Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

OBJECTIVE: To explore the potential causal relationship between intervertebral disc degeneration and certain autoimmune diseases. METHODS: Genome-wide association study (GWAS) data of 5 autoimmune diseases were obtained from large-scale GWAS databases. Data on internal vertebral disc degeneration (IVDD) were derived from the FinnGen consortium, which included 294, 770 controls and 41, 669 cases. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the potential causal relationship between the 5 autoimmune diseases and IVDD. Multiple analytical methods were adopted, including MR methods such as inverse variance weighting(IVW), MR-Egger, weighted median, weighted mode, and simple mode. Cochran's Q test, leave-one-out analysis, and MR-Egger intercept test were conducted to assess heterogeneity, robustness, and pleiotropy. For the robustness of the results, MR-PRESSO was used to detect outliers, and MR analysis was re-conducted after removing the outliers. RESULTS: The MR analysis results showed that there might be a bidirectional causal relationship between ankylosing spondylitis(AS) and IVDD:AS on IVDD, OR=1.038, 95%CI (1.024, 1.053), P=0.000;and IVDD on AS, OR=2.117, 95%CI(1.065, 4.207), P=0.032. There might be a positive correlation between IVDD and rheumatoid arthritis(RA) as well as systemic lupus erythematosus(SLE):IVDD on RA, OR=1.184, 95%CI(1.071, 1.309), P=0.001;and IVDD on SLE, OR=1.678, 95%CI(1.187, 2.372), P=0.003. There was no significant correlation between ulcerative colitis(UC), autoimmune thyroiditis(ATD) and IVDD. After removing outliers by MR-PRESSO and re-conducting MR analysis, the results did not change qualitatively. Sensitivity analysis indicated that the results were robust to potential sources of bias. CONCLUSION AS and IVDD may be risk factors for each other, and IVDD may be a potential risk factor for RA and SLE. These findings provide a basis for guiding the prevention and combined diagnosis and treatment of IVDD, AS, RA, and SLE, while the specific underlying mechanisms still require further experimental basic research.
Humans ; Intervertebral Disc Degeneration/etiology* ; Mendelian Randomization Analysis ; Autoimmune Diseases/complications* ; Genome-Wide Association Study ; Spondylitis, Ankylosing/genetics* ; Arthritis, Rheumatoid/genetics*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10％L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9％NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P＜0.05,P＜0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P＜0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens up new possibilities for treatment.

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Purpose/Significance To identify research frontiers in the field,so as to assist scientific researchers to effectively select and track key research topics,and help research management decision-makers to dynamically adjust policy orientation.Method/Process Taking 37 927 pieces of high-impact journal document references and highly cited document references from the WOS database which published in the period of 2012-2022 as the data samples,BERTopic is used to extract topics,a multi-dimensional indicator re-search frontier recognition model is constructed,and different types of research frontiers in the field are identified from multiple dimen-sions.Result/Conclusion The proposed model identifies 9 hot research frontier topics,14 emerging research frontier topics,13 potential research frontier topics and 1 declining research topic in the field of oncology,which is effective.