Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry* ; Greenhouse Gases/metabolism* ; Carbon/analysis* ; Ecosystem ; Carbon Dioxide/metabolism* ; China ; Global Warming

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections

This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.
Semen Analysis/standards* ; Humans ; China ; Male ; Quality Control ; Sperm Motility ; Sperm Count/standards*

Objective:To investigate the correlation between lymphocyte-monocyte ratio (LMR) and long-term prognosis after distal cholangiocarcinoma.Methods:A retrospective case-control study was conducted to analyze the clinical data of 186 patients with distal cholangiocarcinoma who underwent radical pancreaticoduodenectomy at Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2013 to December 2023. Among them, there were 109 males and 77 females, with an age of (65.4±9.4) years, ranging from 29 to 85 years. The data of preoperative peripheral blood routine examination of the patients were collected, and the patients were divided into a high LMR group(LMR>2.98, n=100) and a low LMR group(LMR≤2.98, n=86). The preoperative, intraoperative and postoperative clinical characteristics of the two groups were compared. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. Measurement data with non-normal distribution were expressed as M( Q1, Q3), and Mann-Whitney U test was used for inter-group comparison. Chi-square test was used for inter-group comparison of count data. The Cox proportional hazards regression model was used for univariate and multivariate prognostic analysis, and the Kaplan-Meier estimation method was used to create survival curves to analyze and evaluate the influencing factors of long-term prognosis after distal cholangiocarcinoma surgery. Results:Univariate analysis results showed that gender, age, BMI, history of diabetes, carcinoembryonic antigen; operation duration, intraoperative blood loss; resection margin status, degree of tumor cell differentiation, and presence of postoperative complications had no statistically significant differences in their impact on the prognosis of patients after distal cholangiocarcinoma surgery( P>0.05). In contrast, LMR, neutrophilto-lymphocyte ratio, platelet-lymphocyte ratio, albumin, total bilirubin, carbohydrate antigen 199, intraoperative blood transfusion, tumor diameter, and lymph node metastasis showed statistically significant differences in their influence on the postoperative prognosis of distal cholangiocarcinoma patients( P<0.05). Multivariate analysis results indicated that LMR≤2.98( HR=1.776, 95% CI: 1.153-2.736), CA19-9>37 U/mL( HR=1.521, 95% CI: 1.025-2.259), and lymph node metastasis( HR=1.601, 95% CI: 1.106-2.318) were independent risk factors affecting patient prognosis( P<0.05). The 1-, 3-, and 5-year cumulative survival rates in the high LMR group were 91%, 40%, and 20% respectively, while those in the low LMR group were 58.1%, 15.1%, and 8.1% respectively, with a statistically significant difference( P<0.05). Conclusion:Preoperative LMR for distal cholangiocarcinoma can suggest a long-term prognosis, and a low LMR value suggests a poor prognosis.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective:To investigate the impact of Tumor-Infiltrating Lymphocytes (TILs) density in the tumor stroma on the long-term prognosis of hepatocellular carcinoma (HCC) liver transplant patients meeting the Hangzhou criteria.Methods:This study is a retrospective cohort study. The clinical data of 83 patients with hepatocellular carcinoma who met the Hangzhou criteria and underwent allogeneic liver transplantation from January 2018 to December 2023 in the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University were collected and analyzed. Hematoxylin and Eosin (HE) staining was used to study the density of TILs in the resected liver grafts. Patients were divided into TILs-negative group (TILs<10%, n=31) and TILs-positive group (TILs≥10%, n=52) based on whether the TILs density exceeded 10%. Clinical and pathological characteristics were analyzed, and the significance of alpha-fetoprotein (AFP), TILs density, and microvascular invasion on the prognosis of HCC patients who met the Hangzhou criteria was studied. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared between groups using t-test. Measurement data with skewed distribution were expressed as M ( Q1, Q3) and compared using rank-sum tests. Categorical data were compared using chi-square test. Kaplan-Meier method was used to study the relationship between various observation indicators and overall survival, and survival curves were plotted. Log-rank test was used to compare the survival rates between groups, and multivariate Cox regression model was used to adjust for the distribution of risk factors between groups. Results:The preoperative AFP level in the TILs-negative group was (15.69±1.21) U/mL, and in the TILs-positive group was (12.17±0.13) U/mL, with a statistically significant difference between the two groups ( P<0.05). In the TILs-negative group, 8 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 8, 23, and 0, respectively. In the TILs-positive group, 3 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 2, 31, and 19, respectively. The results indicated that patients in the TILs-negative group were more likely to have microvascular invasion and poorer tumor differentiation ( P<0.05). All patients were regularly followed up, and the 1-, 2-, and 3-year survival rates in the TILs-negative group and TILs-positive group were 84.0%, 77.6%, 69.8%, and 94.7%, 91.7%, 86.6%, respectively ( P<0.01). Cox proportional hazards model indicated that microvascular invasion ( RR=4.474, 95% CI: 1.172-17.072, P=0.028) and TILs-negative status ( RR=5.081, 95% CI: 1.420-18.184, P=0.012) were independent risk factors for the long-term prognosis of HCC patients who met the Hangzhou criteria. Conclusions:Among HCC patients meeting the Hangzhou criteria, the density of TILs in the tumor stroma is related to AFP levels, tumor differentiation, and the presence of microvascular invasion. TILs-negative status indicates a poorer prognosis for these patients.

Objective:Osteosarcoma is the most common malignant bone tumor in children and adolescents,characterized by a high potential for proliferation and metastasis.Patients with osteosarcoma who have distant metastases generally have a poor prognosis.Challenges in treatment include incomplete resection of tumor and chemotherapy resistance,with no effective cure currently available.Recent studies suggest that β-1,4-N-acetyl-galactosaminyltransferase 1(B4GALNT1)plays a role in the progression of various malignant tumors.However,the function of B4GALNT1 in osteosarcoma cells has not been reported.This study aims to investigate the expression of B4GALNT1 in osteosarcoma tissues compared to normal tissues and to explore its effects on the proliferation,migration,and invasion of osteosarcoma cells,thereby providing new theoretical foundations and directions for the treatment of osteosarcoma patients. Methods:Tumor tissues and corresponding normal tissue samples were collected from 16 osteosarcoma patients who underwent tumor resection at the Second Xiangya Hospital of Central South University.The patients'ages ranged from 8 to 17 years(median age 12 years).The expression of B4GALNT1 mRNA in osteosarcoma tissues,corresponding normal tissues,3 osteosarcoma cell lines(MG63,Saos-2,and U2OS),and human fetal osteoblastic cells(hFOB)was detected using real-time reverse transcription PCR(real-time RT-PCR).The effects of B4GALNT1 knockdown on the proliferation of osteosarcoma cells Saos-2 and U2OS were analyzed using cell counting kit-8(CCK-8)assays and colony formation assays.The effects of B4GALNT1 knockdown on the migration and invasion abilities of Saos-2 and U2OS cells were evaluated using Transwell migration and invasion assays.Western blotting analysis was performed to assess the impact of B4GALNT1 knockdown on the expression of epithelial-mesenchymal transition(EMT)and invasion-related proteins in Saos-2 and U2OS cells. Results:Real-time RT-PCR results showed that B4GALNT1 mRNA expression levels were significantly higher in osteosarcoma tissues and the 3 osteosarcoma cell lines compared to normal tissues and hFOB cells(all P＜0.0 1).CCK-8 and colony formation assays indicated that B4GALNT1 knockdown significantly reduced the proliferation rate of osteosarcoma cells compared to the control group(all P＜0.05).Transwell migration and invasion assays demonstrated that B4GALNT1 knockdown significantly decreased the number of migrating and invading osteosarcoma cells(all P＜0.01).Western blotting analysis revealed that B4GALNT1 knockdown inhibited the expression of N-cadherin,Snail,Vimentin,and matrix metalloproteinase 9(MMP9)compared to the control group(all P＜0.01). Conclusion:B4GALNT1 is upregulated in osteosarcoma tissues and cell lines,and its knockdown suppresses the malignant phenotype of osteosarcoma cells.B4GALNT1 may function as an oncogene in the proliferation and metastasis of osteosarcoma cells.

Objective To investigate the impact of matrine(Mat)on renal injury in rats with chronic glomerulonephritis by regulating the monocyte chemotactic protein-1(MCP-1)/chemokine C-C-motif receptor 2(CCR2)signaling pathway.Methods The rat model of chronic glomerulonephritis was established by subcutaneous injection of bovine serum albumin,the rats were randomly grouped into control group,model group,low and high dose matrine groups(Mat-L group,Mat-H group),and matrine+CCR2 group(Mat+CCR2 group),with 10 rats in each group.After continuous gavage for 4 weeks,24-hour urine protein excretion was measured;spleen and thymus were removed and organ index was calculated;The levels of blood urea nitrogen(BUN)and serum creatinine(Scr)in the serum of each group were detected,the pathological changes of renal tissue were observed by HE staining;the levels of tumor necrosis factor α(TNF-α)and interleukin(IL)-6 in renal tissue were detected by ELISA;Flow cytometry was applied to detect the proportion of T lymphocyte subsets in peripheral blood of rats in each group;Western blotting was applied to determine the expression of MCP-1 and CCR2 proteins.Results The spleen index and thymus index of rats in the model group rats were obviously reduced,and there were a large number of inflammatory cell infiltration in the renal tissue,the 24-hour urine protein,BUN,Scr,TNF-α,IL-6,and the expression of MCP-1 and CCR2 obviously increased,the peripheral blood T cell subpopulations CD3+,CD4+,and CD4+/CD8+ratio obviously reduced,the proportion of CD8+obviously increased(P＜0.05);The spleen index and thymus index of rats in the Mat-L and Mat-H groups of rats increased,and the phenomenon of renal tissue inflammation and infiltration improved,the 24-hour urine protein,BUN,Scr,TNF-α,IL-6,and the expression of MCP-1 and CCR2 obviously decreased,the peripheral blood T cell subpopulations CD3+,CD4+,and CD4+/CD8+ratio obviously increased,the proportion of CD8+obviously decreased(P＜0.05);CCR2 attenuated the effect of Mat-H on immune function in rats with chronic glomerulonephritis.Conclusion Matrine can alleviate the inflammatory damage and improve the peripheral immune function of rats with chronic glomerulonephritis,and its mechanism may be related to the inhibition of MCP-1/CCR2 signaling pathway.

Objective:To explore the causal relationship between human inhalation injury and circulating inflammatory proteins.Methods:This research was based on two-sample Mendelian randomization (MR) analysis. With inhalation injury as the exposure factor and circulating inflammatory proteins as the result, data on inhalation injury (216 993 samples) and 91 circulating inflammatory proteins (14 824 samples) were obtained from the genome-wide association study database, and analysis was conducted by two-sample MR analysis methods. Based on linkage disequilibrium analysis, independent site single nucleotide polymorphisms (SNPs) that were significantly associated with inhalation injury were identified as the instrumental variables. The inverse variance weighted (IVW) method was mainly used to analyze the causal relationship between inhalation injury and 91 circulating inflammatory proteins, which were further verified using the weighted median method, weighted pattern method, MR-Egger method, and simple pattern method. Based on the aforementioned IVW method analysis results, SNPs of inhalation injury conformed to the hypothesis were subjected to Cochran's Q test for heterogeneity assessment, the MR-Egger regression test and MR-PRESSO outlier test for assessment of horizontal pleiotropy, and the leave-one-out method analysis for reliability assessment.Results:Six SNPs with a significant threshold ( P<5×10 -5) were identified as representative instrumental variables of inhalation injury, with F values greater than 10, indicating strong correlated instrumental variables. Based on the 6 inhalation injury SNPs, the IVW method analysis revealed a significant causal relationship between inhalation injury and interleukin-20 (IL-20), IL-20 receptor subunit alpha (IL-20RA), IL-5, and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), with odds ratios of 1.01, 1.01, 1.02, and 1.01, respectively, and 95% confidence intervals of 1.00-1.02, 1.00-1.03, 1.01-1.03, and 1.00-1.03, respectively, P<0.05. Verification through the weighted median method and MR-Egger method confirmed that the causal relationships between inhalation injury and IL-5 (with odds ratios of 1.02 and 1.03, respectively, confidence intervals of 1.00-1.04 and 1.01-1.04, respectively, P<0.05) as well as TNFRSF9 (with odds ratios of 1.02 and 1.03, respectively, confidence intervals of 1.00-1.04 and 1.01-1.04, respectively, P<0.05) were statistically significant. Conversely, verification through the weighted pattern method and simple pattern method indicated that the causal relationships between inhalation injury and IL-20, IL-20RA, IL-5, and TNFRSF9 were not statistically significant (with all P values >0.05), thus still needing IVW method results as standards. Based on the aforementioned IVW method analysis results, the Cochran's Q test demonstrated there was no significant heterogeneity in the 6 inhalation injury SNPs that had significant causal relationships with IL-20, IL-20RA, IL-5, and TNFRSF9 (with Q values of 2.67, 5.00, 5.17, and 5.29, respectively, P>0.05); assessments using the MR-Egger regression test along with MR-PRESSO outlier test showed that none of the 6 inhalation injury SNPs that had significant causal relationships with IL-20, IL-20RA, IL-5, and TNFRSF9 had significant horizontal pleiotropy (with intercepts of 0.01, <0.01, -0.02, and -0.03, respectively, RSSobs values of 3.33, 9.00, 7.88, and 7.26, respectively, P>0.05); the leave-one-out method analysis showed that the significant causal relationship between inhalation injury and IL-20, IL-20RA, IL-5, and TNFRSF9 was stable and reliable after removing the 6 inhalation injury SNPs one by one. Conclusions:Through two-sample MR analysis, it is clear that there is a significant causal relationship between inhalation injury and four circulating inflammatory proteins, namely IL-20, IL-20RA, IL-5, and TNFRSF9, suggesting the production of the above four circulating inflammatory proteins is in an increasing trend following inhalation injury.