This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

Climate and land use changes may significantly impact the habitat distribution of Gastrodia elata, an endangered traditional medicinal plant. Accurately predicting its future potential suitable habitats is crucial for its conservation and sustainable development. This study integrates current distribution data of G. elata with 56 environmental variables and uses the MaxEnt model to predict changes in its suitable habitats under current climate conditions and four future climate scenarios(SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The results show that October precipitation and December minimum temperature are key environmental factors influencing its distribution. Under the current climate, optimal habitats for G. elata are concentrated in montane forest areas in Sichuan, Yunnan, Guizhou, and Hubei, which meet the species' requirements for understory growth. Across all future scenarios, the suitable habitat of G. elata consistently shows a stable northward shift, with a steady increase in suitable areas, extending to the middle and lower reaches of the Yangtze River and the Huang-Huai region, and even expanding into Liaoning, Jilin, and southern Heilongjiang. Land use analysis, taking into account the protection of arable land and the utilization of forest resources, indicates that by 2100, under future climate conditions, arable land in medium-to high-suitability areas is expected to increase by 30%-124%. While the conversion of non-suitable forest land into suitable habitats is projected to increase by 5%-52%, the growth of medium-to high-suitability areas within forests is relatively modest, ranging from 1% to 24%. These findings highlight the need to balance agricultural expansion with forest resource conservation to ensure the long-term sustainability of G. elata and provide scientific guidance for future suitable habitat management.
Ecosystem ; China ; Climate Change ; Gastrodia/growth & development* ; Conservation of Natural Resources ; Plants, Medicinal/growth & development*

OBJECTIVE: To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele（VC）with male infertility. METHODS: A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis. The patients were divided into the microscopic group (180 cases) and laparoscopic group (127 cases) according to the surgery method. The pre- and postoperative clinical data of these two groups were analyzed, including the degree of dilatation and reflux time of internal spermatic vein，hemodynamic parameters of testicular capsular artery，proportion of progressive motility spermatozoa (PR), concentration of spermatozoa, proportion of normal morphology sperm，the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively. RESULTS: All the surgeries for the 307 patients in this study were successful. There was no significant difference in operation time, hospitalization time and management expenses between the microscopic group and the laparoscopic group (P>0.05). Compared to the patients in laparoscopic group, the patients in the microscopic group received a better improvement in venous diameter, reflux time of spermatic veins and hemodynamic parameters of testicular capsular artery (P<0.05). Moreover, the semen analysis showed that the PR, spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group (P<0.05). During the 2-year follow-up period, the conception rate of spouses in the microscopic group was 67.2%, while only 47.2% in the laparoscopic group, in which the difference was statistically significant (P<0.05). Besides, the time-to-pregnancy ( TTP ) within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group（P<0.05). Meanwhile, the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group (P<0.05). It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group (P<0.05). Severe complication such as testicular atrophy, bleeding and infection did not appear in both of two groups. However, the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group (P<0.05). CONCLUSION Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility. But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters, semen quality, pregnancy outcome and postoperative complications, which is worthy of further clinical applications.
Humans ; Male ; Varicocele/complications* ; Laparoscopy ; Infertility, Male/etiology* ; Retrospective Studies ; Adult ; Microsurgery ; Treatment Outcome ; Pregnancy ; Female

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

AIM To investigate the clinical effects of Feining Paidu Decoction combined with conventional treatment on patients with Mycoplasma pneumoniae lobar pneumonia.METHODS Ninety patients were randomly assigned into control group(45 cases)for 2-week intervention of conventional treatment,and observation group(45 cases)for 2-week intervention of both Feining Paidu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,inflammatory indices(WBC,N,CRP,ESR,PCT),inflammatory cytokines(TNF-α,IL-6,IL-8),coagulation indices(PLT,TT,PT,APTT,Fib,D-D),pulmonary imaging intergal and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,inflammatory indices,inflammatory cytokines,PLT,pulmonary imaging intergal(P<0.05),especially for the observation group(P<0.05);the observation group exhibited prolonged TT,PT,APTT(P<0.05),and decreased Fib,D-D(P<0.05),which were more obvious than those in the control group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with Mycoplasma pneumoniae lobar pneumonia,Feining Paidu Decoction combined with conventional treatment can safely and effectively alleviate clinical symptoms,and improve inflammatory responses,coagulation functions.

Objective:To investigate the correlation between immune function and age-related pulmonary fibrosis, as well as the potential impact of bacterial lysates on this condition.Methods:Twenty-four healthy male C57BL/6 mice, aged 24, were randomly divided into three groups: a control group(Group N), a pulmonary fibrosis group(Group M), and a pulmonary fibrosis+ bacterial lysis product intervention group(Group P). Mice in Groups M and P were intratracheally injected with bleomycin(5 mg/kg)to induce a mouse pulmonary fibrosis model, while mice in Group N were injected with saline.After modeling, mice in Group P were orally administered 0.4 ml of a bacterial lysis product once a day.After 28 days, lung tissue and blood samples were collected for analysis.Pathological changes in lung tissue were assessed using hematoxylin and tosin staining(HE)and Masson staining and the Ashcroft score.The expression of CD4+ and CD8+ in lung tissue was evaluated using immunohistochemistry.The levels of serum interferon-γ(INF-γ), interleukin-3(IL-13), and immunoglobulin A(IgA)protein were measured using Enzyme-linked Immuno Sorbent Assay(ELISA). The levels of INF-γ and IL-13 mRNA in lung tissue were determined using Real-Time Quantitative Transcription PCR(RT-qPCR). Additionally, the protein expression levels of matrix metalloprotein-9(MMP-9)and tissue inhibitor of metalloproteincise 1(TIMP-1)in lung tissue were assessed using blot analysis.Results:The degree of lung fibrosis was significantly reduced in mice in group P compared with group M when treated with bacterial lysis products.Group M showed a significant decrease in the expression of CD4+ T cells and an increase in the expression of CD8+ T cells( P<0.05)compared to group N. Additionally, the content of IgA was decreased( P<0.05)in group M. On the other hand, group P showed a significant increase in the expression of CD4+ T cells and a decrease in the expression of CD8+ T cells( P<0.05)compared to group M. Furthermore, the content of IgA was elevated( P<0.05)in group P. After bacterial lysis product intervention, mRNA and protein expression levels of IFN-γ were elevated( P<0.05), while mRNA and protein expression levels of IL-13 were reduced( P<0.05). Moreover, protein expression of MMP-9 and TIMP-1 was significantly up-regulated in group M compared with group N( P<0.05), and decreased after bacterial lysis product intervention( P<0.05). Conclusions:It is well-known that immune mechanisms play a crucial role in the development of pulmonary fibrosis.The use of bacterial lysates has been found to effectively regulate immune balance and mitigate the severity of pulmonary fibrosis in elderly mice.

17q12 deletion syndrome is a rare autosomal dominant disorder affecting multiple organ systems caused by the deletion of DNA fragments approximately 1.4～1.8 Mb in band 2 of region 1,the long arm of chromosome 17,including hepatocyte nuclear factor 1B.The clinical manifestation of the disease ismaturity-onset diabetes of youth type 5,abnormalities in renalstructure or function,as well as in neurodevelopment or psychiatric systems.

Objective To study the expression of SWI/SNF-related,matrix-associated,actin-depend-ent regulator of chromatin,subfamily A,member 4(SMARCA4)/Brahma-related gene 1,V-raf murine sarco-ma viral oncogene homolog B(BRAF),P53,programmed cell death protein-1(PD-1),and programmed death-ligand 1(PD-L1),and changes in the expression of BRAF and neurotrophic tyrosine receptor kinase(NTRK)in the patients with colorectal cancer in Tibet,thereby providing a basis for targeted therapy and immunotherapy for this disease in Tibet.Methods A total of 64 patients with colorectal cancer resected in the Tibet Autonomous Region People's Hospital from January 2015 to July 2021 were enrolled in this study.The expression of SMARCA4,BRAF,P53,PD-1,and PD-L1 was detected by immunohistochemical staining.The gene fusion involving NTRK1,NTRK2,and NTRK3 was detected by fluorescence in situ hybridization,and the BRAF V600E gene mutation by polymerase chain reaction.Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of(56.59±13.27)years.The tumors were located in the co-lon in 46(71.88%)patients and in the rectum in 18(28.12%)patients.Sixty(93.75%)patients presented adenocarcinoma,and 4(6.25%)patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n =11)and 82.81%(n =53),respectively.Lymph node metastasis occurred in 24(37.50%)patients.The immunohistochemical staining results showed partially down-regulated or absent ex-pression of SMARCA4 in 1(1.56%)patient,positive BRAF expression in 4(6.25%)patients,and mutant expression of P53 in 35(54.69%)patients.The PD-1-expressing tumor associated immune cell was proportion score<10%in 45(70.31%)patients and≥10%in 19(29.69%)patients.The PD-L1 combined positive score was<10 in 52(81.25%)patients and≥10 in 12(18.75%)patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%)patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/mic-rosatellite instability-high(MSI-H)and the PD-1 expression(χ2 = 10.223,P = 0.001;χ2 = 11.979,P = 0.001).Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunothera-py.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To understand the prevalence and characteristics of Rhinovirus (HRV) infection in influenza-like Illness (ILIs) patients in Mianyang, Sichuan province, China.Methods:Throat swabs were collected from patients of ILIs in sentinel hospitals in Mianyang during 2021—2022. Real-time fluorescence quantitative PCR was used to detect 16 common pathogens. The VP4/VP2 coding region genes of HRV positive samples were amplified by nest PCR. The phylogeny, consistency and amino acid variation of different serotypes were analyzed and compared with reference sequences from GenBank database.Results:A total of 332 ILIs′ samples were collected with a virus detection rate of 58.73% (195/332) in Mianyang. Among them, 23 samples (23/332) were HRV-positive, and 18 VP4/VP2 sequences of HRV strains were successfully amplified. It was found that 13 HRV serotypes were detected in ILIs samples in Mianyang, which belonged to three genotypes, namely HRV-A (12 strains), HRV-B (5 strains) and HRV-C (1 strain).Conclusions:HRV was one of the pathogens of ILIs cases in Mianyang during 2021—2022, with HRV-A types as the dominant strains.