In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Objective： To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood therapy for the treatment of diabetic mellitus erectile dysfunction. Methods： China National Knowledge Infrastructure(CNKI), Wanfang Data, VIP, Chinese Biomedical Database(CBM), PubMed, Cochrane Library, Embase and Web of Science were searched from inception until October 20th of 2024，for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of diabetic erectile dysfunction. Literature screening, quality evaluation, and data extraction were carried out in accordance with relevant standards. The software of RevMan5.4 was used for the analysis of publication bias. And meta-analysis was conducted to assess the impact of this therapy on IIEF-5, total effective rate, adverse reactions. The evidence levels according to the analysis results were evaluated. Results: Totally 19 RCTs were included, involving 1 612 patients. The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores (MD=3.59，95%CI［2.14，5.03］，P<0.01)，total effective rate (OR=4.30，95%CI［3.29，5.32］，P<0.000 01）. However, there was no statistically significant difference in the incidence of adverse reactions(OR=0.98，95%CI［0.48，2.01］，P=0.96) between the two groups. Conclusions： Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction. But considering the limited quantity of included studies, more high-quality studies still be needed to validate the therapeutic effect.
Humans ; Male ; Erectile Dysfunction/therapy* ; Randomized Controlled Trials as Topic ; Kidney ; Medicine, Chinese Traditional ; Diabetes Complications/therapy*

OBJECTIVE: To study bioactive compounds from the endophytic fungus Penicillium sp. HJT-A-6 isolated from stem of Rhodiola tibetica, and evaluate its allelopathic activity. METHODS: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. In addition, the allelopathic activity of compound 1 was evaluated by measuring the seed germination rate of R. tibetica. RESULTS: Two new polyketides 4-hydroxy-3,6-dimethyl-2H-pyran-2-one (1) and penilactone E (2), together with six known compounds walterolactone A (3), 5-hydroxyhexan-4-olide (4), 3-methyl-2-penten-5-olide (5), chaetoquadrin F (6), (Z)-6-acetyl-3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (7) and 4-hydroxy-3-(4-hydroxyhexanoyl)-5-methylfuran-2(5H)-one (8) were isolated from Penicillium sp. HJT-A-6. Compound 1 showed moderate seed-germination-promoting activity at a concentration of 0.001 mg/mL while inhibiting the seed germination at concentrations of 0.1 and 0.01 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compound 1 could extend the seed-germination period of R. tibetica (up to 11 d). CONCLUSION Two new compounds were isolated from R. tibetica endophytic fungus Penicillium sp. HJT-A-6. Compound 1 displayed plant hormone-like activity, which inhibited the seed germination of the host plant at high concentrations and promoted the seed germination of the host plant at low concentrations. The results not only enrich the chemical constituents of the endophytic fungi isolated from Rhodiola tibetica, but also provide a theoretical basis for understanding the interaction mechanism between Rhodiola tibetica endophytic fungi and the host plant.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective:The purpose of this study is to explore in depth the mechanism of the impact of brain drain on organizational cohesion,with a view to cracking the vicious circle problem caused by brain drain in the northeast region and eliminating the unfavorable factors affecting the core cohesion of public health institutions.Methods:A combination of convenience sampling and snowball sampling was used to survey11 912 valid questionnaires,and the data were systematically analyzed using descriptive statistics,regression analysis,and moderated mediated effects analysis.Results:Brain drain has a significant negative effect on organizational cohesion(β=-1.29,P<0.001);and role overload partially mediates between the two,with a significant mediating effect(effect value=-0.56,95%CI=-0.67～-0.46),and the indirect effect accounts for 43.4%of the total effect;and monthly income significantly moderates the effect of brain drain on organizational cohesion through role overload(β=1.00,P<0.001).Conclusion:It is recommended to alleviate the sense of role overload among public health personnel by adjusting the level of salary and benefits,and to reduce the negative impact of brain drain by adopting long-term incentive mechanisms and other strategies,thus enhancing organizational cohesion and providing theoretical and practical guidance for relevant institutions.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

Objective To investigate the effects of the Bushen Quhan Huashi Prescription(mainly composed of Drynariae Rhizoma,Eucommiae Cortex,Dipsaci Radix,Notopterygii Rhizoma et Radix,Zingiberis Rhizoma Recens,Coicis Semen,and Achyranthis Bidentatae Radix)in combination with Methotrexate on the disease activity and serum core-binding factor a1(Cbfa1)level of patients with ankylosing spondylitis(AS)of kidney deficiency and governor-vessel cold type.Methods Ninety AS patients with kidney deficiency and governor-vessel cold type were randomly divided into a trial group and a control group,with 45 patients in each group.The control group was given Methotrexate treatment,and the trial group was treated with Bushen Quhan Huashi Prescription on the basis of treatment for the control group.The course of treatment in the two groups lasted for 3 months.The changes of Bath ankylosing spondylitis disease activity index(BASDAI)scores,Bath ankylosing spondylitis function index(BASFI)scores and serum levels of Cbfa1,type I collagen carboxy-terminal peptide(CTX-Ⅰ)and Dickkopf1 protein(DKK1)of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse effects were compared between the two groups.Results(1)After 3 months of treatment,the total effective rate of the trial group was 97.78%(44/45)and that of the control group was 82.22%(37/45).The intergroup comparison by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the disease activity scores of BASDAI and BASFI in the two groups of patients were significantly decreased compared with those before treatment(P＜0.05),and the trial group's reduction of BASDAI scores and BASFI scores were significantly superior to those of the control group,and the differences were statistically significant(P＜0.01).(3)After treatment,the serum levels of serological indicators of Cbfa1,CTX-Ⅰ,and DKK1 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of Cbfa1,CTX-Ⅰ and DKK1 levels in the trial group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).(4)During the treatment,the incidence of adverse reactions in the trial group was 6.66%(3/45)and that in the control group was 11.11%(5/45),and the difference of the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Bushen Quhan Huashi Prescription combined with Methotrexate exerts certain effect in treating AS patients with kidney deficiency and governor-vessel cold type,and the therapy can effectively control the disease activity and reduce the level of serum Cbfa1 expression in the patients.