OBJECTIVE: To investigate cisplatin-induced cardiovascular toxicity and explore the protective effects and potential mechanism of curcumin co-treatment. METHODS: Forty adult male Sprague-Dawley rats were numbered and randomly divided into control group, cisplatin group (7.5 mg/kg, once a week, for 2 weeks), curcumin group (200 mg/kg per day, for 2 weeks) and cisplatin+curcumin group (cisplatin 7.5 mg/kg, once a week, and curcumin 200 mg/kg per day for 2 weeks) by a random number table method, with 10 rats in each group. Cardiac and vascular morphology and functions were assessed using hematoxylin-eosin and Masson's trichrome staining, serum indexes detection, echocardiography, electrocardiogram (ECG), blood pressure monitoring, vascular ring isometric tension measurement, and left ventricular pressure evaluation. The expressions of extracellular signal-regulated kinases (ERK) and phosphorylated-ERK (p-ERK) were analyzed by immunohistochemical staining. RESULTS: Cisplatin treatment induced notable cardiac alteration, as evidenced by changes in cardiac morphology, elevated serum enzymes (P<0.05), ECG abnormalities, and increased left ventricular end-diastolic pressure (P<0.05). Meanwhile, cisplatin significantly increased arterial pulse pressure (P<0.01), primarily due to a decrease in diastolic blood pressure. Severe fibrosis was also observed in the thoracic aorta wall. In vascular ring experiments, cisplatin treatment led to a significant reduction in phenylephrine-induced contraction (P<0.05) and acetylcholine-induced relaxation (P<0.01). Notably, Curcumin co-administration significantly alleviated cisplatin-induced cardiovascular damages, as demonstrated by improvement in these parameters. Furthermore, ERK expression in the myocardium and p-ERK expression in vascular smooth muscle cells were significantly upregulated following curcumin co-treatment. CONCLUSIONS Curcumin protects the heart and vasculature from cisplatin-induced damages, likely by upregulating ERK/p-ERK expression. These findings suggest that curcumin may serve as a promising therapeutic strategy for mitigating cisplatin-associated cardiovascular toxicity during tumor chemotherapy. In vitro cell culture experiments are needed to clarify the underlying mechanism.
Animals ; Curcumin/therapeutic use* ; Cisplatin/adverse effects* ; Rats, Sprague-Dawley ; Male ; Up-Regulation/drug effects* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Phosphorylation/drug effects* ; Electrocardiography ; Blood Pressure/drug effects* ; Rats ; MAP Kinase Signaling System/drug effects*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

AIM:To evaluate the application effect of artificial intelligence(AI)assisted diagnosis system in screening diabetic retinopathy(DR)in Yinchuan Community, Ningxia Hui Autonomous Region.METHODS:From July 2020 to July 2021, fundus photograph of 2 707 eyes from 1 358 diabetic patients with type 2 diabetes in two communities of Ningxia and Yinchuan were included in this study. The Eye Wisdom AI assisted screening and diagnosis system was used to analyze automatically and detect the characteristic changes of DR, such as hemorrhage, microaneurysms and retinal microvascular abnormalities. The results of fundus photograph were automatically graded according to the standard of DR international stage standard. The manual analysis group gave feedback after image interpretation, analyzed the sensitivity, specificity, misdiagnosis rate and missed diagnosis rate of the AI-assisted screening system for DR diagnosis, and compared the consistency between AI and manual analysis. Kappa consistency test was performed for the results of AI screening system and manual analysis.RESULTS:Compared with manual analysis, the sensitivity, specificity, missed diagnosis rate and misdiagnosis rate of AI were 91.84%, 99.06%, 8.16% and 0.94% respectively. The Kappa value of consistency analysis of the two diagnosis results was 0.817(P<0.001). Compared with manual analysis, the sensitivity and specificity of AI group to diagnose non-DR were 99.06% and 91.84% respectively. The sensitivity and specificity of mild NPDR were 85.36% and 98.52% respectively. The sensitivity and specificity of moderate NPDR were 81.53% and 98.55% respectively. The sensitivity and specificity of severe NPDR were 70% and 99.51% respectively. The sensitivity and specificity of PDR were 86.67% and 99.63% respectively. The Kappa value of the consistency analysis of DR staging diagnosis was 0.878(P<0.01).CONCLUSION: The AI remote screening system adopted in this study showed good consistency with the results of manual analysis, which can meet the needs of DR screening and provide a new effective prevention and treatment mode for DR patients in the community.

OBJECTIVE: To prepare and develop a GDH-2 air sampling tube for detecting 12 kinds of chlorobenzenes(CBs) in workplace air and to establish a matching detecting method. METHODS: The self-developed GDH-2 air sampling tube was filled with ion exchange resin and activated carbon, and the mass ratio was 10 ∶1. The GDH-2 air sampling tube was used to collect 12 kinds of CBs with coexistence of gaseous and aerosol in the air. After elution with toluene, they were separated on a chromatographic column and determined by microcell electron capture detector. RESULTS: The quantitative detecting range of the method was 0.51×10~(-3)-6 000.00 mg/L, with the correlation coefficients greater than 0.999 4. The minimum detection concentration was 0.02-61.99 μg/m~3, and the minimum quantitative concentration was 0.05-206.62 μg/m~3. The average desorption efficiency was 90.8%-104.0%. The within-run relative standard deviation(RSD) was 1.0%-5.7%, and the between-run RSD was 3.0%-7.3%. The samples can be stored at room temperature for at least 26 days. CONCLUSION: The self-developed GDH-2 air sampling tube and its matching measuring method can be used for the collection and determination of the 12 kinds of CBs in the air of workplace.

Objective: In order to elucidate the biological activity of the co-cultured adventitious roots (ARs) of Echinacea pallida and Echinacea purpurea and provide theoretical basis for its application, and the anti-inflammatory activities and potential mechanisms of co-cultured ARs were studied. Methods: The experimental materials were obtained by bioreactor co-culture technology and used in the activity research. In this study, mouse macrophages induced by lipopolysaccharide (LPS) were used as in vitro model. Different concentrations of AR extract (50–400 g/mL) were used to treat cells. The expression of pro-inflammatory cytokines was determined using enzyme linked immunosorbent assay. The inducible nitric oxide synthase and cyclooxygenase-2 expression, mitogen-activated protein kinase (MAPK) phosphorylation, and the inhibitor of nuclear factor-kappa B-α levels were determined by the Western blot analysis. Results: In the co-cultured ARs, total flavonoids and total caffeic acid were determined, and the contents of both bioactive compounds were significantly higher than those ARs from the single-species culture. Compared with the control group, the large amount of pro-inflammatory mediators was released after LPS stimulation. However, in the extract groups with different concentrations (25, 50, and 100 g/mL), the production of these pro-inflammatory mediators was inhibited in a dose-dependent manner. Furthermore, the levels of phosphorylation of MAPK proteins, including p-p38, p-c-Jun N-terminal kinase, and p-extracellular regulated protein kinases were significantly (P < 0.05) decreased in the extract groups, revealing that the AR extract probably involved in regulating the MAPK signaling pathway. Conclusion: Collectively, our findings suggested that the co-cultured ARs of E. pallida and E. purpurea can inhibit production of pro-inflammatory mediators in mouse peritoneal macrophages and possess the anti-inflammatory effect by regulating MAPK signaling pathways.

Objective To explore the establishment of a two-way referral system for the treatment of cervical diseases within a medical alliance. The two-way referral system was introduced to reduce the morbidity and mortality of cervical cancer through better management of patients'who have tested positive for cervical disease, screening effectively for early diagnosis and treatment of cervical precancerous lesions, and providing early interventions for cervical cancer patients. Methods The control group consisted of 2, 515 patients who had screened positive for cervical disease between January 2018 and December 2018 at one of four community health service centers that were not within the medical alliance. The experimental group consisted of 2, 384 patients who had screened positive for cervical disease at one of four community health service centers in the medical alliance. The control group was treated using the original management mode;the experimental group's treatment was managed within the two-way referral system, which included standardized screening, referral, follow-up, health education, and professional training. The hospital visit rates, time intervals from diagnosis to the start of interventions, detection rates, and treatment rates were observed for both groups of women. Results The hospital visit rates, detection rates, and treatment rates were higher for those in the experimental group than the control group. The time interval from receiving a diagnosis to the first hospital visit was (16.9±11.5) days for patients in the experimental group and (25.7±20.9)days for those in the control group. The difference was a statistically significant (-0.05). Conclusion The management of cases in a two-way referral system within a medical alliance facilitates patients receiving earlier diagnosis and treatment for cervical pre-cancerous lesions and malignant tumors. Such efficiency improvements may reduce morbidity and mortality as well as help control medical costs, all of which have long-term economic and social significance.

Aim To investigate whether polydatin re-duces airway inflammation in asthmatic mouse model and explore whether this pathway is related to p38 MAPK/Nrf2/HO-1 . Methods After the establish-ment of the OVA-induced asthmatic mouse model, the animals were injected with 30 mg·kg-1 and 45 mg· kg-1 of polydatin diluted in 0. 2 mL normal saline, while the control group was replaced by normal saline. HE, PAS and Masson staining were used to observe the pathological changes of lung tissue. Diff-Quick staining was used to classify and count the number of inflamma-tory cells in BALF. ELISA was used to detect IgE ex-pressions in BALF. The content of ROS in BALF cells was detected by DHR-123 . The activities of antioxidant enzymes SOD, CAT and MDA in BALF were detected by the enzyme-linked immunosorbent assay kit. The expression of HO-1 in lung tissue was detected by im-munohistochemistry. The protein and mRNA expres-sions of Nrf2 and HO-1 in lung tissue of mice were de-tected by Western blot and RT-PCR. Results Poly-datin treatment significantly reduced inflammatory cell infiltration mucosal secretion, goblet cell proliferation and collagen deposition in the lung tissue of mice, and decreased the number of inflammatory cells and the ex-pression of total IgE and ROS in BALF. It also in-creased the levels of antioxidant enzymes such as SOD and CAT, and lowered the level of MDA. Polydatin re-duced the phosphorylation of p38 MAPK in the lung tissue of mice, enhanced the levels of mRNA and pro-tein expressions of Nrf2 and HO-1 and promoted the nuclear transfer of Nrf2 . The above effects of polydatin were dose-dependent. Conclusions Polydatin exerts anti-oxidative effects in OVA-induced asthmatic mouse model via anti-oxidant pathway. The mechanism may be achieved through the p38 MAPK/Nrf2/HO-1 path-way.

To intuitively understand the phenotypic diversity of intra-population and inter-population of the medicinal Cistanche Herba distributed in Xinjiang province, three species of Cistanche Herba were selected for the first time to be conducted to phenotypic observation and measurement from the morphological perspective, aiming to fill the gap in the morphological research concerning Cistanche Herba, and discuss about the relationship between the phenotypic variation and the host plants together with the geographical conditions, thus better understanding the speciation and evolutionary mechanism of Cistanche Herba and providing some scientific basis for the resource protection and germplasm breeding of Cistanche Herba. Based on sampling survey, a total of 118 well grown medicinal Cistanche samples from 17 Cistanche Herba distribution areas in Xinjiang province were selected, and various indexes were observed and measured. Besides, ANOVA and clustering analysis were conducted with 9 phenotypic quantity characters. The Cistanche Herba was plentiful in phenotypic variation. For detail, significant intra-population differences were observed in eight of the nine character indexes, and the intra-population differences were more obvious than those of inter-population. For each quantity character of the three species, the flower density possessed the maximal variable coefficient (71.1%) while the flower length was the minimum (15.9%). The phenotypic variation was also obvious among different populations. Specifically, the average variable coefficient of flower number was the maximal one (46.5%) and the flower length was the minimum one (10.0%). For different populations, the average variable coefficient of the D4 population was the maximal one (41.1%) and the S3 population was the minimum one (13.5%). According to the clustering analysis, all the samples of Cistanche Herba could be divided into three groups when the Euclidean distance was set at 15. The populations of S1, S3, D1, S2, D4, D6, D7 and D5 which distributed in the north of Xinjiang were clustered into one group, and the populations of D8, S4, D9, D2 and D3 that grown in east and central of Xinjiang were clustered into another group. The populations of C. deserticola and C. salsa could not be completely separated, but both of them were obviously differentiated from the T1, T3 and T2 populations of C. tubulosa. Besides, the C. deserticola and C. salsa displayed a patch distribution among different populations, and similar phenotypic characters were shared for each population. The research results of phenotype were consistent with that of molecular biology study of Cistanche Herba. The different phenotypic characters in different distribution areas were deduced to be arose from geographical isolation caused by mountains, which led to the specific genetic structure for each population of Cistanche Herba during the long-term adaptation and evolution. In conclusion, the current study showed the adaptation potency of Cistanche Herba exposed to different habitats.
China ; Cistanche ; classification ; Cluster Analysis ; Ecosystem ; Flowers ; Genetics, Population ; Phenotype ; Plants, Medicinal ; classification

Lagerstroemia speciosa Pers,also known as banaba,belongs to Lythraceae and contains ursolic acid,corosolic ac?id,asiatic acid and 30 other kinds of effective components.It has multiple pharmacological activities,including hypoglycemic,hypo?lipidemic,anti-oxidant and anti-viral activities,and is mainly used for the treatment of obesity and diabetes in folk medcine.This re?view summarizes the recent advances in chemical composition and pharmacological effects of L.speciosa Pers,so as to provide the theo?retical basis and reference for its further research and application.

OBJECTIVETo determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3b (GSK3b) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3b on inflammation mediated by Toll-like receptor 4 (TLR4).

METHODSC57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia, followed by reperfusion for various lengths of time. The mice were divided into three groups: the H-IR untreated model (control group), and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3b-specific inhibitor (intervention group). To create a parallel isolated cell system for detailed investigations of macrophages, marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages. The cells were then divided into the same three groups as the whole mouse system: control, LPS-induced inflammation model, and inflammation model with SB216763 intervention. Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR, respectively.

RESULTSThe phosphorylation levels of ERK, JNK and p38 MAPK were induced in liver at 1 h after reperfusion, but then steadily decreased and returned to baseline levels by 4 h after reperfusion. In addition, the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation, while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK, JNK and p38 phosphorylation in macrophages. In the mouse model, GSK3b activity was found to promote the gene expression of anti-inflammatory cytokine IL-10 (control: 0.21 ± 0.08, inflammation: 0.83 ± 0.21, intervention: 1.76 ± 0.67; F = 3.16, P = 0.027) but to significantly inhibit the gene expression of pro-inflammatory cytokines IL-12 (control: 0.11 ± 0.05, inflammation: 0.85 ± 0.11, intervention: 0.43 ± 0.10; F = 2.67, P = 0.038), TNF-a, (control: 0.052 ± 0.012, inflammation: 8.11 ± 0.98, intervention: 3.9 ± 0.82; F = 4.13, P = 0.016), IL-6 (control: 0.22 ± 0.08, inflammation: 6.37 ± 0.81, intervention: 2.11 ± 0.63; F = 3.21, P = 0.024), and IL-1b (control: 0.12 ± 0.07, inflammation: 2.51 ± 0.62, and intervention: 1.28 ± 0.33; F = 2.22, P = 0.030).

CONCLUSIONInhibition of GSK3b selectively regulates the expression of anti-inflammatory and pro-inflammatory cytokines in liver Kupffer cells (liver macrophages). This process may be one of the mechanisms underlying the ability of GSK3b to ameliorate hepatic ischemia-reperfusion injury, possibly because inhibition of pro-inflammatory cytokines may indirectly mediate liver cell apoptosis.

Animals ; Cells, Cultured ; Cytokines ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Liver ; pathology ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; Toll-Like Receptor 4 ; metabolism