Breast cancer has become the malignant tumor with the highest incidence rate among women， seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia， and from pre-cancerous lesions to cancerous lesions， is a long-term progressive process. Therefore， early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer， which is mainly based on surgery and systemic treatment， whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer， surgery is also the mainstay of treatment. In recent years， traditional Chinese medicine （TCM） has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions， TCM compound prescriptions， single herbs or herb pairs， and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion， promote the apoptosis and autophagy of tumor cells， and regulate the cell cycle and the immune microenvironment， thus exerting anti-tumor effects. At the same time， they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However， the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， and Notch， which still need to be verified by a large number of clinical and experimental studies. Therefore， this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years， aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.

Objective To evaluate the clinical characteristics, diagnostic reasoning, and therapeutic strategies of prostatic paraganglioma (PPG) to provide an evidence-based foundation for early diagnosis and precision treatment of this rare malignancy. Methods The clinical data of a patient with PPG admitted to our hospital were retrospectively analyzed. Concurrently, a systematic search was conducted across domestic and international databases, including PubMed, CNKI, and Wanfang.Clinical manifestations, laboratory tests, pathological features, therapeutic modalities, and prognostic data of 24 cases reported between 1979 and 2025 were pooled with the institutional case for a comprehensive analysis (n=25). Results Epidemiological features: the age at onset ranged from 8 to 76 years, with a mean age of (44.6±15.2) years, predominantly affecting young and middle-aged adults (30-50 years).Notably, 20.0% (5/25) of the patients exhibited characteristic micturition-associated catecholamine release symptoms (e.g., post-micturition palpitations, transient hypertension).Laboratory findings: among the 19 patients who underwent catecholamine metabolite testing, 14 (73.7%) showed significant elevation in serum or urinary norepinephrine and methoxyadrenaline levels.Pathological and immunohistochemical features: the positivity rate for neuroendocrine markers (chromogranin A, synaptophysin, and neuron-specific enolase) was 100%, while the negativity rate for prostate-specific markers (prostate-specific antigen and prostate-specific acid phosphatase) was also 100%.Treatment and prognosis: surgical intervention was performed in 96.0% (24/25) of the patients, including radical prostatectomy (37.5%), precision tumor excision (25.0%), and transurethral resection (12.5%).Favorable outcomes without recurrence were observed in 89.5% (17/19) of the total cohort. Conclusion PPG is clinically exceedingly rare.The disease should be highly suspected in patients presenting with a prostatic mass, normal prostate-specific antigen level, and micturition-associated cardiovascular symptoms.Testing for catecholamine metabolites is the key screening tool.Robot-assisted surgery facilitates precise tumor excision while ensuring optimal functional preservation.Given the malignant potential and genetic correlations of PPG, lifelong follow-up is recommended.

Objective:To analyze the epidemiological characteristics and trend of acute hemorrhagic conjunctivitis (AHC) in China from 2015 to 2022, and to provide evidence for the adjustment of prevention and control strategies and measures for AHC.Methods:The case data of AHC reported by national notifiable disease information system from 2015 to 2022 were collected, and descriptive analysis method were used to analyze the population distribution characteristics, temporal epidemiological trends and spatial clusters of AHC in China.Results:From 2015 to 2022, the incidence of AHC in China ranged from 1.85/100 000 to 2.97/100 000, with a fluctuating downward trend. The average annual percent change (AAPC) was -4.91 (95% CI: -7.74 to -2.00, P<0.05), with an annual percent change (APC) of 2.73 (95% CI: -2.34 to 8.06, P=0.189) for 2015—2019 and an APC of -14.23 (95% CI: -21.78 to -5.94, P<0.05). The age-specific incidence rate was highest in children aged 0-4 years (fluctuating between 4.69 and 5.67/100 000 from 2015 to 2019; It decreased significantly during 2020—2022, fluctuating between 1.93 and 2.72 per 100 000).The proportion of cases in children at 0-4 years of age showed a fluctuating downward trend from 8.68% in 2015 to 3.76% in 2020, with an increase in 2021—2022 to 5.74%. After 2020, the proportion of the population aged 60 years and above has increased, reaching 33.59% in 2022. Cases were mainly farmers, with a fluctuating upward trend of around 50% per year, with the highest percentage of 60.96% in 2020. The peak seasonal incidence of AHC was obvious from May to September from 2015 to 2019, but it was not obvious in 2020—2022. The cases were mainly distributed in Guangxi, Hainan and other provinces in the southwestern part of China. The high incidence counties were concentrated in Leye County of Guangxi, Maojian District of Hubei, Fuchuan Yao Autonomous County of Guangxi, Funing County of Yunnan, and Pulan County of Tibet every year. Conclusions:The overall epidemic rate of AHC in China showed a fluctuating downward trend from 2015 to 2022, with a pronounced decline observed between 2020 and 2022, potentially linked to non-pharmaceutical interventions during the COVID-19 pandemic. Increased attention needs to be given to farmers and people above 60 years of age to reduce the risk of morbidity. Moreover, prevention and control efforts should be strengthened in high-risk areas of southwestern China, and comprehensive measures should be implemented in counties with high incidence, including enhanced health education campaigns and improved allocation of sanitary facilities, to reduce the risk of AHC infection. This study is the first to highlight the potential impact of public health policies on AHC epidemiology, thereby offering a scientific foundation for population- and region-specific precision prevention strategies, particularly guiding the refinement of control measures in high-burden areas.

Objective:To establish a rapid and accurate duplex real-time fluorescent reverse transcription-recombinase polymerase amplification/recombinase-aided amplification（RT-RPA/RAA）detection method for identification and differentiation of Nipah virus（NiV），Langya virus（LayV），Mojiang virus（MoJV），and Cedar virus（CedV）.Methods:First，specific primers and probes were designed targeting the conserved L gene regions of NiV and LayV，as well as the conserved N gene regions of MoJV and CedV，respectively. The four viruses were divided into two groups for duplex detection. Subsequently，the optimal primer and probe combinations were screened by comparing the amplification efficiency of different primer pair combinations（F1/R1，F1/R2，F2/R1，F2/R2）. The reaction temperature was optimized through temperature gradient settings from 37 ℃ to 42 ℃，and the amounts of primers and probes were optimized to establish the duplex real-time fluorescent RT-RPA/RAA detection system. Finally，the detection performance was evaluated through specificity，sensitivity，and stability tests，as well as clinical sample validation.Results:The selected primer pairs（NiV primer pair F2/R1，LayV primer pair F1/R1，MoJV primer pair F2/R2，and CedV primer pair F2/R2）all demonstrated optimal amplification efficiency when combined with their corresponding probes. The optimal annealing temperature was 39 ℃，and the minimum detection limit was 101-102 copies/μl. The method could effectively distinguish target viruses from other non-target viruses，and repeated experiments showed good stability（ R2> 0.90）. Additionally，detection results for Malaysian NiV strains and various clinical samples were consistent with the Taqman multiplex qRT-PCR method. Conclusion:The duplex real-time fluorescent RT-RPA/RAA detection method successfully established in this study can rapidly and accurately identify and differentiate four important henipavirus-like viruses：NiV，LayV，MoJV，and CedV. It features simple operation，rapid reaction，high specificity，and good stability，providing an effective molecular detection tool for rapid field diagnosis，surveillance，and control of these zoonotic viruses.

Objective:To deeply analyze the epidemiological characteristics and changing trends of intestinal infectious diseases in China, and provide scientific evidence for the prevention and control of intestinal infectious diseases.Methods:The incidence data of notifiable intestinal infectious diseases in China from 2013 to 2022 were collected from China Disease Prevention and Control Information System. Descriptive statistical method was used to analyze the distributions of intestinal infectious diseases in China, and the annual change rate and seasonal index were calculated.Results:During 2013-2022, intestinal infectious diseases were reported nationwide, with the cases accounting for 43.50% of all notifiable infectious disease cases. The average reported incidence rate was 224.50/100 000, showing a decreasing trend year by year (average annual percent change=-6.45%, t=-2.76, P=0.025). The top 5 intestinal infectious diseases were hand foot and mouth disease (HFMD) (130.40/100 000), other infectious diarrhea (80.18/100 000), dysentery (7.45/100 000), acute hemorrhagic conjunctivitis (2.49/100 000) and viral hepatitis E (1.92/100 000). The incidences of dysentery, HFMD, typhoid fever/paratyphoid fever, viral hepatitis A and acute hemorrhagic conjunctivitis all showed decreasing trends year by year (all P<0.05), while the incidences of hepatitis E and other infectious diarrhea showed no significant changes with year (both P>0.05). The incidence of intestinal infectious diseases was high during May to October, with the peak in June. The incidence rate of intestinal infectious diseases was significantly higher in men than in women (all P<0.05). The HFMD, other infectious diarrhea and dysentery cases were mainly children aged 0-5 years, while the cholera, hepatitis A, hepatitis E, typhoid fever/paratyphoid fever and acute hemorrhagic conjunctivitis cases were mainly farmers aged ≥20 years. The annual reported incidence rate of intestinal infectious diseases was higher in southern provinces (283.66/100 000) than in northern provinces (142.63/100 000), and the annual reported incidence rate of intestinal infectious diseases was higher in coastal provinces (279.52/100 000) than in inland provinces (181.78/100 000), the differences were all significant (both P<0.001). Conclusions:During 2013-2022, the incidence of intestinal infectious diseases decreased significantly in China, with HFMD and other infectious diarrhea as the main diseases. Strengthened surveillance for intestinal infectious diseases should be carried out in key groups, such as children living scatteredly and farmers, and targeted prevention and control measures should be taken according to the epidemiological characteristics of different diseases to effectively reduce the incidence of intestinal infectious diseases.

[Objective]To investigate a simple method for the rapid detection and precise analysis of trace triptolide(TP)in vitro.[Methods]Initially,4-carboxy-4'-methyl-2,2'-bipyridine(Me-bpy-COOH)and cis-bis(2,2'-bipyridine)dichlororuthenium(Ⅱ)(cis-Ru(bpy)2CL2)were used as raw materials to synthesize tripyridine ruthenium monocarboxylic acid fluorescent reagent,namely bis(2,2'-bipyridyl)(4-methyl-4'-carboxy-2,2'-bipyridyl)ruthenium(Ⅱ)bishexafluorophosphate[Ru(bpy)2(bpy-COOH)2PF6].Subsequently,the pre-column derivatization reaction conditions of Ru(bpy)2(bpy-COOH)2PF6 with TP was optimized through orthogonal test and a methodological evaluation of the high performance liquid chromatography-fluorescence detection(HPLC-FLD)of triptolide-terpyridine ruthenium derivative(TTRD)was conducted.Taking commercially available Kunxian Capsules as object,the newly established evaluation method was adopted for detection.[Results]A fluorescent derivative of TP,TTRD was obtained and was characterized by proton nuclear magnetic resonance(1H-NMR)and ultra high performance liquid chromatography-mass spectrometry(UPLC-MS).The optimized pre-column derivatization reaction conditions were a 4:1 molar ratio of Ru(bpy)2(bpy-COOH)2PF6 to TP,a reaction time of 2 hours and a reaction temperature of 45℃.This study presented a HPLC-FLD method for the pre-column derivatization of TP.The method demonstrated a good linear relationship within the range of 50 to 1 200 μg·L-1.The TP content in Kunxian Capsules was measured by using this method,yielding a result of 78.78 μg·g-1,which fell within the prescribed range of national drug standards.[Conclusion]The pre-column-derived HPLC-FLD method for TP exhibited good sensitivity,accuracy and reliability,expanding the HPLC detection range for TP.

Objective To systematically evaluate influence factors hospitalization infections in multiple myeloma(MM)patients after chemotherapy.Methods Computer searches were conducted on relevant literature in CNKI,China Biology Medicine disc,VIP,Wanfang Data Knowledge Service Platform,PubMed,Web of Science,Embase,Cochrane Library and CINAHL from the database inception until December 16,2024.Two researchers independently screened and assessed the quality of the literature,obtained the necessary information,and a Meta-analysis of risk factors was conducted by using RevMan 5.4 software.Results 19 articles were included in total.Meta-analysis results showed that high body mass index,length of stay,smoking history,Eastern Cooperative Oncology Group(ECOG)score,granulocyte deficiency,neutropenia,Durie-Salmon stage,international staging system(ISS)stage and combined with diabetes,renal insufficiency,anemia,hypoalbuminemia were the risk factors for hospitalization infections in patients with MM after chemotherapy(P＜0.05).Conclusion This study provides a reference for intervening in the risk factors of hospitalization infections in MM patients after chemotherapy.Medical staff should prevent infections early based on relevant factors,identify high-risk populations,and maximize the protection of patient health outcomes and good prognosis.

Objective To explore the role and underlying mechanism of the transcriptional coactivator with PDZ-binding motif(TAZ)and a histone variant of acute histone H2A(H2A.Z)in the repair of hypoxia-induced lung injury.Methods A mouse model of hypoxic lung injury was established by being placed in a hypoxia chamber(simulating an altitude of 5 800 m)for 4 d.HE staining was used to observe the severity of lung injury.A hypoxia model of murine alveolar epithelial cells(murine lung epithelial-12,MLE12)was constructed by treating the cells in a hypoxia workstation(1%O2 concentration)for 24 h.Western blotting was employed to detect TAZ expression.The proliferation of alveolar epithelial cells(AECs)was evaluated by CCK-8 assay.Co-immunoprecipitation(Co-IP)assay was utilized to verify the interaction between TAZ and H2A.Z.CUT&Tag sequencing was performed to determine the effect of TAZ on the chromatin deposition of H2A.Z.Results Hypoxia significantly induced alveolar atrophy and inflammatory infiltration in mouse lung tissues(P＜0.01).Hypoxia significantly up-regulated the protein level of TAZ in MLE12 cells(P＜0.05).CCK-8 assay showed that knockdown of TAZ significantly reduced the proliferative capacity of AECs(P＜0.01).Co-IP assay confirmed the physical interaction between TAZ and H2A.Z.CUT&Tag sequencing revealed that hypoxia promoted the deposition of H2A.Z on chromatin(31 817 peaks under normoxia,44 078 peaks under hypoxia),which was partially reversed by TAZ knockdown(37 840 peaks).Conclusion Hypoxia significantly up-regulates the expression of TAZ,which combines with H2A.Z and promotes the deposition of H2A.Z on chromatin,thus enhancing the proliferation of AECs in response to hypoxic injury.

Objective To explore the effects of hypoxia on spermatid differentiation and stability of sperm flagellar microtubule,and investigate the underlying molecular mechanisms in order to clarify the potential adverse effects of hypoxia on male reproductive function.Methods Forty-eight 8-week-old healthy male SD rats(weighing 300～399 g)were subjected in this study.The experiments included ① an oxygen concentration gradient experiment(n=6):21％oxygen was regarded as normoxia(control),and 13.5％,11.8％,and 10.4％ oxygen were used to simulate hypoxic environments at altitudes of 3 500,4 500 and 5 500 m,respectively,for a continuous exposure of 2 months;② a time gradient experiment(n=6):the rats were exposed to 10.4％ oxygen for 0,0.5,1,and 2 months,respectively.Flow cytometry was employed to isolate round spermatids,and the following methods were employed to measure relevant indicators:① RNA sequencing to analyze gene expression profile changes related to impaired spermatogenesis and abnormal flagellar structure under hypoxic stress;②Western blotting to detect the expression levels of key proteins CEP290,RING 1A,and H2AK119ub;③ fluorescence recovery after photobleaching(FRAP)to monitor microtubule assembly dynamics and assess the immediate impact of hypoxia on microtubule stability.Results In the oxygen concentration gradient experiment,after 2 months of exposure to 10.4％ oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids in rat seminiferous tubules were significantly increased(P＜0.05),reaching 1.33±0.04,1.06±0.01 and 1.60±0.02 times higher,respectively than that of the 21％ normoxia group.Conversely,the proportions of primary spermatocytes and elongated spermatids were obviously decreased(P＜0.05),taking 0.89±0.01 and 0.88±0.000 2 times respectively when compared with that of the 21％ normoxia group,in a oxygen concentration-depended manner.In the time gradient experiment,after 0.5 months of exposure to 10.4％oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids began to increase(P＜0.05),reaching 1.11±0.03,1.04±0.01 and 1.29±0.003 times higher,respectively than that of the 0-month control group.The proportions of primary spermatocytes and elongated spermatids started to significantly decrease(P＜0.05)after 1 month of exposure,only 0.94±0.03 and 0.95±0.008 times,respectively than that of the 0-month control group.After 2 months of exposure to 10.4％ oxygen,the rate of sperm tail abnormalities in the epididymis of rats was significantly increased(P＜0.05),rising from(12.1±1.7)％ in the 21％ normoxia group to(30.8±3.7)％.In G2 spermatocytes exposed to 1％ hypoxia for 24 h,FRAP revealed a decrease in microtubule assembly rate and enhanced microtubule dynamic instability,with the maximum fluorescence recovery value decreasing from 0.37±0.02 in the normoxia group to 0.29±0.01.The results of RNA sequencing showed that under hypoxic condition,the transcription level of the key cilium basal body molecule CEP290 was increased,with an upregulation of 1.81±0.11 times than that of the 21％ normoxia group.In contrast,the expression levels of PRC1 complex members RING 1A,RING 1B,CBX2,PHC1,and PCGF1 were decreased,to 0.74±0.02,0.73±0.01,0.78±0.02,0.71±0.01 and 0.86±0.03 times of that of the 21％ normoxia group,respectively.Western blotting indicated that the protein level of CEP290 was up-regulated in the hypoxia group,while that of RING 1A was down-regulated.ChIP-qPCR experiments showed that the binding of RING 1A and its product H2AK119ub to the CEP290 promoter were significantly decreased(P＜0.000 1),with binding strengths of 0.38±0.02 and 0.52±0.06 times of that of the 21％ normoxia group,respectively.In siRING 1A-treated G2 cells,the binding of H2AK119ub to the CEP290 promoter was significantly decreased(P＜0.000 1),with a binding strength of 0.74±0.06 times of that of the control group,while CEP290 mRNA level was significantly increased(P＜0.000 1),with an up-regulation of 3.35±0.37 times.Conclusion Hypoxic environment impair sperm flagellar microtubule stability via the RING 1A-H2AK119ub-CEP290 signaling axis,which affects spermatid differentiation and leads to spermatogenic dysfunction.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.