Objective: To investigate the trend in disease burden of interstitial lung disease (ILD) in China from 1990 to 2021, so as to provide a reference for formulating prevention and control strategies for chronic respiratory diseases. Methods: Based on the Global Burden of Disease 2021 database, data on the number of incident cases, incidence, standardized incidence, number of deaths, mortality, standardized mortality, number of disability-adjusted life years (DALY), DALY rate, and standardized DALY rate of ILD in China were collected. The incidence, mortality, and DALY rate were used to analyze the disease burden of ILD. The estimated annual percentage change (EAPC) was employed to assess the trend in standardized incidence, standardized mortality, and standardized DALY rate of ILD from 1990 to 2021. Rate decomposition analysis was applied to identify the main contributing factors affecting the trend in disease burden. Results: In 2021, China reported 48 514 cases, 7 674 deaths, and 222 288 person-years of DALY due to ILD, representing increases of 155.43%, 159.70%, and 97.34%, respectively, compared with 1990. From 1990 to 2021, the standardized incidence and standardized mortality of ILD in China showed upward trends (EAPC=1.106% and 0.239%, both P<0.05), while the standardized DALY rate showed a downward trend (EAPC=-0.230%, P<0.05). From 1990 to 2021, the standardized incidence and standardized mortality among males showed upward trends (EAPC=1.199% and 0.520%, both P<0.05), while the trend in the standardized DALY rate was not statistically significant (P>0.05). Among females, the standardized incidence of ILD showed an upward trend (EAPC=0.966%, P<0.05), while the standardized mortality and standardized DALY rate showed downward trends (EAPC=-0.306% and -0.760%, both P<0.05). In 2021, the incidence, mortality, and DALY rate of ILD in China increased with age, peaking in the group aged ≥95 years at 14.84/105, 13.90/105, and 124.71/105, respectively. Across all age groups aged ≥55 years, the incidence, mortality, and DALY rate of ILD were consistently higher in males than in females. The increase in the number of incident cases, deaths, and DALY due to ILD in China from 1990 to 2021 was primarily influenced by population aging, with contribution rates of 42.65%, 68.25%, and 69.79%, respectively. Conclusions From 1990 to 2021, the incidence and mortality risk of ILD in China showed upward trends, while the disability risk demonstrated a downward trend. Males bore a heavier disease burden of ILD, and aging was identified as the primary factor contributing to the increased burden of ILD in China.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

OBJECTIVE To explore the specific application and evaluation effect of objective structured clinical examination(OSCE)-guided scenario-based practical teaching mode in training clinical pharmacists. METHODS Fifty-six trainees who participated in the clinical pharmacist training program in the Second Xiangya Hospital of Central South University from October 2020 to September 2022 were selected as the research objects. OSCE-guided teaching was conducted, and the application effect of OSCE-guided teaching mode in clinical pharmacist training was explored and analyzed by using theoretical examination results and OSCE assessment results as evaluation indicators. RESULTS Through comparative analysis, it was found that the OSCE-guided teaching mode not only enabled students to better grasp the theoretical knowledge points required by the training outline, but also improved their clinical thinking ability, problem-solving ability, and communication and coordination skills to varying degrees. CONCLUSION For clinical pharmacist trainees, the OSCE teaching mode is conducive to the comprehensive improvement of clinical pharmacist skills and is suitable for cultivating clinical pharmacists who are capable of independently carrying out clinical pharmacy services in the new situation.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein re-sponse(UPR)in host cells,resulting in perturbation of endoplasmic reticulum homeostasis.To e-lucidate the action mechanism of isochlorogenic acid A(IAA)in regulating peste des petits rumi-nant virus(PPRV)-induced ERS and UPR,MTT assay,indirect immunofluorescence assay and Western blot were used to evaluate the anti-PPRV activity of IAA,and the effects of IAA on PPRV-induced ERS and PERK signaling pathway were studied by Western blot and quantitative real-time PCR.The results showed that the PPRV replication and virus-induced cytopathic in LDG-2 cells were significantly inhibited,and the survival rate of virus-infected cells was significantly in-creased due to IAA treatment.Compared with the virus control group,the expression levels of GRP78 and p-eIF2α,the ratios of p-PERK/PERK and p-eIF2α/eIF2α in IAA treated PPRV-infec-ted cells were significantly decreased.The expression level of GADD153 significantly decreased at 24,36 h,and significantly increased at 48,60 h.Furthermore,treatment with ERS inhibitor 4-PBA could significantly suppress the expression levels of GRP78,PPRV-N protein and GADD153 in PPRV-infected cells,and the ratios of p-eIF2α/eIF2α and p-PERK/PERK in PPRV-infected cells were also significantly decreased caused by treatment with IAA or 4-PBA and IAA combination.These findings implicated that the PPRV-induced ERS could be alleviated by inhibiting activation of the PERK-eIF2α-GADD1 53 signaling pathway,which led to restriction of PPRV replication in host cells.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein reac-tion(UPR)in host cells.This study aims to further explore the effects of ERS induced by pest des petits ruminants virus(PPRV)infection on UPR signaling pathway,virus replication and apopto-sis of host cells.MTT assay,indirect immunofluorescence assay(IFA)and Western blot were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and real-time flu-orescence quantitative PCR(qRT-PCR)were used to observe the effects of PPRV infection on the expression levels of GRP78,PERK and its downstream signal molecules,apoptosis-related proteins Bcl-2 and Bax.The result indicated that the cell survival rate was significantly declined with evident cytopathic effect at 36 h post-infection,and the expression level of PPRV-N protein tended to be elevated,and was significantly higher than that of cell control at 30 h post-infection.Meanwhile,the expression levels of GRP78,p-eIF2α and GADD153,the ratio of p-PERK/PERK and p-eIF2α/eIF2α were significantly increased.Moreover,the expression levels of PPRV-N protein,GRP78,p-eIF2α and GADD1 53,the ratio of p-eIF2α/eIF2α and p-PERK/PERK were significantly decreased in PPRV-infected cells due to 4-PBA treatment.The expression level of apoptosis-related Bcl-2 was down-regulated,Bax was up-regulated,and the ratio of Bcl-2/Bax was significantly decreased.Therefore,the activation of PERK/eIF2α/GADD153 signaling pathway could be induced by PPRV infection resulting in alleviating of virus-induced ERS,which is beneficial to viral replication.Bloc-king PPRV-induced ERS could inhibit the activation of PERK signaling pathway and virus replica-tion.PPRV infection and prolonged ERS can induce apoptosis of LDG-2 cells.

MTT assay,indirect immunofluorescence assay(IFA)and real-time fluorescence quanti-tative PCR(qRT-PCR)were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and qRT-PCR were used to evaluate the effects of PPRV infection on the expres-sion levels of TLR2,MyD88,NF-κB signaling pathway-related factors and their downstream in-flammatory factors.The results indicated that the significantly decreased cell survival rate and ob-vious cytopathic effect were observed at 36 h post PPRV infection,and the mRNA expression level of PPRV-N gene was significantly up-regulated.At the same time,the expression levels of TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors TNFα,IL-1β,IL-4 and IL-10 were significantly increased.Mo-reover,the expression levels of PPRV-N mRNA,TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors IL-1β and IL-4 in PPRV-infected cells were significantly decreased in the presence of the inhibitor C29 of TLR2.These findings implied that the TLR2/MyD88/NF-κBα signaling pathway can be activated by PPRV infection,which is beneficial to the replication and spread of the virus.Blocking down the activation of TLR2 can inhibit MyD88/NF-κB signaling pathway and viral replication in PPRV-infected cells.

Objective:To explore the efficacy of the combination of radiofrequency ablation(RFA) and endoscopic metal stent in the treatment of patients with unresectable cholangiocarcinoma.Methods:From January 3, 2012 to June 30, 2019, at the Department of Endoscopic of the Third Affiliated Hospital of Naval Medical University, the clinical data of 44 patients with unresectable cholangiocarcinoma who were treated by the combination of RFA and endoscopic metal stent were retrospectively collected, which included age, gender, location of cholangiocarcinoma(hilar cholangiocarcinoma and distal cholangiocarcinoma), etc. Postoperative evaluation was conducted based on the follow-up, including clinical success rate, postoperative complication rate, time of stent patency and overall survival time (OS). The Kaplan-Meier method and log-rank test were used to analyze the difference of OS between patients with hilar cholangiocarcinoma and distal cholangiocarcinoma. Mann-Whitney U test was used for statistical analysis. Results:The age of the 44 patients with cholangiocarcinoma was (70.3±11.6) years old, with 20 males (45.5%). There were 22 patients (50.0%) with hilar cholangiocarcinoma and 22 patients (50.0%) with distal cholangiocarcinoma. The clinical success rate of 44 patients was 93.2%(41/44). A total of 5 patients(11.4%) had postoperative complications, which were all improved by appropriate treatment. The median time of follow-up of the 44 patient was 9.2 months(ranged from 3.1 to 57.6 months), the median time of stent patency was 7.0 months (ranged from 5.8 to 8.2 months). Thirty-two patients (72.7%) died during the follow-up, and the median OS was 10.9 months(ranged from 9.0 to 12.8 months). The median OS of patients with hilar cholangiocarcinoma was 7.8 months(ranged from 4.6 to 11.0 months) and that of patients with distal cholangiocarcinoma was 12.5 months(ranged from 5.7 to 19.4 months), and there was no statistically significant difference( P>0.05). Conclusion:RFA combined with endoscopic metal stent is safe and effective in the treatment of patients with unresectable cholangiocarcinoma.

Objective:To evaluate the efficacy of endoscopic stenting drainage for patients with malignant hilar biliary obstruction caused by unresectable hepatocellular carcinoma.Methods:Data of 106 patients with malignant hilar obstruction caused by unresectable hepatocellular carcinoma who received endoscopic stenting drainage in the Third Affiliated Hospital of Naval Medical University from January 2012 to January 2019 were retrospectively analyzed. According to the different stent types, they were divided into the metal stent group (30 cases) and the plastic stent group (76 cases). The observation indexes included clinical success rate, complication incidence, stent patency and overall survival time. The independent predictors for stent patency and overall survival of patients were analyzed by multivariate Cox regression model.Results:The overall clinical success rate was 67.9% (72/106) and the incidence of postoperative cholangitis was 29.2% (31/106). The clinical success rates were 93.3% (28/30) and 57.9% (44/76) ( χ2=12.40, P<0.001), and the incidences of postoperative cholangitis were 13.3% (4/30) and 35.5% (27/76) ( χ2=5.12, P=0.024) in the metal stent group and the plastic stent group, respectively. The median stent patency was 5.2 (95% CI:3.7-6.0) months, and the overall survival time was 3.0 (95% CI:2.5-3.7) months. Multivariate Cox regression analysis showed that hepatic drainage volume <30% was an independent predictor for stent patency ( HR=2.12, 95% CI:1.01-4.46, P=0.048). Bismuth type Ⅳ ( HR=2.06, 95% CI:1.12-3.77, P=0.020), Child-Pugh class C ( HR=4.09, 95% CI: 2.00-8.39, P<0.001) and plastic stent ( HR=1.87, 95% CI:1.21-2.90, P=0.005) were independent predictors for overall survival time. Conclusion:Hepatocellular carcinoma involving the hilar bile duct has a poor prognosis. Compared with plastic stents, metal stents show advantages in clinical success rate and incidence of postoperative cholangitis. Hepatic drainage volume <30% is an independent predictor for stent patency, and Bismuth type Ⅳ, Child-Pugh class C and plastic stent are independent predictors for overall survival time.

Objective:To retrieve and summarize evidence on non-pharmacological sleep management in adult critically ill patients, providing reference for sleep intervention by ICU medical and nursing staff.Methods:The literature on non-pharmacological sleep management in adult critically ill patients was systematically searched in domestic and foreign databases and guideline websites. The search period was from the establishment of the database to February 2023. After screening the literature based on inclusion and exclusion criteria, two evidence-based trained researchers independently evaluated the quality of the included literature, extracted and summarized evidence.Results:A total of 13 articles were included, including 3 clinical guidelines, 9 systematic reviews, and 1 randomized controlled trial. A total of 21 best pieces of evidence were summarized, covering 5 aspects, including strengthening nurse education and training, improving ward environment, reducing sleep interruption, selecting mechanical ventilation modes reasonably, and promoting physical and mental relaxation.Conclusions:The evidence summarized can provide reference for the development of non-pharmacological sleep management plans for adult critically ill patients. ICU medical and nursing staff should carefully apply evidence in clinical practice based on evidence, fully consider the human resources and actual situation of the department, and combine it with the needs of patients.