Electroacupuncture and Growth Hormone for Pain Management Post-Quadriceps Ligament Reconstruction: A Prospective Study.

Objective: This study aimed to investigate the efficacy of electroacupuncture (EA) combined with growth hormone in alleviating pain and enhancing knee function following quadriceps ligament reconstruction. Methods: A prospective study was conducted, and a total of 90 patients exhibiting quadriceps atrophy after anterior cruciate ligament reconstruction were recruited between July 2020 and July 2022 from Shenzhen Pingle Orthopedic Hospital. They were randomly assigned to either the control group or the observation group , with 45 patients in each. The control group received routine rehabilitation training along with growth hormone treatment, while the observation group received routine rehabilitation training in addition to EA and growth hormone treatment. The study assessed the visual analogue score (VAS) for postoperative pain, knee function, and clinical outcomes in both groups. Results: The total effective rate in the observation group was significantly higher compared to the control group, with a statistically significant difference (P < .05). Initially, there were no significant differences between the two groups in peri-thigh atrophy index, VAS score, Lysholm score, knee swelling, knee stability, and range of motion (ROM) score (P > .05). However, after 3 and 6 months of treatment, significant reductions were observed in peri-thigh atrophy index, VAS score, knee swelling, and ROM score in the observation group compared to the control group (P < .05). Moreover, Lysholm score and knee stability significantly increased in the observation group (P < .05), with changes significantly higher than those in the control group (P < .05). Conclusions: EA combined with growth hormone treatment significantly improves postoperative pain and knee joint function in patients undergoing quadriceps ligament reconstruction. This combination therapy holds promise for enhancing rehabilitation outcomes in this patient population.

Rational modification of melatonin for broad-spectrum antifungal agents discovery.

Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.

Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway.

BACKGROUND: Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain. AIM: To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism. METHODS: Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA. RESULTS: In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1ß induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002. CONCLUSION: This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Dexmedetomidine ameliorates high glucose-induced epithelial-mesenchymal transformation in HK-2 cells through the Cdk5/Drp1/ROS pathway.

Epithelial-mesenchymal transformation (EMT) plays an important role in the progression of diabetic nephropathy. Dexmedetomidine (DEX) has shown renoprotective effects against ischemic reperfusion injury; however, whether and how DEX prevents high glucose-induced EMT in renal tubular epithelial cells is incompletely known. Here, we conduct in vitro experiments using HK-2 cells, a human tubular epithelial cell line. Our results demonstrate that high glucose increases the expressions of EMT-related proteins, including Vimentin, Slug, Snail and Twist, while decreasing the expression of E-cadherin and increasing Cdk5 expression in HK-2 cells. Both Cdk5 knockdown and inhibition by roscovitine increase the expressions of E-cadherin while decreasing the expressions of other EMT-related markers. DEX inhibits Cdk5 expression without affecting cell viability and changes the expressions of EMT-related markers, similar to effects of Cdk5 inhibition. Furthermore, Cdk5 is found to interact with Drp1 at the protein level and mediate the phosphorylation of Drp1. In addition, Drp1 inhibition with mdivi-1 could also restrain the high glucose-induced EMT process in HK-2 cells. Immunofluorescence results show that roscovitine, Mdivi-1 and DEX inhibit high glucose-induced intracellular ROS accumulation, while the oxidant H 2O 2 eliminates the protective effect of DEX on the EMT process. These results indicate that DEX mitigates high glucose-induced EMT progression in HK-2 cells via inhibition of the Cdk5/Drp1/ROS pathway.

Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.

Introduction: Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary. Methods: This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes. Discussion: To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

Effects of Niaoduqing granules on inflammatory response of diabetic kidney disease: A meta­analysis.

Diabetic kidney disease (DKD) is one of the most severe chronic microvascular complications of diabetes and the leading cause of end-stage kidney disease worldwide. The mechanism of inflammation underlying DKD has been attracting attention over recent years, but effective therapeutic strategies have remained elusive. Niaoduqing (NDQ) granules are one of the most commonly used drugs for the treatment of DKD in China, and it has therapeutic effects against inflammation in DKD. Therefore, the aim of the present analysis was to evaluate the inflammatory response outcomes and safety of NDQ granules for the treatment of DKD. The following databases were searched from their inception to 31st of May 2023 to obtain published accounts of relevant randomized controlled trials: China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, The Chinese Biomedicine, PubMed, Web of Science and Cochrane Library. The 'risk of bias' evaluation tool produced by the Cochrane Collaboration Handbook was used for evaluating the quality, whereas Revman software (version 5.3) was used for meta-analysis. In total, 16 studies were included into the present study according to criteria, with a total of 1,526 patients. Compared with those in the control group, the results of the meta-analysis revealed that the combination of conventional treatment and NDQ granules may further decrease C-reactive protein [standardized mean difference (SMD), -1.33; 95% confidence interval (CI), -1.76, -0.91; P<0.00001], TNF-α (SMD, -1.90; 95% CI, -2.35,-1.45; P<0.00001) and IL-6 (SMD, -1.72; 95% CI, -2.52,-0.91; P<0.0001) levels, whilst increasing the clinical effective rate (risk ratio, 1.22; 95% CI, 1.14,1.29; P<0.00001), in patients with DKD. In terms of safety, a total of 34 and 39 patients included in the intervention and in the control group, respectively, developed adverse reactions. Results from the present analysis suggest that NDQ granules may be beneficial in suppressing inflammation caused by DKD when used in combination with conventional treatment, potentially guiding future directions in clinical practice. However, further high-quality studies are needed to confirm the anti-inflammation response in the future.

Loss of PMFBP1 Disturbs Mouse Spermatogenesis by Downregulating HDAC3 Expression.

PURPOSE: Polyamine modulating factor 1 binding protein (PMFBP1) acts as a scaffold protein for the maintenance of sperm structure. The aim of this study was further to identify the new role and molecular mechanism of PMFBP1 during mouse spermatogenesis. METHODS AND RESULTS: We identified a profile of proteins interacting with PMFBP1 by immunoprecipitation combined with mass spectrometry and demonstrated that class I histone deacetylases, particularly HDAC3 and chaperonin-containing TCP1 subunit 3 (CCT3), were potential interaction partners of PMFBP1 based on network analysis of protein-protein interactions and co-immunoprecipitation. Immunoblotting and immunochemistry assays showed that loss of Pmfbp1 would result in a decline in HDACs and change the proteomic profile of mouse testis, in which differently expressed proteins are associated with spermatogenesis and assembly of flagella, which was proved by proteomic analysis of testis tissue obtained from Pmfbp1-/- mice. After integrating with transcriptome data for Hdac3-/- and Sox30-/- round sperm obtained from a public database, RT-qPCR confirmed ring finger protein 151 (Rnf151) and ring finger protein 133 (Rnf133) were key downstream response factors of the Pmfbp1-Hdac axis affecting mouse spermatogenesis. CONCLUSION: Taken together, this study indicates a previously unidentified molecular mechanism of PMFBP1 in spermatogenesis whereby PMFBP1 interacts with CCT3, affecting the expression of HDAC3, followed by the downregulation of RNF151 and RNF133, resulting in an abnormal phenotype of sperm beyond the headless sperm tails. These findings not only advance our understanding of the function of Pmfbp1 in mouse spermatogenesis but also provide a typical case for multi-omics analysis used in the functional annotation of specific genes.

Huobahuagen tablet improves renal function in diabetic kidney disease: a real-world retrospective cohort study.

Objective: We aimed to explore the value of Huobahuagen tablet (HBT) in improving decreased renal function for patients with diabetic kidney disease (DKD) over time. Methods: This was a single-center, retrospective, real-world study on eligible 122 DKD patients who continued to use HBT + Huangkui capsule (HKC) therapy or HKC therapy without interruption or alteration in Jiangsu Province Hospital of Chinese Medicine from July 2016 to March 2022. The primary observation outcomes included estimated glomerular filtration rate (eGFR) at baseline and 1-, 3-, 6-, 9-, and 12-month follow-up visits and changes in eGFR from baseline (ΔeGFR). Propensity score (PS) and inverse probability treatment weighting (IPTW) were used to control for confounders. Results: eGFR was significantly higher in the HBT + HKC group than in the HKC alone group at the 6-, 9-, and 12-month follow-up visits (p = 0.0448, 0.0002, and 0.0037, respectively), indicating the superiority of HBT + HKC over HBT alone. Furthermore, the ΔeGFR of the HBT + HKC group was significantly higher than that of the HKC alone group at the 6- and 12-month follow-up visits (p = 0.0369 and 0.0267, respectively). In the DKD G4 patients, eGFR was higher in the HBT + HKC group at the 1-, 3-, 6-, 9-, and 12-month follow-up visits compared with baseline, with statistically significant differences at the 1-, 3-, and 6- month follow-up visits (p = 0.0256, 0.0069, and 0.0252, respectively). The fluctuations in ΔeGFR ranged from 2.54 ± 4.34 to 5.01 ± 5.55 ml/min/1.73 m2. Change in the urinary albumin/creatinine ratio from baseline did not exhibit a significant difference between the two groups at any of the follow-up visits (p > 0.05 for all). Adverse event incidence was low in both groups. Conclusion: The findings of this study based on real-world clinical practice indicate that HBT + HKC therapy exhibited better efficacy in improving and protecting renal function with a favorable safety profile than HKC therapy alone. However, further large-scale prospective randomized controlled trials are warranted to confirm these results.

Effects of SGLT2 inhibitors on hepatic fibrosis and steatosis: A systematic review and meta-analysis.

Objective: Clinical trials have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) are closely associated with hepatic fibrosis and steatosis by FibroScan. This paper aimed at evaluating the effects of SGLT2i on hepatic fibrosis and steatosis, which are presented as liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, and Wanfang Database were searched for randomized clinical trials from database establishment to 30 November 2022 with no language restrictions. The risk of bias was evaluated by Collaboration Handbook. Software Stata 17 and Review Manager (version 5.3) were used for meta-analysis. Results: A total of eight articles including 686 patients were included. Compared with the control group, our results showed that SGLT2i could lower levels of LSM [MD = -0.82, 95%CI (-1.38, -0.25), p = 0.005] and CAP [MD = -12.80, 95%CI (-20.57, -5.03), p = 0.001]. Further subgroup analyses indicated that SGLT2i presented more advantages on longer treatment duration and more serious steatosis in decreasing LSM. For CAP, SGLT2i exhibited a clear advantage in subgroup analyses of longer treatment duration, younger people, dapagliflozin, worse fibrosis, and steatosis. Conclusion: SGLT2i could reduce LSM and CAP in contrast to other antihyperglycemic drugs. However, the included studies are not definitive, and well-designed, more multi-centered, blinded randomized clinical trials are warranted to definitively establish reliable evidence.

Insect kinin mimics act as potential control agents for aphids: Structural modifications of Trp4.

Insect kinins are endogenous, biologically active peptides with various physiological functions. The use of insect kinins in plant protection is being evaluated by many groups. Some kinins have been chosen as lead compounds for pest control. We previously reported an insect kinin mimic IV-3 that had insecticidal activity. And by introducing a strong electron withdrawing group (-CF3 ) on the benzene ring (Phe2 ), we discovered a compound, L7 , with better activity than lead IV-3. In this work, taking L7 as the lead compound, we designed and synthesized 13 compounds to evaluate the influence of position 4 (Trp4 ) of insect kinin on insecticidal activity, by replacing the H atom on tryptophan with -CH3 and -Cl or substituting the indole ring of tryptophan with the benzene, naphthalene, pyridine, imidazole, cyclohexane, and alkyl carboxamides. The aphid bioassay results showed that the compounds M1 , M3 , and M5 were more active than the positive control, pymetrozine. Especially, replacing the side chain by an indole ring with 4-Cl substitution (M1 , LC50 = 0.0029 mmol/L) increased the aphicidal activity. The structure-activity relationships (SARs) indicated that the side chain benzene ring at this position may be important to the aphicidal activity. In addition, the toxicity prediction by Toxtree, and the toxicity experiments on Apis mellifera suggested that M1 was no toxicity risk on a non-target organism. It could be used as a selective and bee-friendly insecticide to control aphids.

Melatonin functions as a broad-spectrum antifungal by targeting a conserved pathogen protein kinase.

Melatonin is a low-cost natural small indole molecule with versatile biological functions. However, melatonin's fungicidal potential has not been fully exploited, and the mechanism remains elusive. Here, we report that melatonin broadly inhibited 13 plant pathogens. In the rice blast fungal pathogen Magnaporthe oryzae, melatonin inhibited fungal growth, formation of infection-specific structures named appressoria, and plant infection, reducing disease severity. Melatonin entered fungal cells efficiently and colocalized with the critical mitogen-activated protein kinase named Mps1, suppressing phosphorylation of Mps1. Melatonin's affinity for Mps1 via two hydrogen bonds was demonstrated using surface plasmon resonance and chemical modifications. To improve melatonin's efficiency, we obtained 20 melatonin derivatives. Tert-butyloxycarbonyl melatonin showed a 25-fold increase in fungicidal activities, demonstrating the feasibility of chemical modifications in melatonin modification. Our study demonstrated the broad-spectrum fungicidal effect of melatonin by suppressing Mps1 as one of the targets. Through further systematic modifications, developing an eco-friendly melatonin derivative of commercial values for agricultural applications appears promising.

Quality in balance sensitivity through martial arts applied to children / Qualidade na sensibilidade do equilíbrio pelas artes marciais aplicadas às crianças / Calidad en la sensibilidad del equilibrio a través de las artes marciales aplicadas a los niños

ABSTRACT Introduction: Martial arts training focuses on science, methodology, and practice. Martial arts are a symbol of physical fitness. The academic analysis of the influence of martial arts training on children's physical health is of great importance for promoting traditional Chinese culture. It can enrich sports intervention programs to improve children's physical health. Objective: Analyze the effect of sensory quality training on martial arts balance training in children. Methods: Children aged 8 to 12 years were selected as research subjects. After repeated deliberations, a children's martial arts set was designed and implemented. The pilot project analyzes the importance of sensory quality in the essential stage of children's martial arts training. Results: After the experiment, there was a significant difference in balance quality in the experimental group (p<0.01). After the experiment, the difference in balance sense between the experimental and control groups was significant (p<0.01). Conclusion: In the basic training phase of children's martial arts, coaches should require athletes to master basic martial arts skills more comprehensively. All movement combinations in martial arts require comprehensive physical fitness and balance sensitivity, including speed, flexibility, and coordination. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento em artes marciais concentra-se na ciência, na metodologia e na prática. As artes marciais são um símbolo de aptidão física. A análise acadêmica da influência do treinamento de artes marciais na saúde física das crianças é de grande importância para a promoção da cultura tradicional chinesa e pode enriquecer os programas de intervenção esportiva para melhorar a saúde física infantil. Objetivo: Analisar o efeito do treinamento de qualidade sensitiva no treinamento de equilíbrio das artes marciais em crianças. Métodos: Selecionou-se crianças de 8 a 12 anos como objetos de pesquisa. Após repetidas deliberações, foi elaborado e implementado um conjunto de artes marciais infantis. O projeto piloto analisa a importância da qualidade sensitiva na etapa essencial do treinamento das artes marciais infantis. Resultados: Após o experimento, houve uma diferença significativa na qualidade do equilíbrio no grupo experimental (p<0,01). Após o experimento, a diferença no sentido de equilíbrio entre os grupos experimental e de controle foi significativa (p<0,01). Conclusão: Na fase de treinamento básico das artes marciais infantis, os treinadores devem exigir que os atletas dominem as habilidades básicas das artes marciais de forma mais abrangente. Todas as combinações de movimentos nas artes marciais exigem aptidão física e sensibilidade de equilíbrio abrangentes, incluindo velocidade, flexibilidade e coordenação. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento de las artes marciales se centra en la ciencia, la metodología y la práctica. Las artes marciales son un símbolo de la condición física. El análisis académico de la influencia del entrenamiento de artes marciales en la salud física de los niños es de gran importancia para la promoción de la cultura tradicional china y puede enriquecer los programas de intervención deportiva para mejorar la salud física de los niños. Objetivo: Analizar el efecto del entrenamiento de la calidad sensorial en el entrenamiento del equilibrio en artes marciales en niños. Métodos: Se seleccionaron niños de 8 a 12 años como sujetos de la investigación. Tras repetidas deliberaciones, se diseñó y puso en marcha un conjunto de artes marciales para niños. El proyecto piloto analiza la importancia de la calidad sensorial en la etapa esencial del entrenamiento de artes marciales de los niños. Resultados: Después del experimento, hubo una diferencia significativa en la calidad del equilibrio en el grupo experimental (p<0,01). Tras el experimento, la diferencia en el sentido del equilibrio entre los grupos experimental y de control fue significativa (p<0,01). Conclusión: En la fase de formación básica de las artes marciales infantiles, los entrenadores deberían exigir a los deportistas un dominio más completo de las habilidades marciales básicas. Todas las combinaciones de movimientos en las artes marciales requieren una amplia aptitud física y sensibilidad al equilibrio, incluidas la velocidad, la flexibilidad y la coordinación. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Efficacy and safety of Abelmoschus moschatus capsules combined with tripterygium glycoside tablets on diabetic nephropathy: A systematic review and meta-analysis.

Background: Diabetic nephropathy (DN) is one of the most serious chronic micro-vascular complications of diabetes and the leading cause of end-stage kidney disease (ESRD) worldwide, with reduced expectancy and quality of life and colossal financial and social burden worldwide. In spite of emerging treatments on DN, effective therapy on delaying the progression of DN is still lacking. In clinical practice, there are many studies focusing on Abelmoschus moschatus (AM) capsules together with Tripterygium glycoside (TG) tablets in the treatment of DN, and excellent results have been obtained. Objective: The study aimed to evaluate the efficacy and safety of AM combined with TG in the treatment of DN. Methods: Databases including PubMed, Web of Science, Cochrane Library, Embase, CNKI, WF, and VIP were searched from their inception to 1 March 2022. The "risk of bias" evaluation tool produced by the Cochrane Collaboration Handbook was used for evaluating the quality of the included studies. Revman 5.3 software was used for meta-analysis. Results: Here, 11 studies with a total of 1,072 participants were included for this meta-analysis. Our results showed that AM combined with TG plus basic treatment could lower levels of 24 h-UP [MD = -0.18; 95% CI: (-0.21, -0.14); p < 0.00001], Scr [MD = -15.29; 95% CI: (-28.69, -1.88); p = 0.03], and BUN [MD = -1.18; 95% CI: (-1.69, -0.68); p < 0.00001]. Meanwhile, the adverse reaction rate increased in the combination group [RR = 1.88; 95% CI (1.26, 2.82); p = 0.002]. Conclusion: Current evidence suggests that AM combined with TG may be more effective in the treatment of DN, which will be highly beneficial to further theoretical discussion and practical clinical applications. However, the safety cannot be ignored because of nearly increasing 2-fold adverse events, although they can be mitigated through systematic treatment. Meanwhile, due to low quality of the included studies, great possibility of publication bias, and large heterogeneity among different studies, the results of our review should be evaluated with more prudence and high-quality RCTs are warranted to confirm this in the future. Systematic review Registration: www.crd.york.ac.uk, identifier CRD42022344359.

Differences in structural connectivity between diabetic and psychological erectile dysfunction revealed by network-based statistic: A diffusion tensor imaging study.

Introduction: Type 2 diabetes mellitus (T2DM) has been found to be associated with abnormalities of the central and peripheral vascular nervous system, which were considered to be involved in the development of cognitive impairments and erectile dysfunction (ED). In addition, altered brain function and structure were identified in patients with ED, especially psychological ED (pED). However, the similarities and the differences of the central neural mechanisms underlying pED and T2DM with ED (DM-ED) remained unclear. Methods: Diffusion tensor imaging data were acquired from 30 T2DM, 32 ED, and 31 DM-ED patients and 47 healthy controls (HCs). Then, whole-brain structural networks were constructed, which were mapped by connectivity matrices (90 × 90) representing the white matter between 90 brain regions parcellated by the anatomical automatic labeling template. Finally, the method of network-based statistic (NBS) was applied to assess the group differences of the structural connectivity. Results: Our NBS analysis demonstrated three subnetworks with reduced structural connectivity in DM, pED, and DM-ED patients when compared to HCs, which were predominantly located in the prefrontal and subcortical areas. Compared with DM patients, DM-ED patients had an impaired subnetwork with increased structural connectivity, which were primarily located in the parietal regions. Compared with pED patients, an altered subnetwork with increased structural connectivity was identified in DM-ED patients, which were mainly located in the prefrontal and cingulate areas. Conclusion: These findings highlighted that the reduced structural connections in the prefrontal and subcortical areas were similar mechanisms to those associated with pED and DM-ED. However, different connectivity patterns were found between pED and DM-ED, and the increased connectivity in the frontal-parietal network might be due to the compensation mechanisms that were devoted to improving erectile function.

ZLN005 Alleviates In Vivo and In Vitro Renal Fibrosis via PGC-1α-Mediated Mitochondrial Homeostasis.

Currently, chronic kidney disease (CKD) is one of the most common diseases; it is also a serious threat to human health due to its high mortality, and its treatment is still a major clinical challenge. Mitochondrial dyshomeostasis plays an important role in the development of CKD. ZLN005 is a novel peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) activator from our laboratory. To explore whether ZLN005 can protect against CKD in vivo and in vitro, a unilateral ureteral obstruction (UUO) model and TGF-ß1-treated renal tubular epithelial cells (TECs), respectively, were used in this study. We found that ZLN005-administrated UUO mice showed less kidney damages than control mice, as indicated by the reduced expression of fibrotic biomarkers in the kidney of UUO mice. ZLN005 treatment also alleviated the TGF-ß1-induced fibrotic phenotype and lipid accumulation in TECs. Our study demonstrated ZLN005 treatment improved mitochondrial homeostasis at least partially via the activation of PGC-1α, thus maintaining mitochondria function and energy homeostasis. In summary, ZLN005 treatment ameliorates UUO-induced renal fibrosis, providing conceptional support for mitochondria-targeting therapies for chronic kidney disease.

A novel bee-friendly peptidomimetic insecticide: Synthesis, aphicidal activity and 3D-QSAR study of insect kinin analogs at Phe2 modification.

BACKGROUND: As one of the most abundant and destructive pests in agriculture, aphids cause significant damage to crops due to their sap-taking and as virus vectors. Chemical insecticides are the most effective method to control aphids, but they bring insecticide resistance problems and harm nontarget organisms, especially bees, therefore the search for novel eco-friendly aphid control agents with low bee toxicity is urgent. Insect kinins are a class of small neuropeptides that control important functions in insects. In our previous study, we found insect kinin analog IV-3 has good aphicidal activity and the location of the aromatic ring on the side chain of Phe2 is the key to the formation of the ß-turn resulting in the biological activity of insect kinin analogs. However, there are few studies on insect kinin Phe2 substitution and modification, and its structure-activity relationship is still unclear. RESULTS: In this project, 44 insect kinin analogs with the Phe2 modification, replacing it with different natural or unnatural amino acids, were designed and synthesized based on the lead IV-3 to explore the role of the Phe2 residues. Bioassays with soybean aphids of Aphis glycines indicated that nine analogs have better aphicidal activity than the lead IV-3. In particular, compound L25 exhibits excellent aphicidal activity (LC50  = 0.0047 mmol L-1 ) and has low toxicity to bees. Furthermore, a reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) was established to produce a helpful clue that introducing hydrophobic groups away from the backbone chain is beneficial to improve aphicidal activity. CONCLUSION: The residue Phe2 of insect kinin analogs is the key position and has a significant impact on the activity. L25 has a high toxicity for aphids, while a low toxicity to bees, and therefore can be considered as a lead compound to develop new biosafe aphid control agents. Finally, we provide a useful 3D-QSAR model as theoretical guidance for further structural optimization. © 2022 Society of Chemical Industry.

Preclinical evidence of the effect of quercetin on diabetic nephropathy: A meta-analysis of animal studies.

Quercetin, which is present in numerous fruits and vegetables, has shown promise in improving inflammation, lipid profiles, and blood pressure in humans. However, the efficacy of quercetin in diabetic nephropathy (DN) remains preclinical and unclear. Therefore, a meta-analysis based on preclinical animal data is needed to assess the efficacy, optimal dosage, and underlying mechanism of DN treatment to accelerate new drug research and clinical translation. We conducted a literature search in PubMed, Embase, Web of Science, and Cochrane Library to retrieve randomized controlled trials evaluating the effects of quercetin in rat or mouse diabetic models. We assessed the quality of the studies individually according to SYRCLE's risk of bias tool for animal studies. Twenty animal studies, including 378 animals, were included in the meta-analysis. Meta-analysis data showed that renal function indices, such as renal index, urine protein, uric acid, urine albumin, and serum creatinine levels, significantly improved with quercetin administration. However, no significant association was observed between quercetin and creatinine clearance. Quercetin remarkably alleviated oxidative stress by reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and catalase (CAT) activities. In addition, quercetin exhibits anti-inflammatory activity by reducing tumor necrosis factor-α（TNF-α）and interleukin-1ß（IL-1ß）levels. Subgroup analysis performed using quercetin doses and animal species indicated that animal species were a source of heterogeneity. This meta-analysis suggests that quercetin is a promising drug for DN treatment, facilitating clinical prediction and therapy.

A novel homozygous missense mutation in AK7 causes multiple morphological anomalies of the flagella and oligoasthenoteratozoospermia.

PURPOSE: To identify the genetic causes of multiple morphological anomalies of the flagella (MMAF) and oligoasthenoteratozoospermia (OAT). METHODS: Whole-exome sequencing (WES) was performed on the proband to identify pathogenic mutation for infertility. Western blotting and immunofluorescence analysis detected the expression level and localization of adenylate kinase 7 (AK7). RESULTS: We identified a novel homozygous missense mutation (NM_152327: c.1846G > A; p.E616K) in AK7 in two brothers with MMAF and OAT from a consanguineous family by WES. Western blotting and immunofluorescence experiments determined that the expression level of AK7 decreased in the sperm from the proband. The proband and his wife underwent two cycles of intracytoplasmic sperm injection (ICSI) treatment but got unfavorable outcomes. CONCLUSION: This study could provide precise genetic diagnosis for the patient and expand the spectrum of AK7 mutations.

Inhibition or Deletion of Hydroxylases-Prolyl-4-Hydroxyases 3 Alleviates Lipopolysaccharide-induced Neuroinflammation and Neurobehavioral Deficiency.

It is well known that neuroinflammation plays a key role in neurodegenerative diseases. Hypoxia-inducible factor (HIF) and its hydroxylases-Prolyl-4-hydroxyases (PHDs) have been found to modulate the inflammatory processes. Here, the effects of PHDs enzyme onlipopolysaccharide-induced neuroinflammation and neurocognitive deficits were investigated. BV2 microglia cells were stimulated by LPS (1 µg/ml) as neuroinflammation model in vitro. Dimethyloxalylglycine (DMOG, 100 µM) and PHD3-siRNA were used to suppress the expression of PHD3. In vivo, mice received consecutive intraperitoneal injection of LPS (500 µg/kg) for 7 days, and intraperitoneal injection of DMOG (100 mg/kg) was applied 1 h before LPS at the same days. Several neurobehavioral tests (Open field, Novel object recognition and Morris water maze) were used to measure cognitive function. RT-qPCR and Western blotting were used to investigate the expression of inflammatory cytokines, HIF-PHDs protein. Metabolic reprogramming was measured by seahorse method. The results revealed that LPS induced neuroinflammation and PHD3 expression in vivo and vitro. DMOG and PHD3knockout decreased expression of inflammatory cytokines and improved the metabolic reprogramming caused by LPS treatment. Furthermore, pretreatment of DMOG reversed learning and memory deficits in systemic LPS-exposed mice through anti-neuroinflammation, which is independent of DMOG angiogenesis. These findings suggested that PHD3 may mediate LPS-induced microglial activation and neuroinflammation-associated neurobehavioral deficits.