Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

Objective To investigate the role of long non coding RNA(lncRNA)Gm14461 in promoting trigeminal neuralgia(TN)and its potential molecular mechanisms.Methods A TN mouse model was induced by surgery for chronic compression injury of the infraorbital nerve.Short hairpin RNA(shRNA)of Gm14461 was injected into TN mice,and the expression level of Gm14461 and mechanical pain threshold(MWT)in the trigeminal ganglia of the mice were measured.A TN cell model was established in vitro using tumor necrosis factor-α(TNF-α)to induce trigeminal ganglia,and the trigeminal ganglia were treated with sh-Gm14461 and cleavage stimulation factor subunit 2(CSTF2)overexpression vector(OE-CSTF2).RNA immunoprecipitation(RIP)analysis of CSTF2 binding to Gm14461,calcitonin gene-related peptide(CGRP),purine receptors P2X3 and P2X7 mRNA.Results Compared with the sham surgery group,the expression of Gm14461 in the trigeminal ganglia of TN group mice was significantly increased(t=35.450),and the MWT value of mice decreased in a time-dependent manner(t=8.427～28.190),with statistical significance(all P<0.05).The expression levels of inflammatory factors TNF-α,IL-1 β and IL-6,as well as pain related proteins CGRP,P2X3,and P2X7,were significantly increased in the trigeminal ganglia of TN mice,and the differences were statistically significant(t=31.750～50.240,all P<0.05).Knocking down Gm14461 significantly improved MWT(t=6.019～26.548),reduced inflammatory factors(t=43.959,26.416,25.431),and pain related protein levels(t=38.709,43.257,45.807)in TN mice,with statistically significant differences(all P<0.05).Compared with the control group,TNF-α induced upregulation of Gm14461 expression in the trigeminal ganglia(t=27.710),significantly increased levels of inflammatory factors and pain related protein expression(t=23.076～29.508),and the differences were statistically significant(all P<0.05).After knocking down Gm14461,the expression of Gm14461 was significantly reduced(t=3.641),and the levels of inflammatory factors and pain related proteins in the trigeminal ganglia induced by TNF-α were significantly reduced(t=20.560～25.136),with statistical significance(all P<0.05).Gm14461 upregulates CSTF2 protein levels by binding to CSTF2,and upregulates CSTF2 protein by binding to mRNA of CGRP,P2X3,and P2X7 and promoting their expression.Overexpression of CSTF2 can reverse the inhibitory effect of Gm14461 knockdown on TNF-α-induced inflammation and pain related protein expression in trigeminal ganglia(TGs)(t=18.870～24.399,all P<0.05).Conclusion Gm14461 upregulates the expression of CGRP,P2X3,and P2X7 by recruiting CSTF2,promotes inflammatory response,thereby reducing the mechanical pain threshold of TN mice and promoting pain.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

Objective To investigate the clinical characteristics of colorectal polyps in patients with melanosis coli(MC),analyze the recurrence risk after polypectomy,and construct a prediction model for polyp recurrence.Methods A total of 1,763 patients who underwent colorectal polypec-tomy at the First Hospital of Handan from January 2017 to June 2023 were divided into MC group(n=149)and non-MC group(n=1,614).Among them,122 patients in the MC group underwent colonoscopic re-examination one year later and were further divided into recurrence group(n=52)and non-recurrence group(n=70)based on polyp recurrence.The characteristics of colorectal polyps and recurrence risk after polypectomy in MC patients were analyzed.A multivariable Logistic regression analysis was used to construct a polyp recurrence risk model,and the nomogram model was plotted using R studio software.The receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis were employed to evaluate the discrimination,calibration,and clinical practicality of the model.Results The detection rates of large polyps(≥1.0 cm),right-sided colon polyps,multiple polyps(≥3 polyps),and Yamada type Ⅰ polyps in the MC group were significantly higher than those in the non-MC group,while the detection rates of left-sided co-lon polyps and Yamada type Ⅳ polyps were significantly lower(P＜0.05).The detection rates of adenomatous polyps and polyps with mild dysplasia in the MC group were significantly higher than those in the non-MC group,whereas the detection rate of polyps with moderate dysplasia in the MC group was significantly lower(P＜0.05).Significant differences were observed between the recur-rence and non-recurrence groups in terms of a history of cholecystectomy,Helicobacter pylori(Hp)in-fection,and family history of colorectal cancer(P＜0.05).There were also significant differences in the distribution,size,and the number of initial polyps between the two groups(P＜0.05).Multivari-able Logistic regression analysis identified cholecystectomy,Hp infection,first-degree relatives with colorectal cancer,polyp size(≥1 cm),and multiple polyps(≥3 polyps)as independent risk factors for polyp recurrence after polypectomy(P＜0.05).Based on these factors,a recurrence prediction model was constructed.The area under the curve(AUC)of this model was 0.824(95％CI,0.753 to 0.895),indicating good discrimination.The calibration curve showed a good fit.Decision curve anal-ysis demonstrated a high net benefit within the threshold range of 0.1 to 0.8,suggesting that the mod-el had a wide range of beneficial thresholds and clinical practical value.Conclusion Compared with the non-MC group,the MC group has higher detection rates of large polyps,right-sided colon pol-yps,multiple polyps,Yamada type Ⅰ polyps,adenomatous polyps,and polyps with low-grade dys-plasia,but lower detection rates of left-sided colon polyps,Yamada type Ⅳ polyps,and polyps with moderate dysplasia.Cholecystectomy,Hp infection,first-degree relatives with colorectal cancer,large polyps(≥1 cm),and multiple polyps(≥3 polyps)are independent risk factors for polyp re-currence after colorectal polypectomy in MC patients.The recurrence prediction model constructed based on these factors has high practical value.

Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Objective To identify risk factors for colorectal adenomatous polyps using logistic regression analysis,construct a prediction model based on these identified factors,and subsequently evaluate the performance of the model.Methods Encompassed 1,023 patients who underwent large intestine polyp resection at the First Hospital of Handan between January 2017 and January 2022.Among these patients,676 had adenomatous polyps(adenomatous polyp group)and 347 had non-adenomatous polyps(non-adenomatous polyp group).We collected data on basic information,medical history,colonoscopy results,and polyp pathology.By comparing the two groups,we identified significant differences in various indicators,which were selected as candidate factors for model construction.Patients were randomly divided into a training set and a validation set at an 8∶2 ratio.Using the training set data,we constructed a risk prediction model and developed a nomogram using R Studio software to visually present the model.Finally,we internally validated the model using the validation set.The model's discrimination ability was evaluated using the ROC curve,its accuracy was assessed via the calibration curve,and its clinical utility was evaluated through decision curve analysis(DCA).Results Significant differences were observed between the two groups in terms of age,drinking habits,family history of colorectal cancer,hyperlipid-emia,history of cholecystectomy,HP infection,and history of appendectomy(P<0.05).These variables were included in the model construction.A total of 818 participants were randomly assigned to the training set,while 205 were allocated to the validation set.Multivariate logistic regression analysis on the training set confirmed that age(OR=1.021,95%CI:1.006～1.036,P=0.006),alcohol consumption(OR=3.440,95%CI:2.251～5.257,P<0.001),first-degree relatives with colorectal cancer(OR=3.775,95%CI:1.881～7.577,P<0.001),hyperlipidemia(OR=3.428,95%CI:2.443～4.808,P<0.001),history of cholecystectomy(OR=3.916,95%CI:1.756～8.735,P<0.001),Helicobacter pylori(HP)infection(OR=3.292,95%CI:2.309～4.693,P<0.001),and history of appendectomy(OR=3.819,95%CI:2.002～7.286,P<0.001)were independent risk factors for adenomatous polyps.Consequently,a prediction model for large intestine adenomatous polyps was developed using the formula P=1/(1+e-Y),where Y=0.020×age+1.328×first-degree relatives with colorectal cancer+1.235×alcohol consumption+1.232×hyperlipidemia+1.365×cholecystectomy+1.192×HP infection+1.340×appendectomy-1.995.The model demonstrated good performance with AUC values of 0.763(95%CI:0.729～0.797)for the training set and 0.769(95%CI:0.644～0.787)for the validation set.The calibration curve indicated a good fit,and decision curve analysis showed that the model could achieve positive net benefit across a wide range of threshold probabilities,confirming its clinical utility.Conclusions Age,alcohol consumption,a family history of colorectal cancer in first-degree relatives,hyperlipidemia,cholecystectomy,HP infection,and appendectomy were identified as independent risk factors for adenomatous polyps.A prediction model incorporating these risk factors holds significant practical value for predicting the occurrence of colorectal adenomatous polyps.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.