogenesis, and apoptosis. According to the analysis result of keywords in English articles on treatment of vascular dementia, the focus was the improvement of the memory function of patients with vascular dementia. As to the therapeutic method, drug therapy was frequently studied compared with other methods. The basic research focused on autophagy, nerve regeneration, and oxidative stress. This study concludes that the future research trend might be the combination of Chinese and western medicine in the treatment of vascular dementia.

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification.

Background: Gout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown. Objectives: To explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification. Methods: The ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-κB, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining. Results: 48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, (-)-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1ß, TNF-α, and p38. The data from in vitro experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-κB, and NLRP3 signaling pathways. Conclusion: Our finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-κB, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.

Overexpression of SRD5A3 in Hepatocellular Carcinoma and Its Molecular Mechanism: A Study of Bioinformatics Exploration Analysis with Experimental Verification.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and more prevalent among males than females. However, the biological role of enzyme 5α-reductase (SRD5A3), which plays a critical role in the androgen receptor signaling pathway during HCC development, remains poorly understood. Methods: ONCOMINE, GEPIA, UALCAN, and Kaplan-Meier Plotter were used to analyze the expression and prognostic value of SRD5A3 in HCC. STRING and Metascape were applied to analyze potential target and molecular pathways underlying SRD5A3 in HCC. A real-time quantitative reverse transcription-polymerase chain reaction was used to validate the downstream target expression of SRD5A3. Results: The expression of SRD5A3 was significantly overexpressed in HCC tissues compared with normal tissues, while the expression of SRD5A1 and SRD5A2 were downregulated in multiple public datasets. It may be that the low methylation of the SRD5A3 promoter leads to its overexpression. The level of SRD5A3 tended to be higher expressed in clinical samples with advanced stage and positive node metastasis. Furthermore, the patients with higher SRD5A3 were remarkably associated with poorer overall survival and disease-free survival in the TCGA data. In addition, the increased mRNA expression of SRD5A3 could predict poorer overall survival in Kaplan-Meier Plotter database including different patient cohorts. Moreover, HCC patients with higher level of SRD5A3 had significantly shorter recurrence-free survival, progression-free survival, and disease-specific survival. Furthermore, enrichment analysis demonstrated that multiple processes, such as steroid hormone biosynthesis, lipid biosynthetic process, and androgen metabolic process, were affected by SRD5A1-3 alterations. In vitro experiments showed that the expression of SRD5A3 was increased in HCC tissues than that in adjacent tissues. SRD5A3 silencing promoted the expression of DOLK in two HCC cell lines. Conclusions: This study identified SRD5A3/DOLK as a novel axis to regulate HCC development.

Efficacy and Safety of Gegen Qinlian Decoction for Pediatric Diarrhea: A Systematic Review and Meta-Analysis.

Objective: To evaluate the clinical efficacy and safety of Gegen Qinlian decoction in the treatment of pediatric diarrhea. Methods: A search for relevant RCTs was performed from which a systematic review and meta-analysis was conducted. This meta-analysis was registered at INPLASY (reference number ID: INPLASY202180105). Results: (1) Eleven trials involving 1126 patients were included in the meta-analysis. (2) Two trials recorded the adverse events. (3) The meta-analysis showed that compared with the control group, the experimental group has a significantly shorter duration of diarrhea in children (MD = -18.64, 95% CI (-23.76, -13.52), P < 0.00001), duration of fever (MD = -19.43, 95% CI (-25.76, -13.11), P < 0.00001), duration of vomiting [MD = -22.51, 95% CI (-29.92, -15.09), P < 0.00001], duration of correcting dehydration (MD = -23.35, 95% CI (-35.48, -11.22), P=0.0002), and the effective rate (OR = 4.64, 95% CI (3.12, 6.90), P < 0.00001). Conclusion: There were significant differences in the clinical efficacy in the treatment of pediatric diarrhea between the experimental and control groups. Thus, Gegen Qinlian decoction may have certain advantages in the treatment of pediatric diarrhea. In addition, we conclude the following: (1) the application of Gegen Qinlian decoction to treat this disease is recommended for >5 days. (2) We recommend conducting multicenter RCTs to avoid the impact of regional differences on the results. (3) We recommend using the unmodified Gegen Qinlian decoction, which may have better efficacy.

Isoschaftoside Reverses Nonalcoholic Fatty Liver Disease via Activating Autophagy In Vivo and In Vitro.

Nonalcoholic fatty liver disease (NAFLD) is the most common metabolic liver disease globally, and the incidence of NAFLD has been increasing rapidly year by year. Currently, there is no effective pharmacotherapy for NAFLD. Therefore, studies are urgently needed to explore therapeutic drugs for NAFLD. In this study, we show that isoschaftoside (ISO) dramatically reduces lipid deposition in cells. Meanwhile, ISO treatment reverses the NAFLD and reduces hepatic steatosis in mice. Importantly, we reveal that ISO suppresses the expression of light-chain 3-II (LC3-II) and SQSTM1/p62 in palmitic acid (PA) induced autophagy inhibition in the cell model and the NAFLD mouse model, which suggests that ISO might reverse NAFLD through regulating autophagy flux. We propose that ISO might alleviate hepatic steatosis in NAFLD via regulating autophagy machinery. Consequently, our study suggests that ISO might be of potential clinical value in the field of NAFLD therapy. ISO might have the potential for future therapeutic application.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats.

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs). METHODS: Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta. RESULTS: EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects. CONCLUSION: EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Efficacy and safety of electroacupuncture for post-stroke depression: a randomized controlled trial.

OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of electroacupuncture (EA) treatment for post-stroke depression (PSD). METHODS: This study was a single-center, single-blinded, parallel-arm randomized controlled trial. In total, 65 patients with PSD were randomly allocated into EA and sham EA groups. Treatment was administered at GV20, Sishencong, SP6, LR3 and BL18 in both groups. The EA group received EA treatment, while the sham EA group received sham EA treatment using the Park device. Treatment was given three times a week for 4 weeks. The primary outcome was the Hamilton Rating Scale for Depression (HRSD). Secondary outcomes included the Zung Self-Rating Depression Scale (SDS), National Institutes of Health Stroke Scale (NIHSS), Barthel Daily Living Index (BI) and depression scale of traditional Chinese medicine (TCM). Primary and secondary outcomes were assessed at baseline, week 2 after treatment, week 4 after treatment and week 8 of follow-up. Safety assessment was conducted at each visit for 4 weeks of treatment. RESULTS: Significant differences in HRSD, SDS, NIHSS, BI and TCM scale scores were found in the EA group before and after acupuncture treatment (all p < 0.001). Compared with the sham EA group, HRSD scores improved significantly in the EA group at the end of week 2 (F = 31.33, p < 0.001), week 4 (F = 35.58, p < 0.001) and week 8 after treatment onset (F = 25.03, p < 0.001). Similarly, significant improvements were observed in SDS, NIHSS and BI scores. Two participants in the EA group suffered a local hematoma, while no adverse events were reported in the sham EA group. CONCLUSION: EA appears to be an efficacious and safe treatment for PSD. According to our results, EA may alleviate depressive symptoms, and improve neurological function and capabilities with respect to activities of daily living (ADLs). TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17012610 (Chinese Clinical Trial Registry).

Evaluation of potential feedstock for biogas production via anaerobic digestion in Malaysia: kinetic studies and economics analysis.

As the population increases, energy demands continue to rise rapidly. In order to satisfy this increasing energy demand, biogas offers a potential alternative. Biogas is economically viable to be produced through anaerobic digestion (AD) from various biomass feedstocks that are readily available in Malaysia, such as food waste (FW), palm oil mill effluent (POME), garden waste (GW), landfill, sewage sludge (SS) and animal manure. This paper aims to determine the potential feedstocks for biogas production via AD based on their characteristics, methane yield, kinetic studies and economic analysis. POME and FW show the highest methane yield with biogas yields up to 0.50 L/g VS while the lowest is 0.12 L/g VS by landfill leachate. Kinetic study shows that modified Gompertz model fits most of the feedstock with R 2 up to 1 indicating that this model can be used for estimating treatment efficiencies of full-scale reactors and performing scale-up analysis. The economic analysis shows that POME has the shortest payback period (PBP), highest internal rate of return (IRR) and net present value (NPV). However, it has already been well explored, with 93% of biogas plants in Malaysia using POME as feedstock. The FW generation rate in Malaysia is approximately 15,000 tonnes per day, at the same time FW as the second place shows potential to have a PBP of 5.4 years and 13.3% IRR, which is close to the results achieved with POME. This makes FW suitable to be used as the feedstock for biogas production.

The quality of reporting of randomized controlled trials of HuatuoZaizao pill for stroke.

Background: HuatuoZaizao pill (HZP), a Chinese patent medicine, is often used in the treatment of stroke. However, there is still a lack of enough evidence to recommend the routine use of HZP for stroke. This study is aimed at evaluating the quality of reporting of randomized controlled trials (RCTs) on HZP for stroke. Methods: RCTs on HuatuoZaizao pill for stroke were evaluated by using Consolidated Standards of Reporting Trials (CONSORT) guidelines and CONSORT extension criteria on reporting herbal interventions (CONSORT-CHM) guidelines. Microsoft Excel 2007 and SPSS20.0 was used for statistics analyses. Results: Seventeen studies involving 1801 stroke patients were identified. CONSORT-CHM has expanded 24.3% (9/37) items in CONSORT and added a small item. The average scores of CONSORT evaluation is 14.6, while the average scores of the CONSORT-CHM evaluation is 11.6. The central items in CONSORT as eligibility criterion, sample size calculation, primary outcome, method of randomization sequence generation, allocation concealment, implementation of randomization, description of blinding, and detailed statistical methods were reported in 77%, 6%, 100%, 47%, 6%, 6%, 6%, and 94% of trials, respectively. In terms of the CONSORT-CHM, none of the articles reported in detail the dosage form, origin, formula basis and so on of HZP, and only half of studies reported the outcome indicators related to Traditional Chinese Medicine syndromes. Conclusion: The overall report quality of RCT related to HZP is low. HZP still needs to report higher quality RCTs to prove its effectiveness and safety.