Cosmetics may be an important source of human exposure to per-and polyfluoroalkyl substances(PFASs),posing risks to human health.In this study,a nontarget screening method for PFASs in cosmetics was developed using ultra-high performance liquid chromatography-high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)based on the Kendrick mass defect(KMD).The sample was extracted by ultrasonic assisted extraction prior to being analyzed by UHPLC-Q-Orbitrap HRMS.Acquisition of HRMS data was achieved in both full scan and data-dependent(Full MS/dd MS2)mode.The data collected by HRMS were imported into an in-lab built R script for processing.Samples retained the mass spectra peaks with KMD values in the range of 0.85-1 or 0-0.15 for in-and out-of-library matching;when KMD deviation(δKMD)<0.001 and CF 2 mass error(δMS)<15 ppm,it was considered as a potential PFASs homologues.According to matches of parent ions(MS),fragment ions(MS2)and retention time(RT)with the in-house built PFASs database,the screened and identified potential PFASs were categorized to 5 confidence levels(CL1-CL5).A total of 15 kinds of PFASs homologues with confidence level of CL3 and above were screened from 13 cosmetics products and 8 cosmetic raw materials,including perfluoroalkyl alcohol,hydroperfluoroalkyl sulfonic acid,chloroperfluoroalkyl sulfonic acid,etc.with concentrations ranging from 1.9 ng/g to 98.1 ng/g.The nontarget screening method could be used to screen and identify PFASs homologues feasibly and therefore provided data basis for management and control of PFASs addition in cosmetics.

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective To analyze the differences and correlations of imaging parameters in patients with Parkinson's disease(PD)combined with cerebral small vessel disease(CSVD)with different cognitive functions based on MRI.Methods A retrospective selection was conducted on 192 PD patients combined with CSVD.According to the Montreal cognitive assessment(MoCA)and mini-mental state examination(MMSE)scores,they were divided into cognitive impairment PD group(n=69)and cognitive normal PD group(n=123),and the clinical data and MRI imaging parameters of the two groups were compared.Results The age and drinking history of the cog-nitive impairment PD group were higher than those of the cognitive normal PD group(P<0.05);the lacune of presumed vascular origin(LPVO)score,periventricular white matter hyperintensity(PVWMH)score,basal ganglia-perivascular space(BG-PVS)score,brain atrophy(BA)score,and CSVD total score in the cognitive impairment PD group were higher than those in the cognitive normal PD group(P<0.05),while there was no statistically significant difference in deep white matter hyperintensity(DWMH)score,cen-trum semiovale perivascular space(CS-PVS)score,and cerebral microbleed(CMB)score between the two groups(P>0.05);Multi-variate logistic analysis showed that age,LPVO score,BG-PVS score,BA score,and CSVD total score were independent influencing factors of cognitive impairment(P<0.05).Conclusion There are differences in imaging parameters such as LPVO score,PVWMH score,BG-PVS score,BA score,and CSVD total score among PD patients combined with CSVD with different cognitive functions,and they are correlated with MMSE and MoCA scores.

Objective To analyze the differences and correlations of imaging parameters in patients with Parkinson's disease(PD)combined with cerebral small vessel disease(CSVD)with different cognitive functions based on MRI.Methods A retrospective selection was conducted on 192 PD patients combined with CSVD.According to the Montreal cognitive assessment(MoCA)and mini-mental state examination(MMSE)scores,they were divided into cognitive impairment PD group(n=69)and cognitive normal PD group(n=123),and the clinical data and MRI imaging parameters of the two groups were compared.Results The age and drinking history of the cog-nitive impairment PD group were higher than those of the cognitive normal PD group(P<0.05);the lacune of presumed vascular origin(LPVO)score,periventricular white matter hyperintensity(PVWMH)score,basal ganglia-perivascular space(BG-PVS)score,brain atrophy(BA)score,and CSVD total score in the cognitive impairment PD group were higher than those in the cognitive normal PD group(P<0.05),while there was no statistically significant difference in deep white matter hyperintensity(DWMH)score,cen-trum semiovale perivascular space(CS-PVS)score,and cerebral microbleed(CMB)score between the two groups(P>0.05);Multi-variate logistic analysis showed that age,LPVO score,BG-PVS score,BA score,and CSVD total score were independent influencing factors of cognitive impairment(P<0.05).Conclusion There are differences in imaging parameters such as LPVO score,PVWMH score,BG-PVS score,BA score,and CSVD total score among PD patients combined with CSVD with different cognitive functions,and they are correlated with MMSE and MoCA scores.

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Objective To investigate the effects of Chaihuang Yishen Granules on renal fibrosis in unilateral ureteral obstruction(UUO)mice and its underlying mechanisms.Methods Twenty-four 8-week-old male C57BL/6 mice were randomly divided into control group,model group,and low and high dose groups of Chaihuang Yishen Granules(6 in each group).In control group,only right kidney ureter was exposed and dissected.In model group,the UUO animal model was established by UUO.In low and high dose groups,mice were administered intragastrically at doses of 3.8 and 7.6 g/kg of Chaihuang Yishen Granules respectively,following the model group's method to establish the UUO model.After 7 days,the mice were euthanized and renal samples were collected.HE and Masson staining were used to observe pathological changes and fibrosis degree of the kidneys in each group,Sirius red staining was used to observe collagen deposition.The expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),type Ⅰ collagen(Col-Ⅰ),glycogen synthase kinase 3β(GSK-3β),and β-catenin related proteins were detected using Western blotting.Changes in A33 and GSK-3β,β-catenin mRNA levels were measured by RT-PCR.Additionally,a normal transformed C3H mouse kidney-1(TCMK1)was used as control(normal group);an in vitro fibrosis model was established using TCMK1 stimulated with Transforming Growth Factor-β(TGF-β);and an in vitro drug model was established using TCMK1 treated with serum containing Chaihuang Yishen Granules.A33 was overexpressed in TCMK1 cells using a transfection with an A33 overexpression plasmid,and changes in fibrosis-related indicators and the expression of A33 and GSK-3β,β-catenin mRNA were observed.Results RT-PCR results showed that,compared with control group,A33 level was significantly increased in model group,while it was significantly reduced in both low and high dose groups of Chaihuang Yishen Granules(P＜0.05).Western blotting showed that the expression levels of fibrosis-related factors such as α-SMA,FN,Col-Ⅰ in model group were significantly higher than those in control group(P＜0.05);while compared with model group,the expression levels of α-SMA,FN,Col-Ⅰ in low and high dose groups of Chaihuang Yishen Granules were significantly lower(P＜0.05).HE,Masson,immunohistochemical staining results showed that model group had severe kidney structural damage,significant increase in collagen deposition,and significantly higher expression levels of GSK-3β and β-catenin proteins compared with those in control group(P＜0.01).In contrast,low and high dose groups of Chaihuang Yishen Granules had good kidney structure,significant improvement in kidney damage and fibrosis,and significantly lower expression levels of GSK-3β and β-catenin proteins compared with those in model group(P＜0.05).In vitro experiment results confirmed that,compared with normal group,A33 overexpression promoted the upregulation of fibrosis-related factors in TCMK1 cells,significantly increase the expression of downstream target genes GSK-3β and β-catenin mRNA in the Wnt/β-catenin signaling pathway(P＜0.05),and A33 overexpression reversed the cellular fibrosis changes downregulated by the serum containing Chaihuang Yishen Granules(P＜0.01).Conclusion Chaihuang Yishen Granules significantly improve renal fibrosis in UUO mice by downregulating the A33/Wnt/β-catenin signaling pathway,suggesting that A33 may be a potential therapeutic target for renal fibrosis.

Objective To explore the relationship between the levels of peroxidoredoxin(PRDX)1 and chromosome 10 deletion phosphatase-tensin homologous gene(PTEN)and liver function and disease activity in patients with autoimmune liver disease.Methods A total of 83 patients with autoimmune liver disease ad-mitted to the hospital from January 2021 to December 2022 were selected as the study objects.According to the disease activity at admission,they were divided into active group(37 cases)and remission group(46 ca-ses).Clinical data and serum PRDX1 and PTEN levels of the two groups were analyzed.At the same time,Child-Pugh classification of liver function was performed,and the patients were grouped.A total of 100 health-y volunteers who underwent physical examination during the same period were selected as the control group.Multivariate Logistic regression was used to analyze the influencing factors of disease activity in patients with autoimmune liver disease,and the evaluation value of serum PRDX1 and PTEN levels on disease activity in pa-tients with autoimmune liver disease after treatment was analyzed by receiver operating characteristic(ROC)curve and area under the curve(AUC).Results Compared with the grade A group,there were no significant differences in serum PRDX1 and PTEN levels in the grade B group(P＞0.05),while serum PRDX1 level was increased and PTEN level was decreased in the grade C group(P＜0.05).Compared with the grade B group,the serum PRDX1 level was increased and PTEN level was decreased in the grade C group(P＜0.05).Com-pared with the control group,there were no significant differences in serum PRDX1 and PTEN levels in the re-mission group(P＞0.05),while the serum PRDX1 level was increased and PTEN level was decreased in the active group(P＜0.05).Compared with the remission group,the level of serum PRDX1 was increased and the level of PTEN was decreased in the active group(P＜0.05).The AUC of serum PRDX1 and PTEN for evalu-ating the disease activity in autoimmune liver disease patients was 0.750 and 0.854,respectively,and the AUC of the combined detection of serum PRDX1 and PTEN was 0.916.The proportion of patients with hepatic dis-comfort and cirrhosis in the active stage group was higher than that in the remission stage group(P＜0.05).Multivariate Logistic stepwise regression analysis results showed that hepatic discomfort(OR=3.487,95％CI:1.534-7.927),cirrhosis(OR=4.289,95％CI:1.744-10.545),PRDX1 ≥5.22 ng/mL(OR=5.068,95％CI:1.951-13.164),PTEN≤0.31 pg/mL(OR=5.387,95％CI:2.099-13.829)were risk factors for disease activity of autoimmune liver disease(P＜0.05).Conclusion The increase of serum PRDX1 level and the decrease of serum PTEN level are closely related to liver function and disease activity in patients with au-toimmune liver disease,and they have certain clinical evaluation value in patients with autoimmune liver dis-ease.