Terminalia bellirica (Gaertn.) Roxb. Extracts reshape the perifollicular microenvironment and regulate the MAPK pathway for androgenetic alopecia treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia bellirica (Gaertn.) Roxb. (TBR), a popular herbal remedy in India and Southeast Asia, has been demonstrated to possess multiple pharmacological activities. However, systematic studies on the medicinal effects and mechanism of TBR for the androgenetic alopecia (AGA) treatment are deficient. MATERIALS AND METHODS: Human Umbilical Vein Endothelial Cells (HUVECs) and testosterone-induced AGA mice were used to evaluate the hair regrowth activity of TBR extracts. Chemical constituents and potential active components of TBR extracts were analyed by UPLC-Q-TOF-MS in vitro/vivo. The hair regrowth mechanisms of TBR were elucidated through network pharmacology and experimental validation. RESULTS: Totally 28 chemical constituents in TBR were identified, of which 15 were predicted as potential active components for AGA therapy. TBR could significantly scavenge ROS, promote VEGF level/cell migration of HUVECs, and inhibiting type II 5α-reductase activity (the inhibit rate: 82.35 ± 1.02 %). Pharmacodynamic evaluation suggested that TBR effectively led to hair regrowth in C57BL6 mice compared to minoxidil. TBR promoted the hair follicle (HF) transition from the telogen phase to anagen phase by decreasing MDA levels, increasing VEFG expression and up-regulating phosphorylated P38/ERK protein levels in the MAPK signalling pathway. CONCLUSIONS: TBR reversed AGA via inhibiting SRD5A2 activity and stimulating the MAPK pathway. Meantime, TBR could remodel the follicle microenvironment by reducing oxidative stress and increasing angiogenesis.

Review on ginseng and its potential active substance G-Rg2 against age-related diseases: Traditional efficacy and mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Shen Nong Herbal Classic, Ginseng (Panax ginseng C.A. Meyer) is documented to possess life-prolonging effects and is extensively utilized in traditional Chinese medicine for the treatment of various ailments such as qi deficiency, temper deficiency, insomnia, and forgetfulness. Ginseng is commonly employed for replenishing qi and nourishing blood, fortifying the body and augmenting immunity; it has demonstrated efficacy in alleviating fatigue, enhancing memory, and retarding aging. Furthermore, it exhibits a notable ameliorative impact on age-related conditions including cardiovascular diseases and neurodegenerative disorders. One of its active constituents - ginsenoside Rg2 (G-Rg2) - exhibits potential therapeutic efficacy in addressing these ailments. AIM OF THE REVIEW: The aim of this review is to explore the traditional efficacy of ginseng in anti-aging diseases and the modern pharmacological mechanism of its potential active substance G-Rg2, in order to provide strong theoretical support for further elucidating the mechanism of its anti-aging effect. METHODS: This review provides a comprehensive analysis of the traditional efficacy of ginseng and the potential mechanisms underlying the anti-age-related disease properties of G-Rg2, based on an extensive literature review up to March 12, 2024, from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar databases. Potential anti-aging mechanisms of G-Rg2 were predicted using network pharmacology and molecular docking analysis techniques. RESULTS: In traditional Chinese medicine theory, ginseng has been shown to improve aging-related diseases with a variety of effects, including tonifying qi, strengthening the spleen and stomach, nourishing yin, regulating yin and yang, as well as calming the mind. Its potential active ingredient G-Rg2 has demonstrated significant therapeutic potential in age-related diseases, especially central nervous system and cardiovascular diseases. G-Rg2 exhibited a variety of pharmacological activities, including anti-apoptotic, anti-inflammatory and antioxidant effects. Meanwhile, the network pharmacological analyses and molecular docking results were consistent with the existing literature review, further validating the potential efficacy of G-Rg2 as an anti-aging agent. CONCLUSION: The review firstly explores the ameliorative effects of ginseng on a wide range of age-related diseases based on TCM theories. Secondly, the article focuses on the remarkable significance and value demonstrated by G-Rg2 in age-related cardiovascular and neurodegenerative diseases. Consequently, G-Rg2 has broad prospects for development in intervening in aging and treating age-related health problems.

Mild near-infrared laser-triggered photo-immunotherapy potentiates immune checkpoint blockade via an all-in-one theranostic nanoplatform.

One of the primary challenges for immune checkpoint blockade (ICB)-based therapy is the limited infiltration of T lymphocytes (T cells) into tumors, often referred to as immunologically "cold" tumors. A promising strategy to enhance the anti-tumor efficacy of ICB is to increase antigen exposure, thereby enhancing T cell activation and converting "cold" tumors into "hot" ones. Herein, we present an innovative all-in-one therapeutic nanoplatform to realize local mild photothermal- and photodynamic-triggered antigen exposure, thereby improving the anti-tumor efficacy of ICB. This nanoplatform involves conjugating programmed death-ligand 1 antibody (aPD-L1) with gadolinium-doped near-infrared (NIR)-emitting carbon dots (aPD-L1@GdCDs), which displays negligible cytotoxicity in the absence of light. But under controlled NIR laser irradiation, the GdCDs produce combined photothermal and photodynamic effects. This not only results in tumor ablation but also induces immunogenic cell death (ICD), facilitating enhanced infiltration of CD8+ T cells in the tumor area. Importantly, the combination of aPD-L1 with photothermal and photodynamic therapies via aPD-L1@GdCDs significantly boosts CD8+ T cell infiltration, reduces tumor size, and improves anti-metastasis effects compared to either GdCDs-based phototherapy or aPD-L1 alone. In addition, the whole treatment process can be monitored by multi-modal fluorescence/photoacoustic/magnetic resonance imaging (FLI/PAI/MRI). Our study highlights a promising nanoplatform for cancer diagnosis and therapy, as well as paves the way to promote the efficacy of ICB therapy through mild photothermal- and photodynamic-triggered immunotherapy.

Impact of residual antibiotics on microbial decomposition of livestock manures in Eutric Regosol: Implications for sustainable nutrient recycling and soil carbon sequestration.

The land application of livestock manure has been widely acknowledged as a beneficial approach for nutrient recycling and environmental protection. However, the impact of residual antibiotics, a common contaminant of manure, on the degradation of organic compounds and nutrient release in Eutric Regosol is not well understood. Here, we studied, how oxytetracycline (OTC) and ciprofloxacin (CIP) affect the decomposition, microbial community structure, extracellular enzyme activities and nutrient release from cattle and pig manure using litterbag incubation experiments. Results showed that OTC and CIP greatly inhibited livestock manure decomposition, causing a decreased rate of carbon (28%-87%), nitrogen (15%-44%) and phosphorus (26%-43%) release. The relative abundance of gram-negative (G-) bacteria was reduced by 4.0%-13% while fungi increased by 7.0%-71% during a 28-day incubation period. Co-occurrence network analysis showed that antibiotic exposure disrupted microbial interactions, particularly among G- bacteria, G+ bacteria, and actinomycetes. These changes in microbial community structure and function resulted in decreased activity of urease, ß-1,4-N-acetyl-glucosaminidase, alkaline protease, chitinase, and catalase, causing reduced decomposition and nutrient release in cattle and pig manures. These findings advance our understanding of decomposition and nutrient recycling from manure-contaminated antibiotics, which will help facilitate sustainable agricultural production and soil carbon sequestration.

Insights into the Differences in Polysaccharide and Alkaloid Biosynthesis in the Medicinal Orchids Dendrobium nobile and D. officinale.

Both Dendrobium nobile and D. officinale are widely used medicinal plants in China and their major medicinal components are alkaloids and polysaccharides, respectively. It is still unclear why these two closely related orchids synthesize and accumulate different chemical components. Here, we investigated the molecular mechanisms underlying polysaccharide and alkaloid biosynthesis in D. nobile and D. officinale through transcriptome and metabolomic analysis at different growth stages. A total of 1267 metabolites were identified in the juvenile and mature stages of the two species. D. nobile accumulated a large number of alkaloids, benzenoids/phenylpropanoids, flavonoids, and terpenoids during the transition from juvenile to mature plants. In contrast, D. officinale accumulated a small number of those metabolites and an absence of flavonoids. The correlation analysis of polysaccharide contents with the differentially expressed genes suggested that the differential expression of GH1, GH3, and GH9 might be related to the difference in polysaccharide contents between the two Dendrobium species. Meanwhile, the difference in the biosynthesis of dendrobine, the main component of alkaloids in D. nobile, was involved in the differential expression of HMGCR, DXR, DXS, ISPH and eight CYP450s. These findings provided new insights into understanding the biosynthetic mechanisms of the main medicinal components in Dendrobium species.

ß-synuclein regulates the phase transitions and amyloid conversion of α-synuclein.

Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. ß-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that ß-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated ß-synuclein mutations lose these capacities. Exogenous ß-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated ß-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/ß-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and ß-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Microglial CR3 promotes neuron ferroptosis via NOX2-mediated iron deposition in rotenone-induced experimental models of Parkinson's disease.

The activation of complement receptor 3 (CR3) in microglia contributes to neurodegeneration in neurological disorders, including Parkinson's disease (PD). However, it remains unclear for mechanistic knowledge on how CR3 mediates neuronal damage. In this study, the expression of CR3 and its ligands iC3b and ICAM-1 was found to be up-regulated in the midbrain of rotenone PD mice, which was associated with elevation of iron content and disruption of balance of iron metabolism proteins. Interestingly, genetic deletion of CR3 blunted iron accumulation and recovered the expression of iron metabolism markers in response to rotenone. Furthermore, reduced lipid peroxidation, ferroptosis of dopaminergic neurons and neuroinflammation were detected in rotenone-lesioned CR3-/- mice compared with WT mice. The regulatory effect of CR3 on ferroptotic death of dopaminergic neurons was also mirrored in vitro. Mechanistic study revealed that iron accumulation in neuron but not the physiological contact between microglia and neurons was essential for microglial CR3-regulated neuronal ferroptosis. In a cell-culture system, microglial CR3 silence significantly dampened iron deposition in neuron in response to rotenone, which was accompanied by mitigated lipid peroxidation and neurodegeneration. Furthermore, ROS released from activated microglia via NOX2 was identified to couple microglial CR3-mediated iron accumulation and subsequent neuronal ferroptosis. Finally, supplementation with exogenous iron was found to recover the sensitivity of CR3-/- mice to rotenone-induced neuronal ferroptosis. Altogether, our findings suggested that microglial CR3 regulates neuron ferroptosis through NOX2 -mediated iron accumulation in experimental Parkinsonism, providing novel points of the immunopathogenesis of neurological disorders.

Apocarotenoids from the fresh roots of Rehmannia glutinosa and their anti-pulmonary fibrosis activity.

Six undescribed compounds (1-6) and twenty-three known analogues (7-29) were isolated from the fresh roots of Rehmannia glutinosa. The structures of the compounds (1-29) were established through the application of spectroscopic analysis. Compounds 3, 4, 6, 8, 13, 18, 21, 22, 25, and 28 exhibited excellent anti-pulmonary fibrosis activity. The potential mechanistic pathway of 3 was also investigated, whose results indicate that compound 3 ameliorate TGF-ß1 induced BEAS-2B cell injury via PI3K/AKT/NF-κB signaling pathway.

[Mechanism of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata herbal pair in promoting hepatocellular regeneration in chronic acute liver failure based on HGF/PI3K/Akt signaling axis].

Based on the hepatocyte growth factor(HGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling axis, this study investigated the therapeutic effect of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata(PRR-ALRP) her-bal pair on acute-on-chronic liver failure(ACLF) rats and its impact on hepatocellular regeneration. The rat model of ACLF was constructed by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of lipopolysaccharides(LPS)+D-galactosamine(D-GalN). The rats were divided into normal control(NC) group, model(vehicle) group, PRR-ALRP(5.85 g·kg~(-1)) group, and hepatocyte growth factor granules(HGFG, 4.05 g·kg~(-1)) group. Hematoxylin-eosin(HE) staining was used to observe pathological changes in rat liver tissues. Serum alanine aminotransferase(ALT), aspartate transaminase(AST), and total bilirubin(TBIL) were detected using an automatic biochemical analyzer. The levels of interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) inflammatory factors were detected by ELISA. Immunofluorescence staining was used to detect the positive expression of proliferating cell nuclear antigen(PCNA), antigen identified by monoclonal antibody(Ki67), and cell cycle protein B1(CyclinB1). Real-time fluorescence-based quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of HGF, growth factor receptor-bound protein 1(Gab1), PI3K, Akt, phosphorylated PI3K(p-PI3K), and phosphorylated Akt(p-Akt). The results showed that compared with the vehicle group, the PRR-ALRP group had reduced liver tissue pathological scores, improved liver function, and reduced inflammatory response, with enhanced PCNA, Ki67, and CyclinB1 fluorescence expression. Furthermore, compared with the model group, the PRR-ALRP group showed upregulated expression of HGF and Gab1 proteins, as well as activation of PI3K and Akt phosphorylation. These findings suggest that PRR-ALRP herbal pair exerts anti-liver failure effects by alleviating hepatocyte inflammatory damage and promoting hepatocellular regeneration, and its specific regulatory mechanism may be related to the activation of the HGF/PI3K/Akt signaling pathway.

[Influence of Tis108 on GA content and expression of key enzyme GeCYP714A1 involved in GA deactivation of Gastrodia elata].

To investigate the influence of the strigolactone inhibitor Tis108 on the growth of Gastrodia elata, this study treated G. elata tuber with Tis108 solution of 10 µmol·L~(-1) and measured the content of endogenous hormone gibberellin(GA) in the tuber. By using reverse transcription-polymerase chain reaction(RT-PCR) technology, the key enzyme GeCYP714A1 gene involved in GA deactivation was cloned. Bioinformatics analysis on the GeCYP714A1 gene was carried out by using ExPASy, SWISS-MODEL, MEGA, etc., and its expression levels in different parts of G. elata were determined. The results showed that after Tis108 treatment, GA content in G. elata tuber was significantly increased, and the transcription level of the GeCYP714A1 gene was significantly decreased. The full length of the coding region of the GeCYP714A1 gene is 1 173 bp, encoding 390 amino acids. The protein has a molecular weight of 44.85 kDa, a theoretical isoelectric point of 9.83, an instability index of 49.20, an aliphatic index of 89.03, and a grand average of hydropathicity of-0.235, classifying it as an unstable, basic, hydrophilic protein, and the GeCYP714A1 protein was localized in the mitochondria, lacking a signal peptide and a transmembrane structure. Phylogenetic tree analysis revealed that GeCYP714A1 was most closely related to the DcCYP714C2(PKU78454.1) protein from Dendrobium candidum, with a sequence identity of 67.25%. The qRT-PCR analysis of the expression patterns of the GeCYP714A1 gene indicated that GeCYP714A1 had the highest transcription level in G. elata tuber, followed by stem and inflorescence. The study represented that Tis108 inhibited the transcription level of GeCYP714A1 involved in GA deactivation in G. elata tuber, thereby increasing the accumulation of GA and affecting the growth of G. elata tuber. These results provided a basis for further studies of strigolactone regulation of GA signal and tuber development in G. elata.

[Acupuncture artery technique at Zusanli (ST 36) for Wagner grade 0 diabetic foot].

OBJECTIVE: To observe the clinical efficacy of acupuncture artery technique at Zusanli (ST 36) for Wagner grade 0 diabetic foot. METHODS: Sixty patients with Wagner grade 0 diabetic foot were randomly divided into an observation group and a control group, with 30 patients in each group. Both groups selected bilateral Zusanli (ST 36). In the control group, the needle was inserted about 10 mm under ultrasound guidance to avoid blood vessels in the Zusanli (ST 36) area, with needle retention for 5 min without manipulation. In the observation group, the needle was inserted about 25 mm under ultrasound guidance to the anterior tibial artery branch below Zusanli (ST 36), followed by lifting and thrusting manipulation for 5 min before withdrawing the needle. Both groups were treated twice a week for 4 weeks. The traditional Chinese Medicine (TCM) syndrome scores were observed; infrared thermography was used to measure the temperature difference between the left and right sides in four areas, i.e. the medial malleolus, lateral malleolus, and upper and lower parts of the sole of the foots; Doppler ultrasound was used to measure the logarithm of the peak systolic velocity (ln PS) and the logarithm of the time average maximum velocity (ln TAMAX) of the anterior tibial artery below the right Zusanli (ST 36); the ankle-brachial index (ABI) was measured using Doppler blood flow detector and blood pressure monitor before treatment, after the first treatment, and at the end of treatment. Clinical efficacy was compared between the two groups. RESULTS: Compared before treatment, the TCM syndrome scores in both groups were reduced after the first treatment and at the end of treatment (P<0.01, P<0.05), and the scores in the observation group were lower than those in the control group (P<0.01). In the observation group, compared before treatment, the maximum, minimum, and average temperature differences between the left and right sides of the upper and lower parts of the sole of the foots, medial malleolus, and lateral malleolus were reduced after the first treatment and at the end of treatment (P<0.05, P<0.01). After the first treatment, the maximum temperature difference between the left and right sides of the upper part of the sole of the foots and the medial malleolus in the observation group was lower than that in the control group (P<0.05). At the end of treatment, except for the average temperature difference of the medial malleolus, the maximum, minimum, and average temperature differences between the left and right sides of the upper and lower parts of the sole of the foots, medial malleolus, and lateral malleolus in the observation group were lower than those in the control group (P<0.01, P<0.05). After the first treatment and at the end of treatment, the ln PS, ln TAMAX, and ABI of the anterior tibial artery below the right Zusanli (ST 36) in the observation group were higher than those before treatment (P<0.01) and higher than those in the control group (P<0.01). The total effective rate in the observation group was 96.7% (29/30), higher than 3.3% (1/30) in the control group (P<0.05). CONCLUSION: Acupuncture artery technique at Zusanli (ST 36) could effectively improve the clinical symptoms of patients with Wagner grade 0 diabetic foot, increase blood flow velocity in the lower limb vessels, and reduce the temperature difference between the left and right lower limbs.

Comparing effects of high starch diet or high lipid diet supplemented with different levels of zinc on intestinal barrier and microbe community in largemouth bass Micropterus salmoides.

Zinc is essential for normal growth and reproduction in all animals and plays a crucial role in many biological processes. The present study aimed to compare the intervention effects of zinc on intestinal health in a high lipid diet or high starch diet. Seven iso-nitrogenous (∼520 g kg-1) diets were formulated containing a positive control diet (115 g kg-1 lipid + 115 g kg-1 starch + 20 mg kg-1 Zn), three high starch diets (HS, 166 g kg-1 starch) and three high lipid diets (HL, 182 g kg-1 lipid), with 0 (HS-LZn, HL-LZn), 20 (HS-MZn, HL-MZn) and 150 (HS-HZn, HL-HZn) mg kg-1 Zn being supplemented. High starch diet and high lipid diet promoted feed efficiency, as evidenced by the lower feed conversion ratio. Three-way factorial ANOVA analysis showed high starch diet (166 g kg-1) significantly decreased final body weight and weight gain compared to the normal starch level (115 g kg-1). Diamine oxidase in serum significantly increased in diets HS-LZn and HL-LZn. In addition, distal intestinal mucosal fold damage and inflammatory infiltration were observed in the HS-LZn, HS-HZn, HL-LZn and HL-HZn groups. Fish fed HL diets (HL-LZn, HL-MZn, HL-HZn) showed lower expressions of claudin 5 and claudin 34, and higher IgD and IgM. Diets HL-LZn and HL-MZn significantly up-regulated C4 and C7. Proinflammatory cytokines including il8, il1ß and tnfα significantly up-regulated in diet HL-LZn, even higher than the HS-LZn. Intestinal microbial composition indicated the abundance of Cetobacterium in HL-LZn was significantly higher than the control and HL-MZn diets. Similarly, LEfSe showed that Cetobacterium (P = 0.039) significantly enriched in the HL-LZn group. This study clarified high energy diet induced intestinal damage, which can be alleviated by zinc.

Pegaharolines A - I, structurally novel indole alkaloids with anti-HSV-2 virus activities from Peganum harmala L. seeds.

Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A - I (1-9), and 11 known ones (10-20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5-6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1-6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC50 = 0.90 ± 0.10 µM) was much better than that of the positive control (acyclovir, IC50 = 1.12 ± 0.15 µM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products.

[Pharmacoeconomic evaluation of Shaoma Zhijing Granules in treatment of tic disorders in children].

This study conducted a pharmacoeconomic evaluation of Shaoma Zhijing Granules in the treatment of tic disorder(TD) in children. Firstly, from the perspective of the healthcare system, cost-effectiveness analysis was used to evaluate the economic efficiency of Shaoma Zhijing Granules compared with Changma Xifeng Tablets and Jiuwei Xifeng Granules in the treatment of TD in children. Then, through network Meta-analysis, the overall effectiveness of different regimens was calculated, combined with the total cost of the regimens, to calculate the incremental cost-effectiveness ratio(ICER). Finally, sensitivity analysis was performed to verify the stability of the study results and the credibility of the conclusions. This study included 17 articles, including 9 articles on Chinese patent medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 4 on Changma Xifeng Tablets), for the treatment of TD in children, and 8 articles on Chinese patent medicines combined with conventional western medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 3 on Changma Xifeng Tablets). In the Chinese patent medicine group, the total cost of Shaoma Zhijing Granules for treating TD was CNY 4 410.00, with clinical total effective rate of 77.53%; the total cost of Jiuwei Xifeng Granules for treating TD was CNY 5 192.70, with clinical total effective rate of 82.13%. The ICER of Jiuwei Xifeng Granules vs Shaoma Zhijing Granules was 169.95, higher than the willingness-to-pay(WTP, cost of increasing efficiency by 1% is CNY 85.70). Therefore, Jiuwei Xifeng Granules did not have a cost-effectiveness advantage over Shaoma Zhijing Granules. The total cost of Changma Xifeng Tablets for treating TD was CNY 1 282.50, with clinical total effective rate of 80.60%. The total cost of Changma Xifeng Tablets was lower and clinical total effective rate was higher than that of Shaoma Zhijing Granules. Overall, Shaoma Zhijing Granules did not have a cost-effectiveness advantage. In the Chinese patent medicine combined with conventional western medicine group, the total cost of Shaoma Zhijing Granules for treating TD + conventional western medicines was CNY 6 768.52/6 778.48, with clinical total effective rate of 96.18%. The total cost of Jiuwei Xifeng Granules + conventional western medicines for treating TD was CNY 6 522.56, with clinical total effective rate of 88.30%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Jiuwei Xifeng Granules + conventional western medicines was 31.20, lower than WTP. Therefore, Shaoma Zhijing Granules + conventional western medicines had a cost-effectiveness advantage over Jiuwei Xifeng Granules + conventional western medicines. The total cost of Changma Xifeng Tablets + conventional western medicines for treating TD was CNY 1 706.12, with clinical total effective rate of 95.39%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Changma Xifeng Tablets + conventional western medicines was 6 334.06, higher than WTP. Therefore, although Shaoma Zhijing Granules + conventional western medicines had higher clinical total effective rate compared with Changma Xifeng Tablets + conventional western medicines, it did not have a cost-effectiveness advantage. Overall, for different medication regimens(Chinese patent medicines monotherapy or in combination with conventional western medicines), Shaoma Zhijing Granules and Jiuwei Xifeng Granules both had a cost-effectiveness advantage, but compared with Changma Xifeng Tablets, neither had a cost-effectiveness advantage. For Chinese patent medicines in combination with conventional western medicines, clinical total effective rate of Shaoma Zhijing Granules in combination with conventional western medicines for the treatment of TD in children was the highest.

Immune, Oxidative, and Morphological Changes in the Livers of Tibetan Sheep after Feeding Resveratrol and ß-Hydroxy-ß-methyl Butyric Acid: A Transcriptome-Metabolome Integrative Analysis.

This study investigated the effects of dietary resveratrol (RES) and ß-Hydroxy-ß-methyl butyric acid (HMB) on immune, oxidative, and morphological changes in the livers of Tibetan sheep using transcriptomics and metabolomics. One hundred and twenty male Tibetan lambs of a similar initial weight (15.5 ± 0.14 kg) were randomly divided into four groups with thirty lambs per treatment: (1) H group (basal diet without RES or HMB); (2) H-RES group (1.5 g/day of RES); (3) H-HMB group (1250 mg/day of HMB); (4) H-RES-HMB group (1.5 g/day of RES and 1250 mg/day of HMB). The experiment was conducted for 100 days, including a pre-test period of 10 days and a formal period of 90 days. The results showed significantly increased concentrations of glutathione peroxidase, superoxide dismutase, and IgM in the H-RES-HMB group (p < 0.05), while the malondialdehyde levels were significantly decreased (p < 0.05). The glycolytic indices including creatinine kinase (CK), malate dehydrogenase (MDH), and succinate dehydrogenase (SDH) were significantly increased in the H-RES-HMB group compared with the others (p < 0.05). A histological analysis showed that the hepatic plate tissue in the H-RES-HMB group appeared normal with multiple cells. The transcriptomic analysis showed that the expression of genes associated with the calcium signaling pathway (MYLK2, CYSLTR2, ADCY1, HRH1, ATP2B2, NOS2, HRC, ITPR1, and CAMK2B) and the NF-κB signaling pathway (BCL2 and CARD14) in the H-RES-HMB group were upregulated. The key differential metabolites (d-pyroglutamic acid, DL-serine, DL-threonine, fumarate, and glyceric acid) were enriched in the pathways associated with D-amino acid metabolism, the citrate cycle (TCA cycle), and carbon metabolism. The combined transcriptomic and non-targeted metabolomic analyses showed the co-enrichment of differential genes (NOS2 and GLUD1) and metabolites (fumarate) in arginine biosynthesis-regulated glycolytic activity, whereas the differential genes (ME1, SCD5, FABP2, RXRG, and CPT1B) and metabolites (Leukotriene b4) co-enriched in the PPAR signaling pathway affected the immune response by regulating the PI3K/AKT and cGMP/PKG signaling. In conclusion, the dietary RES and HMB affected the hepatic antioxidant capacity, immune response, and glycolytic activity through modulating the transcriptome (BCL2, CAMK2B, ITPR1, and IL1R1) and metabolome (DL-serine, DL-threonine, fumaric acid, and glycolic acid).

[Advances in in vitro assessment models and screening methods for blood glucose-lowering medications].

Diabetes, a common metabolic condition, is recognized by the worldwide public health community as a serious chronic illness. International new drug discovery has long been dominated by the study and creation of blood glucose-lowering medications. Important phases in the development process of these medications include the in vitro assessment model and screening methods, which can dramatically lower the costs and risks of subsequent clinical trials and increase the effectiveness and efficiency of drug development. This article reviews the classic and latest cutting-edge in vitro assessment models, principles, methods, and key technologies for blood glucose-lowering medications both domestically and internationally. By objectively evaluating their advantages, disadvantages, characteristics, applicability, experimental design, and data analysis, this article aims to improve the standardization and consensus of in vitro assessment models and screening methods and serve the research and development of blood glucose-lowering medications.

High-frequency magnetic paired associated stimulation promotes motor function recovery in ischemic stroke patients: a study protocol for single-center, sham stimulation randomized controlled trials (H2MPAS).

BACKGROUND: Numerous studies have validated the clinical effectiveness of electromagnetic pairing-associated stimulation. Building upon this foundation, we have developed a novel approach involving high-frequency magnetic paired-associated stimulation, aiming to enhance clinical applicability and potentially improve efficacy. However, the clinical effectiveness of this approach remains unclear. Our objective is to demonstrate the therapeutic efficacy of this novel approach by employing high-frequency pairing to intervene in patients experiencing motor dysfunction following a stroke. METHODS: This is a single-center, single-blind, sham stimulation controlled clinical trial involving patients with upper limb motor dysfunction post-stroke. The intervention utilizes paired magnetic stimulation, combining peripheral and central magnetic stimulation, in patients with Brunnstrom stage III-V stroke lasting from 3 months to 1 year. Evaluation of patients' upper limb motor function occurred before the intervention and after 3 weeks of intervention. Follow-up visits will be conducted after 5 weeks and 3 months of intervention. The primary outcome measure is the Action Research Arm Test, with secondary measures including the Fugl-Meyer Assessment-upper, Modified Barthel Index, modified Tardieu scale, functional near-infrared spectroscopy, and neuroelectrophysiology. DISCUSSION: The high-frequency magnetic paired associative stimulation used in this study combined high-frequency magnetic stimulation with paired stimulation, potentially facilitating both cortical excitation through high-frequency stimulation and specific circuit enhancement through paired stimulation. As dual-coil magnetic stimulation equipment becomes increasingly popular, magnetic-magnetic paired associated stimulation may offer patients improved clinical outcomes at reduced costs. TRIAL REGISTRATION: Chinese Clinical Trial Registry,ChiCTR2400083363. Registered on 23 April 2024.

[Constructing an indexing template for ancient acupuncture medical cases based on knowledge element theory].

Ancient acupuncture medical cases not only possess historical literary value but also hold significant clinical importance. To enhance the utilization of ancient acupuncture medical cases and to guide the excavation of acupuncture theory and its clinical application, this study constructs an indexing template for "Ancient Acupuncture Medical Cases" based on the knowledge element theory and the fine-grained indexing requirements of ancient acupuncture texts. This template includes two levels, 7 categories, 28 knowledge element data, 31 semantic types, and 15 semantic relationships. These element data construct the interconnections of knowledge in ancient acupuncture medical cases, serving as a basis for fine-grained indexing of acupuncture medical case literature.

Geniposide attenuates influenza virus-induced pneumonia by regulating inflammatory cytokines production. Evidences to elucidate the followed pathway.

BACKGROUND: Influenza virus-induced pneumonia (IVP) is an infectious pulmonary disease characterized by exacerbated pulmonary inflammation caused by invasion of the influenza virus. IVP continues to threaten public health due to its high morbidity and mortality rates. Geniposide is one of the major bioactive constituents of G. jasminoides, which exerts antiviral and anti-inflammatory effects on influenza A virus (IAV) infection. PURPOSE: To investigate therapeutic effects and comprehensive mechanisms of geniposide on IAV infection and subsequent pneumonia. METHODS: ICR mice were infected intranasally with H1N1 (A/FM/1/47) to detect the anti-IAV activity of geniposide. Proteomics combined with function-integrated analysis were conducted to gain insight into the comprehensive mechanisms of geniposide. Subsequently, western blot was used to detect the phosphorylation of signal transducer and activator of transcription 1 (STAT1), signal transducer and activator of transcription 2 (STAT2), Interferon regulatory factor 9 (IRF9) and Janus kinase 1 (JAK1) in Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in lung tissue. Finally, RT-qPCR was used to detect the levels of interleukin 6 (IL-6), interleukin 17 (IL-17), interferon-γ (IFN-γ) and the STAT1 inhibitor (fludarabine) was used to verify the targeting between STAT1 and geniposide in RAW cells. RESULTS: Geniposide could significantly reduce the lung index, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by IAV infection. A total of 411 differentially expressed proteins were identified among control, model, and geniposide-treated group in proteomic analysis. According to function-integrated analysis, 15 KEGG pathways were enriched and divided into 9 groups (modules), including influenza A, NOD-like receptor signaling, RIG-I-like receptor signaling, and so on. Among these modules, the most intensely interacting module pair was the NOD-like receptor signaling and influenza A, in which STAT1 and STAT2 acted as hubs with critical bridgeness role in the target network of geniposide. This indicated that geniposide may mitigate inflammation and alleviate IVP by JAK/STAT signaling pathways. Moreover, validation experiments confirmed that geniposide can significantly inhibit STAT1 and STAT2 phosphorylation as well as down-regulated expression of IL-6, IFN-γ and IL-17 in lung. Furthermore, when RAW cells were treated with the STAT1 inhibitor (fludarabine), the inhibitory effect of geniposide on IFN-γ and IL-6 was attenuated significantly. CONCLUSIONS: Geniposide can attenuate IAV-induced pneumonia by regulating inflammatory cytokines production through the JAK/STAT pathway.

Association of variant vitamin statuses and tuberculosis development: a systematic review and meta-analysis.

BACKGROUND: Several studies have suggested an association between vitamin deficiency and the development of tuberculosis; however, the precise impact remains unclear. This study aimed to elucidate the relationship between distinct vitamin statuses and the occurrence of tuberculosis. MATERIALS AND METHODS: Retrieval was conducted using several databases without language restrictions to capture the eligible studies on tuberculosis and vitamin status. Pooled odds ratios (ORs), relative risks (RRs), and hazard ratios (HRs) were used with 95% confidence intervals (CIs) to clarify the relationship between the different vitamin statuses (A, B, D, and E) and the occurrence of tuberculosis. Subgroup analysis, sensitivity analysis, meta-regression analysis, and Galbraith plot were performed to determine sources of heterogeneity. Potential publication biases were detected using Begg's test, Egger's test, and the trim-and-fill test. RESULTS: We identified 10,266 original records from our database searches, and 69 eligible studies were considered in this study. The random-effect model showed that people with tuberculosis may exhibit vitamin A deficiency (OR = 10.66, 95%CI: 2.61-43.63, p = .001), while limited cohort studies showed that vitamin A supplementation may reduce tuberculosis occurrence. Additionally, vitamin D deficiency was identified as a risk factor for tuberculosis development (RR = 1.69, 95%CI: 1.06-2.67, p = .026), and people with tuberculosis generally had lower vitamin D levels (OR = 2.19, 95%CI: 1.76-2.73, p < .001) compared to other groups. No publication bias was detected. CONCLUSIONS: This meta-analysis indicated that people with tuberculosis exhibited low levels of vitamins A and D, while vitamin D deficiency was identified as a risk factor for tuberculosis. More randomized controlled interventions at the community levels should be recommended to determine the association between specific vitamin supplementation and tuberculosis onset.