Pathology diagnosis is the "gold standard" for clinical disease diagnosis and treatment. Intelligent pathology image analysis has significant clinical value in improving diagnostic efficiency and ensuring consistency. This paper systematically reviews the core multiple instance learning paradigm for whole slide image analysis, and elaborates the pretraining system, core functional branches and latest advances of pathology foundation models. Taking clinical usability as the core evaluation dimension, it establishes a multi-dimensional evaluation framework, analyzes the clinical translation potential of different technical routes, and points out the core contradiction of "excellent laboratory performance but insufficient clinical usability" in current pathology foundation models. It further dissects the key clinical translation bottlenecks of pathology foundation models, outlines future application and development directions, and provides a reference for technological research and development as well as clinical translation in computational pathology.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

This article reports a first case of combined infection with severe fever with thrombocytopenia syndrome(SFTS)and scrub typhus in Dalian City.The patient was admitted to the hospital due to recurrent fever for 7 days and loss of consciousness for 1 day.Pathogen metagenomic sequencing(mNGS),SFTSV quantitative PCR,and enzyme-linked immunosorbent assay(ELISA)IgM tests were performed,showing positive results for Orientia tsutsugamushi and SFTSV nucleic acids.Based on clinical manifestations and epidemiological history,the patient was diagnosed with combined infections.

Objective To analyze Wu Zihui's medication rules for treating insomnia through data mining technology.Methods A total of 131 medical cases diagnosed with insomnia and admitted to the Outpatient Department of Wu Zihui at the International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine from June 2020 to March 2024 were sorted out.After standardizing the entered medical case data using the Gujin Medical Case Cloud Platform V2.3.9,statistical analysis,cluster analysis and complex network analysis of the prescription drugs were conducted respectively to summarize the experience of prescription drug use and the rules of formula composition.Results A total of 131 medical cases involved 143 traditional Chinese medicines.It was concluded that the properties were mainly cold and neutral,the flavors were mainly sweet and bitter,the meridians were mainly liver and heart meridians,and high-frequency drugs,Baishao Baizhu,Nyuzhenzi etc.Cluster analysis yielded 5 clustering prescriptions.Complex network analysis of traditional Chinese medicine syndrome types and drugs can result in two core traditional Chinese medicine prescriptions for insomnia syndrome.Conclusion In the treatment of insomnia,attention should be paid to the treatment of heart,liver,spleen and kidney.The treatment principle should be to relieve liver depression,clear heat and purge fire,nourish heart and calm the mind,and supplement spleen and kidney.

Objective To analyze Wu Zihui's medication rules for treating insomnia through data mining technology.Methods A total of 131 medical cases diagnosed with insomnia and admitted to the Outpatient Department of Wu Zihui at the International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine from June 2020 to March 2024 were sorted out.After standardizing the entered medical case data using the Gujin Medical Case Cloud Platform V2.3.9,statistical analysis,cluster analysis and complex network analysis of the prescription drugs were conducted respectively to summarize the experience of prescription drug use and the rules of formula composition.Results A total of 131 medical cases involved 143 traditional Chinese medicines.It was concluded that the properties were mainly cold and neutral,the flavors were mainly sweet and bitter,the meridians were mainly liver and heart meridians,and high-frequency drugs,Baishao Baizhu,Nyuzhenzi etc.Cluster analysis yielded 5 clustering prescriptions.Complex network analysis of traditional Chinese medicine syndrome types and drugs can result in two core traditional Chinese medicine prescriptions for insomnia syndrome.Conclusion In the treatment of insomnia,attention should be paid to the treatment of heart,liver,spleen and kidney.The treatment principle should be to relieve liver depression,clear heat and purge fire,nourish heart and calm the mind,and supplement spleen and kidney.

AIM To rapidly screen xanthine oxidase(XOD)inhibitors from Smilax glabra Roxb.by enzyme-immobilized magnetic microspheres and LC-MS/MS,and to confirm the anti-uric acid constituents from S.glabra Roxb.METHODS The immobilized xanthine oxidase was prepared by covalent coupling with carboxyl magnetic beads as a carrier.The xanthine oxidase inhibitors in S.glabra were screened by the specific adsorption of immobilized enzyme.LC-MS/MS and standard substances were used for analysis and comparison,and the inhibitory activity and inhibition type of the screened and identified components were investigated.RESULTS The successful synthesis of immobilized xanthine oxidase was characterized by scanning electron microscopy and infrared spectroscopy.The enzyme loading was 70.50 μg/mg and the relative activity was 79.44%.Thirteen active compounds were screened from the extract of S.glabra,and eleven compounds were identified.The enzyme activity test showed that the inhibitory activites of engeletin and isoengeletin were the strongest,which was close to the positive control allopurinol.The IC50 value and inhibition type were 32.25 μg/mL,mixed inhibition,35.12 μg/mL,competitive inhibition.CONCLUSION The method is simple,rapid,accurate and suitable for directly screened active ingredients which can inhibit XOD from complex extract of traditional Chinese medicines.

Cardiac contractility modulation(CCM),as a new implantable electronic therapy device for treating chronic heart failure with reduced ejection fraction(HFrEF),has rapidly become a hot topic in the cardiovascular field due to its ability to enhance ventricular myocardial contractility,improve patients'symptoms and signs,cardiac function indexes and even long-term prognosis.This article reviews the mechanism and clinical studies of CCM in treating HFrEF,and based on its mechanism and signal transduction algorithm,further analyzes and prospects its efficacy in patients with heart failure with preserved ejection fraction,cardiac resynchronization therapy non-response,and HFrEF with concomitant atrial fibrillation,aiming to promote CCM to meet the needs of more diverse clinical situations in heart failure patients.

Objective To observe the clinical efficacy of warming-needle moxibustion combined with cross acupoint selection method in the treatment of knee osteoarthritis(KOA).Methods Fifty patients with KOA were randomly divided into observation group and control group,25 patients in each group.The control group was treated with warming-needle moxibustion on local of the knee joint,and the observation group was treated with elbow cross acupoint selection on the basis of the treatment of the control group.The course of treatment covered five days,with an interval of one day between courses of treatment,and a total of two courses of treatment.After two courses of treatment,the changes in Visual Analogue Scale(VAS)scores and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores in the two groups before and after treatment were observed.Changes in step frequency,step speed,step length,stride,and gait period between the two groups of patients before and after treatment were compared.Results(1)During the research,there was one case in the observation group and four cases in the control group lost to follow-up.Finally,24 cases in the observation group and 21 cases in the control group were included in the efficacy statistics.(2)After treatment,the scores of VAS and WOMAC of patients in the two groups decreased significantly(P＜0.01),and the improvement in the observation group was significantly superior to that in the control group,and the differences were statistically significant(P＜0.05).(3)After treatment,the step frequency and step speed of patients in the two groups were significantly improved compared with those before treatment,and the difference was statistically significant(P＜0.05),and the parameters of step length and stride were slightly improved compared with those before treatment,but the difference was not statistically significant(P＞0.05).After treatment,the observation group was slightly superior to that in the control group in improving the patients'step frequency,step length,step speed and stride,but the difference was not statistically significant(P＞0.05).(4)After treatment,the gait period of patients in both groups were improved significantly(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,but the difference was not statistically significant(P＞0.05).Conclusion The efficacy of warming-needle moxibustion combined with cross acupoint selection method in the treatment of KOA is precise,with good analgesic effect,moreover,it can significantly improve the daily joint function of the patients,and improve the step frequency and step speed of patients with KOA and shorten the gait period,so as to improve the quality of life of patients,with remarkable therapeutic effect.

Objective:To investigate the birth weight (BW) of infants born to pregnant women living with human immunodeficiency virus (HIV) and its associated factors, and to provide more evidence for the prevention of mother-to-child transmission (PMTCT) in China.Methods:This study was a retrospective cohort study. Between January 2004 and December 2021, pregnant women living with HIV and their infants in Hubei Province were recruited and followed up, and clinical data were collected through hospital medical records and HIV/acquired immunodeficiency syndrome comprehensive response information management system. The multivariable linear regression was performed on the collected data to investigate associated influencing factors of BW.Results:In total, 531 pregnant women living with HIV (581 pregnancies) and 581 infants were enrolled. Of the 581 infants, 36 were HIV-positive, with a PMTCT rate of 6.2%. The mean BW of the infants was (3 075.0±470.2) gram. Protease inhibitor (PI) based-anti-retroviral therapy (ART) ( β=-0.1, 95% confidence interval ( CI)-188.2 to -37.1, P=0.004), ART in the first trimester( β=-0.1, 95% CI -201.9 to -65.5, P<0.001), infant HIV infection ( β=-0.1, 95% CI -310.4 to -68.2, P=0.002), hepatitis C virus infection ( β=0.1, 95% CI 71.2 to 410.4, P=0.005) and gestational age ( β=0.6, 95% CI 155.9 to 191.5, P<0.001) were associated with decreased BW. Conclusions:While improving the effectiveness of PMTCT for HIV, more attention should be paid to pregnant women who received ART in the first trimester and PI-based ART for preventing lower BW and improving maternal and infantile health.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.