Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Drug development encompasses multiple processes,wherein protein subcellular localization is essential.It promotes target identification,treatment development,and the design of drug delivery systems.In this research,a deep learning framework called LocPro is presented for predicting protein subcellular localization.Specifically,LocPro is unique in(a)combining protein representations from the pre-trained large language model(LLM)ESM2 and the expert-driven tool PROFEAT,(b)implementing a hybrid deep neural network architecture that integrates convolutional neural network(CNN),fully connected(FC)layer,and bidirectional long short-term memory(BiLSTM)blocks,and(c)developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels.Additionally,a dataset was curated and divided using a homology-based strategy for training and validation.Compar-ative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction.The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization.All in all,LocPro serves as a valuable complement to existing protein localization prediction tools.The web server is freely accessible at https://idrblab.org/LocPro/.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

Objective To investigate the effects and potential mechanisms of Marsdeniae Tenacissimae Caulis(Tongguanteng)injection and extract in human osteosarcoma cells proliferation,migration,invasion,and apoptosis.Methods MNNG/HOS,Saos-2 osteosarcoma cells,and normal bone marrow mesenchymal stem cells(BMSC)were cultured in vitro.Cells were incubated with different concentrations of Tongguanteng injection and Tongguanteng extract(40,60,80 mg/mL).Cell proliferation was evaluated by CCK-8 assay and plate colony formation assay.Cell migration and invasion were evaluated by scratch assay and Transwell assay.Cell apoptosis was evaluated by Hoechst33342 staining and Annexin-V/PI double staining assay.Bax,Bcl-2 and Caspase-3 mRNA expression were detected using RT-qPCR.The protein expressions of JAK1,p-JAK1,STAT3,p-STAT3 and MMP9 were detected by Western blot.Results Compared with the control group,both Tongguanteng injection and extract significantly decreased the survival rate of MNNG/HOS and Saos-2 cells,inhibited cell clone formation,migration,and invasion,induced cell apoptosis(P<0.05,P<0.01),promoted Bax mRNA and protein expression,inhibited Bcl-2 mRNA and protein expression,and up-regulated Caspase-3 mRNA and Cleaved Caspase-3 protein expression.Tongguanteng injection could significantly down-regulate the expressions of p-JAK1,p-STAT3 and MMP9 protein expression in Saos-2 cells(P<0.05,P<0.01).Conclusion Both Tongguanteng injection and Tongguanteng extract can significantly inhibit proliferation,migration and invasion of human osteosarcoma MNNG/HOS and Saos-2 cells,and induce apoptosis,with no significant difference in anti-tumor effect.The mechanism may be related to the inhibition of the activation of JAK1/STAT3 signaling pathway.

Objective:To construct and validate a risk-scoring model for predicting delayed onset of lactogenesis stage Ⅱ (DOL Ⅱ) in mothers separated from their premature infants.Methods:This was a retrospective study. (1) Modeling group: This group enrolled 310 mothers who were separated from their premature infants after delivery at Wuxi Maternal and Child Health Hospital from December 2021 to November 2022. They were further divided into the DOL Ⅱ group (144 cases) and the non-DOL Ⅱgroup (166 cases) according to whether they had DOL Ⅱ or not. Based on the results of multivariate logistic regression analysis, each risk factor was assigned a score, and a risk prediction scoring model was established. (2) Validation group: This group included 130 mothers of premature infants who experienced mother-infant separation after delivery at Wuxi Maternal and Child Health Hospital from December 2022 to March 2023. The area under the receiver operating characteristic (ROC) curve was used to evaluate the discrimination, and the Hosmer-Lemeshow test was used to assess the goodness of fit. The Chi-square test (or Fisher's exact probability test) or Wilcoxon rank sum test were used for inter-group data comparison. Results:This risk prediction scoring model included 10 risk factors [maternal age≥35 years old, hypertensive disorders of pregnancy, anemia, gestational diabetes mellitus, preterm rupture of membrane, start breastfeeding >6 hours, postpartum admission of maternal intensive care unit, cesarean section, score of Edinburgh Postpartum Depression Scale >9.5, postpartum neutrophil-to-lymphocyte ratio ≥4.369, Fatigue Scale-14 ≥7.5, body mass index in the first trimester ≥23.719 kg/m 2, postpartum BMI≥27.661 kg/m 2,and increase of BMI during pregnancy ≥5.393 kg/m 2], with an area under the ROC curve of 0.838 (95% CI: 0.795-0.882, P<0.001), a maximum Yoden index of 0.526, a specificity of 0.825, a sensitivity of 0.701, and an optimal threshold of 4.5. After rounding the score off to the nearest whole number, those with a score≥5 were defined as at high risk of DOL Ⅱ, while those with a score<5 were at low risk. Hosmer-Lemeshow test showed χ2=3.43 and P=0.634. The positive predictive value, the negative predictive value, and the accuracy were 77.7%, 76.1%, and 76.8%, respectively. In the modeling group, 130 out of the 310 cases (41.9%) were predicted to be at high risk by the model with 101 (32.6%) experiencing DOL Ⅱ, while 180 cases (58.1%) were predicted to be at low risk with 43 (13.9%) experiencing DOL Ⅱ. Among the 130 cases in the validation group, 59 (45.4%) were predicted to be at high risk with 39 (30.0%) experiencing DOL Ⅱ, while 71 (54.6%) were predicted to be at low risk with 19 (14.6%) experiencing DOL Ⅱ. The model validation results showed that the area under the ROC curve was 0.774 (95% CI: 0.693-0.855, P<0.001) and the Hosmer-Lemeshow test showed χ2=3.09 and P=0.687, with the positive predictive value of 66.1%, the negative predictive value of 73.2%, and the accuracy of 70.0%. Conclusions:This study preliminarily establishes a risk scoring model for predicting DOL Ⅱ in mothers separated from their premature infants which is of certain predictive value and can provide a reference for developing predictive lactation support measures.

Objective:To investigate the risk factors of the occurrence of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis and the effect of proton pump inhibitor (PPI) on OHE.Methods:This study was led by the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) and Shanghai East Hospital of Tongji University School of Medicine, and a total of 13 hospitals participated. From July 31, 2020 to December 10, 2021, a total of 184 liver cirrhosis patients without prior OHE and with ≥2-year follow-up from the above 2 leading hospitals, and other hospitals such as Guangzhou Eighth People′s Hospital of Guangzhou Medical University and Affiliated Hospital of Zunyi Medical University were enrolled. According to whether OHE occurred during the 2-year follow-up period, the 184 patients were divided into OHE group (22 cases) and non-OHE group (162 cases). The clinical data of all the patients were collected, including the laboratory parameters such as international normalized ratio (INR), the usage of PPI, the occurrence of gastrointestinal bleeding, infection, liver cancer and other complications, and survival status. Multivariate logistic regression model was used to analyze the independent risk factors for OHE in patients with liver cirrhosis. Kaplan-Meier survival curve was performed to analyze the effect of PPI on the survival rate of patients with liver cirrhosis. Chi-square test and Cochran-Mantel-Haenszel test were used for statistical analysis.Results:The result of multivariate logistic regression analysis showed that INR ( OR=11.331, 95% confidence interval (95% CI) 2.415 to 53.156, P =0.002) and PPI ( OR=6.794, 95% CI 2.359 to 19.567, P<0.001) were independent risk factors for OHE in patients with liver cirrhosis. The rate of PPI usage of the OHE group was higher than that of the non-OHE group (72.7%, 16/22 vs. 30.9%, 50/162), and the difference was statistically significant ( χ2=14.76, P<0.001). After the patients with gastrointestinal bleeding, infection and liver diseases-related deaths were excluded respectively, the rates of PPI usage of the OHE group were still higher than that of the non-OHE group (8/12 vs. 21.3%, 27/127; 11/16 vs. 25.0%, 35/140; 12/15 vs. 29.0%, 45/155), and the differences were all statistically significant ( χ2=9.71, 11.20 and 15.94; all P<0.01). Kaplan-Meier survival curve analysis showed that the 2-year cumulative survival rate of liver cirrhosis patients with PPI usage was lower than that of the patients without PPI usage (86.4%, 57/66 vs. 95.8%, 113/118), and the difference was statistically significant ( χ2=5.37, P =0.020). Conclusion:PPI is an independent risk factor for OHE in patients with liver cirrhosis, and may increase the risk of liver disease-related death.

Objective:To investigate the risk factors of the occurrence of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis and the effect of proton pump inhibitor (PPI) on OHE.Methods:This study was led by the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) and Shanghai East Hospital of Tongji University School of Medicine, and a total of 13 hospitals participated. From July 31, 2020 to December 10, 2021, a total of 184 liver cirrhosis patients without prior OHE and with ≥2-year follow-up from the above 2 leading hospitals, and other hospitals such as Guangzhou Eighth People′s Hospital of Guangzhou Medical University and Affiliated Hospital of Zunyi Medical University were enrolled. According to whether OHE occurred during the 2-year follow-up period, the 184 patients were divided into OHE group (22 cases) and non-OHE group (162 cases). The clinical data of all the patients were collected, including the laboratory parameters such as international normalized ratio (INR), the usage of PPI, the occurrence of gastrointestinal bleeding, infection, liver cancer and other complications, and survival status. Multivariate logistic regression model was used to analyze the independent risk factors for OHE in patients with liver cirrhosis. Kaplan-Meier survival curve was performed to analyze the effect of PPI on the survival rate of patients with liver cirrhosis. Chi-square test and Cochran-Mantel-Haenszel test were used for statistical analysis.Results:The result of multivariate logistic regression analysis showed that INR ( OR=11.331, 95% confidence interval (95% CI) 2.415 to 53.156, P =0.002) and PPI ( OR=6.794, 95% CI 2.359 to 19.567, P<0.001) were independent risk factors for OHE in patients with liver cirrhosis. The rate of PPI usage of the OHE group was higher than that of the non-OHE group (72.7%, 16/22 vs. 30.9%, 50/162), and the difference was statistically significant ( χ2=14.76, P<0.001). After the patients with gastrointestinal bleeding, infection and liver diseases-related deaths were excluded respectively, the rates of PPI usage of the OHE group were still higher than that of the non-OHE group (8/12 vs. 21.3%, 27/127; 11/16 vs. 25.0%, 35/140; 12/15 vs. 29.0%, 45/155), and the differences were all statistically significant ( χ2=9.71, 11.20 and 15.94; all P<0.01). Kaplan-Meier survival curve analysis showed that the 2-year cumulative survival rate of liver cirrhosis patients with PPI usage was lower than that of the patients without PPI usage (86.4%, 57/66 vs. 95.8%, 113/118), and the difference was statistically significant ( χ2=5.37, P =0.020). Conclusion:PPI is an independent risk factor for OHE in patients with liver cirrhosis, and may increase the risk of liver disease-related death.