Objective To develop albumin-binding indocyanine green (ICG) and assess its potential for near-infrared fluorescence imaging and intraoperative navigation in lung cancer. Methods ABD-tri was recombinantly expressed by genetic engineering. Its albumin-binding capability was determined using size-exclusion chromatography, and its albumin-dependent binding to lung cancer cells was evaluated by flow cytometry. ICG was conjugated to ABD-tri to generate the fluorescent probe ABD-tri-ICG. The potential of ABD-tri-ICG for near-infrared fluorescence imaging and imaging-guided tumor resection was evaluated in mice bearing subcutaneous tumor grafts of lung cancer. Results ABD-tri was highly expressed in Escherichia coli (E. coli) and was purified to homogeneity via a simple affinity chromatography. ABD-tri bound both human and murine serum albumin, contributing to its binding to lung cancer cells. ICG was effectively conjugated to ABD-tri to produce the fluorescence probe ABD-tri-ICG after mixing and incubation at room temperature for 1 h. In mice bearing lung cancer tumor grafts, intravenously injected ABD-tri-ICG enabled clear visualization of tumors with diameters ranging from 5 to 7 mm within 0.5-24 h post-injection. The tumor grafts were resected under the guidance of ABD-tri-ICG-mediated near-infrared fluorescence imaging. Conclusion Intravenous injection of ABD-tri-ICG allows rapid and sustained visualization of lung cancer tumor grafts and enables intraoperative navigation in mice, warranting further evaluation on the clinical translation of ABD-tri-ICG.

ObjectiveTo investigate the efficacy and safety of simplified diagnosis and treatment strategies and regimens in the treatment of patients with human immunodeficiency virus （HIV）/hepatitis C virus （HCV） co-infection. MethodsThis multicenter prospective real-world study was conducted among 198 patients with HIV/HCV co-infection who received hepatitis C treatment in 10 designated primary hospitals for hepatitis C in Yuxi， China from July 2023 to June 2024， and according to whether genotype detection was performed， they were divided into genotype detection group with 122 patients and non-genotype detection group with 76 patients. The patients were observed in terms of sustained virologic response at 12 weeks （SVR12）， safety， and liver biochemical parameters. Propensity score matching was used to match the two cohorts， using caliper matching （caliper value = 0.02） at a ratio of 1∶1. The independent-samples t test or the Wilcoxon signed-rank test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 122 patients in the genotype detection group， 63.11% （77/122） had genotype 3， while the non-genotype detection group had 76 patients； both groups achieved an SVR12 rate of 100%. From baseline to 12 weeks after treatment， both groups had a significant increase in the serum level of albumin， significant reductions in the serum levels of total bilirubin， alanine aminotransferase， aspartate aminotransferase， and alpha-fetoprotein， and a significant reduction in FibroScan value （all P<0.05）. A total of 54 patients （27.27%） experienced at least one adverse reaction， and anemia was the most common adverse reaction （38 patients， 19.19%）， with an incidence rate of 50.00% （33/66） in patients with liver cirrhosis. HIV viral load remained <50 IU/mL before and after treatment， and there was no significant change in CD4⁺ T lymphocyte count after treatment （Z=-0.969， P=0.202）. Compared with the genotype detection group， the non-genotype detection group had a significantly shorter time from positive HCV RNA testing to treatment initiation （4±2 days vs 19±4 days， t=5.321， P<0.05） and significantly lower testing costs （618±97 yuan vs 789±129 yuan， t=3.661， P<0.05）. ConclusionFor patients with HIV/HCV co-infection， the simplified diagnosis and treatment strategies can achieve a relatively high SVR12 rate， improve biochemical indicators， and effectively reduce time cost and economic burden， with a favorable safety profile.

Background Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants widely distributed in the environment. Epidemiological studies have shown that PFAS exposure is closely associated with liver dysfunction and an increased risk of liver cancer. Some animal and cell experiments have also revealed its hepatotoxicity and potential carcinogenicity; however, the related carcinogenic mechanism has not yet been fully elucidated. Objective To explore the potential molecular mechanism of PFAS-induced liver cancer, identify the key causal genes, and specifically evaluate the causal association and expression changes of KMT2C in this process, as well as the binding stability between KMT2C and PFAS, and to provid a theoretical basis for mechanistic studies and molecular target discovery in PFAS-related liver cancer. Methods Toxicity prediction was performed on six representative PFAS. Potential target genes of PFAS were identified by integrating results from SwissTargetPrediction, STITCH, and TargetNet databases. Liver cancer-related genes were retrieved from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection of PFAS targets and liver cancer-related genes was used to obtain core genes. A compound-gene-disease regulatory network was constructed, and a protein–protein interaction network was established using STRING database. A core gene network was visualized based on node degree values. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore biological functions and enriched signaling pathways. Subsequently, two-sample Mendelian randomization was employed to assess potential causal relationships between candidate genes and hepatocellular carcinoma, enabling the identification of key genes. Molecular docking analysis using AutoDock was conducted to evaluate the binding stability between KMT2C and PFAS, and TCGA data were used to validate the differential expression of KMT2C between hepatocellular carcinoma and adjacent normal tissues. Results PFAS exhibited multisystem toxicity and posed significant risks of liver injury and carcinogenesis. A total of 266 PFAS target genes and 2923 liver cancer-related genes were identified, with 61 intersecting genes obtained. The enrichment analysis revealed that these intersecting genes were primarily involved in epigenetic regulation, nuclear receptor signaling pathways, and apoptosis-related pathways including TGF-β FoxO and Notch, suggesting their roles in diverse tumor-related biological processes. The two-sample Mendelian randomization results showed a significant negative causal association between KMT2C and hepatocellular carcinoma (OR=0.68, P <0.05). The molecular docking results demonstrated that all tested PFAS exhibited favorable binding to the KMT2C protein, with binding energies below –5.0 kcal·mol⁻¹. KMT2C was significantly upregulated in hepatocellular carcinoma tissues (unpaired P=0.025; paired P=8.38 × 10⁻⁴). Conclusion The KMT2C protein is found to stably bind with all six PFAS, exhibiting strong structural affinity. A causal relationship is identified between KMT2C and the development of hepatocellular carcinoma. TCGA data indicate that KMT2C is significantly upregulated in hepatocellular carcinoma tissues, and it may serve as a key regulatory target in PFAS-related liver cancer.

Time-of-flight secondary ion mass spectrometer(TOF-SIMS)is a highly sensitive surface analysis instrument with high spatial resolution.Traditional TOF-SIMS instruments for sample targets use high field extraction methods.Although the ion collection efficiency is high,it is prone to issues such as low-energy ion beam defocusing,sample morphology sensitivity,and organic molecule ion dissociation.This study aimed to develope an efficient low-field ion extraction system suitable for TOF-SIMS with a continuous beam source.The SIMION simulation software was used to construct a model of the secondary ion optical extraction system.The key factors affecting the extraction efficiency were studied,and the structural parameters of the extraction cone were optimized.Using an indium target as the sample,an experimental test of the performance of the ion extraction system was carried out on the TOF-SIMS instrument.The influences of the voltages of the ion extraction cone and the single lens on the ion extraction efficiency were consistent with the simulation results.By adopting the technology of deflection and coaxial dynamic compensation,the imaging field of view of the ion extraction system was increased to 500 μm×500 μm.The energy window of the ion extraction system reached 10 eV,and the large imaging depth of field of 400 μm was achieved.In the test of a 5 mg/L cholesterol thin film sample,the signal-to-noise ratio of the characteristic peak[M-OH]+reached 4453.The results showed that this low-field secondary ion extraction system effectively improved the performance of the continuous beam TOF-SIMS instrument.

Raynaud syndrome is a clinical syndrome characterized by paroxysmal vasospasms of the acral small arteries,and its pathogenesis is closely associated with the dynamic imbalance of yin and yang as elucidated by the theory of"yang transforming qi and yin shaping up body."The theory of"yang transforming qi and yin shaping up body"originated in Huangdi Neijing,which is aimed at that yang can be tangible essence,blood,fluid,and other substances belonging to the yin into an invisible qi,promote the internal and external zang-fu organs and qi of the body's operation;yin qi is transformed into tangible substances under the gasification effect of yang qi to nourish the organism,to consolidate the essence of internal zang-fu organs,and to maintain the balance of yin and yang in the body.This study innovatively employs this theory to systematically elucidate the dynamic pathomechanism evolution of Raynaud syndrome:at the beginning of the disease,the ischemic stage is dominated by the deficiency of yang qi and the inability of qi to transform yin;then the disease enters into the hypoxic stage and the dilatation stage,which are mostly caused by the lack of yang depression,the blockage of qi,and the over-excessive formation of yin;and finally,the yang transforms qi too much and yin is damaged and weak,and then reaches the stage of complication.In Raynaud syndrome,the key mechanism and pathology of"yang transforming qi"and"yin shaping up body"as well as the stage of the disease should be clarified,so that yang qi can be used as the basis to make up for yang deficiency,yang depression can be stretched out,yin evils such as cold condensation,blood stasis and water dampness can be transformed,heat and toxin can be eliminated,yin fluids can be restored,and the extremities can be warmed up.The disease will be convalesced gradually.

Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical thread was passed through the abdominal aorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg-1;the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg-1;the CVF were(1.95±0.23)％,(2.40±0.25)％,(3.65±0.25)％,(5.43±0.29)％,(6.97±0.36)％and(9.38±0.49)％;the relative expression levels of OPG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P＜0.05).There were positive linear correlation between the relative expression levels of OPG,RANKL,RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure(allP＜0.01).Conclusions In the process of chronic heart failure,the expression of OPG/RANKL/RANK axis is obviously enhanced,in which the up-regulation of RANKL level is most obvious.The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

Objective To investigate the association of Chinese visceral adiposity index(CVAI)and high-sensitivity C-reactive protein(hs-CRP)with the risk of digestive malignancies in the Kailuan study population,and to provide a basis for the prevention and control of digestive malignancies in the population.Methods A prospective cohort study was conducted,and a total of 94 377 Kailuan workers who participated in the 2006 health examination,had no history of cancer,and had complete data on CVAI,CRP,and related covariates were selected as the observation cohort.According to the levels of CVAI and CRP,the subjects were divided into low CVAI+CRP≤3 mg/L group[CVAI(-)CRP(-)group],low CVAI+CRP>3 mg/L group[CVAI(-)CRP(+)group],high CVAI+CRP≤3 mg/L group[CVAI(+)CRP(-)group],and high CVAI+CRP>3 mg/L group[CVAI(+)CRP(+)group].An analysis of variance was used for comparison of normally distributed continuous data between groups,and the non-parametric Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups;the chi-square test was used for comparison of categorical data between groups.The Cox proportional-hazards regression model was used to assess the impact of CVAI and CRP alone or in combination on the risk of digestive malignancies.Results There were significant differences between the four groups in age,male/female ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,systolic blood pressure,diastolic blood pressure,fasting blood glucose,high-sensitivity C-reactive protein,waist circumference,body mass index,marital status,alcohol consumption,smoking,reported income,and physical exercise(all P<0.05).During a mean follow-up time of 14.08±2.76 years,2 043 new-onset cases of digestive malignancies were identified by the end of follow-up on December 31,2021.The Cox proportional-hazards regression model showed that after adjustment for CRP and other factors,compared with the low CVAI group,the high CVAI group had a hazard ratio(HR)of 1.34(95%confidence interval[CI]:1.23-1.47)for the risk of digestive malignancies.After adjustment for CVAI and other factors,compared with the CRP≤3 mg/L group,the CRP>3 mg/L group had an HR of 1.14(95%CI:1.02-1.28)for the risk of digestive malignancies.Compared with the CVAI(-)CRP(-)group(n=40 978),the CVAI(-)CRP(+)group(n=6 210),the CVAI(+)CRP(-)group(n=36 502),and the CVAI(+)CRP(+)group(n=10 687)had an HR of 1.05(95%CI:1.01-1.09,P<0.05),1.32(95%CI:1.20-1.45,P<0.05),and 1.48(95%CI:1.28-1.70,P<0.05),respectively,for the risk of digestive malignancies.As for digestive malignancies at specific locations,the CVAI(+)CRP(+)group had an increased risk of liver cancer,gastric cancer,pancreatic cancer,colorectal cancer,and small intestinal cancer with an HR of 1.35(95%CI:1.05-1.81,P<0.05),1.48(95%CI:1.09-2.00,P<0.05),1.60(95%CI:1.07-2.41,P<0.05),1.76(1.40-2.21,P<0.05),and 3.85(95%CI:1.43-10.33,P<0.05),respectively.Conclusion A high level of CVAI,a high level of CRP,and high levels of CVAI and CRP in combination can all increase the risk of digestive malignancies,among which the high levels of CVAI and CRP in combination may lead to a higher risk.

AIM To investigate the effects of Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction(GJHQHLRSD)on the pyroptosis,pathway of colonic epithelial cells in mouse models of ulcerative colitis(UC).METHODS Among the 63 C57BL/6J mice,13 were randomly selected and assigned to the model group,and the others were divided into the control group,the positive Sulfasalazine Enteric-Coated Tablets group(0.6 g/kg),and low,medium,and high dose GJHQHLRSD groups(3.9,7.8,15.6 g/kg),with 10 mice in each group.The UC mouse model was established using DSS,and the corresponding drugs were administered by gavage.The mice had their general condition observed;their disease activity index(DAI)score assessed;their colon length measured;their histopathological damage of the colon analyzed using HE staining;their colonic IL-1β,IL-8,and TNF-α levels measured by ELISA method;their colonic NLRP3,GSDMD,pro-IL-1β,pro-caspase-1,and IL-1βprotein expression detected by Western blot method;and their cell pyroptosis detected by TUNEL and GSDMD fluorescence double staining.RESULTS Compared with the control group,the model group exhibited significant decrease in body weight and a shortened colon length(P＜0.01);increases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);significant increase of colonic GSDMD and TUNEL positivity;indicating increased tissue damage and inflammatory response.Compared with the model group,the groups intervened with GJHQHLRSD showed a significant increase in body weight and colonic elongation(P＜0.05,P＜0.01);decreases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);a gradient decrease in positivity of GSDMD and TUNEL;indicating a significantly reduced colonic pathological damage.CONCLUSION GJHQHLRSD can improve the DSS-induced inflammatory reaction of colonic mucosa in UC mice,and its mechanism mainly involves the NLRP3/caspase-1,thereby the regulation of the cell pyroptosis process.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome