This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.

Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.

Objective To explore the correlation between lung injury and human neutrophil lipocalin(HNL)in rats with sepsis.Methods 45 rats were randomly divided into a control group,a sham group,and a model group.The model group was to construct a rat sepsis lung injury model,the sham group was to free cecum laparotomy and then close abdomen without ligation and puncture,and the control group was with healthy rats.Serum interleukin(IL)-6,IL-1β,tumor necrosis factor-a(TNF-α),and HNL in each group of rats were detected with reagent kit.Oxygenation index was detected by blood gas analysis system.Lung wet/dry(W/D)ratio was calculated.Patho-logical morphology of lung tissue was observed by HE staining,and lung injury score was calculated.Results There were no significant differences in IL-6,IL-1β,TNF-α,HNL levels,oxygenation index,lung tissue wet/dry ratio,and lung injury score between the control group and the sham group at 12,24 and 36 hours(all P＞0.05).Compared with the sham group,IL-6,IL-1β,TNF-α,HNL levels,oxygenation index,lung tissue wet/dry ratio,and lung injury score in the model group increased at 12,24 and 36 hours,with significant differences(all P＜0.05).At 12,24 and 36 hours,lung tissue structure of rats was normal in the control group,with no edema ob-served;there were only a few inflammatory cells in the lung tissue of rats from the sham group;while in the model group,lung tissue structure of rats was severely injured,pulmonary alveoli collapsed,and inflammatory cells were severely infiltrated,but pathology improved with time.In rats with sepsis and lung injury,HNL was positively cor-related with IL-6,IL-1β,TNF-α,lung wet/dry ratio,and lung injury scores(all P＜0.05),while negatively corre-lated with oxygenation index(P＜0.05).Conclusion In rats with sepsis lung injury,HNL increases significantly,with severe inflammation and aggravation in lung tissue wet/dry ratio and lung injury,while oxygenation index de-creases.HNL level is positively correlated with IL-6,IL-1β,TNF-α levels,lung tissue wet/dry ratio and lung inju-ry,but negatively correlates with oxygenation index.

Objective:To prepare mesenchymal stem cells with antioxidant capacity (AO-MSC ) from human umbilical cords and evaluate its cell biological properties.Methods:In control group,mesenchymal stem cells (MSC) were isolated by digesting human umbilical cord Wharton's Jelly tissues with 0.2％ collagenase Ⅱ,and the released cells were collected and cultured in an animal serum-free culture medium.In AO-MSC group,incompletely collagenase Ⅱ-digested tissue debris were allowed to adhere to flusk flat bottoms and the AO-MSC was harvested by adherent culture. The conventional digestion and culture method was used as control.MSC colony forming ability was evaluated by fibroblast colony forming assay (CFU-F).MSC proliferative capacity was evaluated by CCK-8 assay.The MSC surface markers were detected by using flow cytometry and immunofluorescence staining.The adipogenic and osteogenic capacity of MSC was evaluated by multi-differentiation in vitro,and the mRNA expression of genes that control adipogenic and osteogenic differentiation was detected by real-time fluorescence quantitative PCR (RT-qPCR );Moreover,the mRNA expression of antioxidant substances such as SOD-1,GSH,GAT,and NQO1 in MSC was also evaluated by RT-qPCR.Results:The AO-MSC isolated by this strategy reached a confluence of 80％-90％ at around 18 days and grew in a swirling pattern.Flow cytometry and immunofluorescence staining assays showed that CD73,CD29,CD105,CD90 were highly expressed and CD31,CD45,HLA-DR were scarcely expressed in AO-MSC.AO-MSC exhibited stronger self-renewal and differentiation ability compared to MSC.However,the in vitro adipogenic-osteogenic capacity of MSC in the control group was stronger than that of AO-MSC.RT-qPCR assay showed that AO-MSC expressed higher mRNA levels of antioxidant substances compared to MSC.Conclusion:Human AO-MSC is successfully prepared from human umbilical cord without animal serum.

Objective To investigate the experience of intrauterine device(IUD)removal in patients with cervical cancer after radiotherapy.Methods A total of 23 patients with cervical cancer after radiotherapy underwent abdominal ultrasound guided hysteroscopic removal of IUD in our department from January 2020 to December 2022.For vaginal and/or cervical adhesions,blunt separation of adhesions was performed by using hysteroscope head or curved forceps under abdominal ultrasound guidance.If it was difficult to separate the adhesions for hysteroscope head entering the uterine cavity,a probe was inserted into the uterine cavity under ultrasound guidance,and the cervical canal was gradually expanded to 6-caliber dilation rod.Then the hysteroscope was inserted again into the uterine cavity.For obvious cervical atrophy that was tough in which cervical forceps could not be used to clamp the cervix,a 1-0 absorbable suture line was used to suture the anterior and/or posterior lips of the atrophied cervix at the top of the vagina,with an assistant firmly pulling and fixing the cervix.Results There were 4 cases of vaginal partial adhesions and cervical contracture,10 cases of cervical contracture,and remaining 9 cases having no vaginal adhesions and cervical contracture.Under hysteroscopy,there were 3 cases of cervical adhesions,2 cases of endometrial polyps,1 case of submucosal uterine fibroids,2 cases of uterine abscess,2 cases of incarcerated IUD,and remaining 13 cases having normal uterine cavity morphology.All the 23 cases of IUD were successfully removed by using abdominal ultrasound guided hysteroscopy(circular shaped in 12 cases,uterine shaped in 6 cases,V-shaped in 2 cases,Y-shaped in 1 case,T-shaped in 1 case,and umbrella shaped in 1 case).The surgical time was(19.2±10.9)min,and there were no complications such as false passage formation,uterine perforation,organ damage,massive vaginal bleeding,transurethral resection of the prostate syndrome,infection,embolism,or shock.The 23 cases were followed up for 2-24 months postoperatively,with a median of 12 months.One case continued concurrent radiotherapy and chemotherapy,3 cases continued post-loading radiotherapy,1 case continued chemotherapy,and 2 cases received targeted treatment(distant metastasis).The remaining 16 cases recovered well in regular reviews without complications such as abdominal pain,fever,or vaginal bleeding.Conclusions If the size and location of the cancer lesion do not affect the removal of IUD after radiotherapy for cervical cancer,it should be removed as soon as possible.The application of abdominal ultrasound guided hysteroscopy in IUD removal in patients with cervical cancer after radiotherapy is safe and feasible to a certain extent.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

BACKGROUND: Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia. METHODS: In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared. RESULTS: A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05). CONCLUSIONS The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.
Humans ; Retrospective Studies ; Pneumonia/diagnostic imaging* ; Analysis of Variance ; Tomography, X-Ray Computed ; Lymphoma/diagnostic imaging*