ObjectivesTo analyze the trends in mortality and disease burden of colorectal cancer (CRC) among the registered residents in Danyang City, Jiangsu Province, from 2013 to 2023, and to provide a scientific basis for developing CRC prevention and control strategies. MethodsMortality surveillance data on CRC among the registered residents in Danyang City from 2013 to 2023 were collected and analyzed. Crude mortality rate (CMR), age-standardized mortality rate (ASMR), years of life lost (YLL) due to premature death, and YLL rate were calculated. The annual percentage change (APC) and average annual percent change (AAPC) of CMR, ASMR and YLL rate were calculated with Joinpoint Regression Program 4.9.0.1. ResultsA total of 1 920 deaths from colorectal cancer were recorded in Danyang City during 2013‒2023, with an average annual CMR of 21.75/100 000, which showed an upward trend (APC=6.47%, 95%CI: 4.21%‒8.79%, P<0.001), with higher CMR observed in males than that in females. The overall ASMR by Chinese standard population was 12.10/100 000, with no obvious temporal trends (APC=1.37%, P=0.364). ASMR increased with age, particularly after 45 years. The total YLL due to CRC was 34 711 person-years, with an average YLL rate of 3.93‰. The YLL rate showed a significant upward trend from 2013 to 2023 (APC=4.96%, 95%CI: 4.08%‒18.16%, P<0.001) in Danyang City. ConclusionThe mortality rate of colorectal cancer in Danyang City is relatively high and has shown a rising trend, resulting in an increasing disease burden on the residents year by year. Continued efforts to strengthen CRC prevention and control are needed, particularly targeting males and the elderly population.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

The identification and optimization of mutations in nanobodies are crucial for enhancing their therapeutic potential in disease prevention and control. However, this process is often complex and time-consuming, which limit its widespread application in practice. In this study, we developed a workflow, named Evolutionary-Nanobody (EvoNB), to predict key mutation sites of nanobodies by combining protein language models (PLMs) and molecular dynamic (MD) simulations. By fine-tuning the ESM2 model on a large-scale nanobody dataset, the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced. The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies. Additionally, we selected four widely representative nanobody-antigen complexes to verify the predicted effects of mutations. MD simulations analyzed the energy changes caused by these mutations to predict their impact on binding affinity to the targets. The results showed that multiple mutations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target, further validating the potential of this workflow for designing and optimizing nanobody mutations. Additionally, sequence-based predictions are generally less dependent on structural absence, allowing them to be more easily integrated with tools for structural predictions, such as AlphaFold 3. Through mutation prediction and systematic analysis of key sites, we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes. The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Objective To understand the epidemiological characteristics of Chlamydia trachomatis infection in Hubei province, and to provide scientific basis for prevention and control. Methods The data of Chlamydia trachomatis infection cases reported through the China Information System for Disease Control and Prevention from 2008 to 2022 were collected for epidemiological statistical analysis. Results The incidence of Chlamydia trachomatis infection in Hubei Province showed an increasing trend from 2008 to 2022, with an average annual reported incidence of 2.26/100 000. The top three reported incidence areas were Shiyan (6.04/100 000), Yichang (5.62/100 000) and Shennongjia (3.47/ 100 000). The reported incidence in southeast area was significantly higher than that in other areas (χ²=2869.603 , P < 0.001). The high incidence age group was 20-39 years old, accounting for more than 70%. The reported incidence in females was higher than that in males (χ²=1429.27 , P < 0.001). Housework and unemployment were the most common professions (43.54%). The case reporting institutions were mainly comprehensive hospitals (87.29%). Conclusion To effectively control the infection and transmission of Chlamydia trachomatis, it is necessary to strengthen the health popularization of STD knowledge, intervention and early active screening of high-risk groups.

By consulting the ancient and moderm literature， this paper makes a textual research on the name， origin， quality evaluation， harvesting and processing of Olibanum， so as to provide a basis for the development of the famous classical formulas containing this medicinal material. According to the herbal textual research， the results showed that Olibanum was first described as a medicinal material by the name of Xunluxiang in Mingyi Bielu（《名医别录》）， until Ruxiang had been used as the correct name since Bencao Shiyi（《本草拾遗》） in Tang dynasty. The main origin was Boswellia carterii from Burseraceae family. The mainly producing areas in ancient description were ancient India and Arabia， while the modern producing areas are Somalia， Ethiopia and the southern Arabian Peninsula. The medicinal part of Olibanum in ancient and modern times is the resin exuded from the bark， which has been mainly harvested in spring and summer. It is concluded that the better Olibanum has light yellow， granular， translucent， no impurities such as sand and bark， sticky powder and aromatic smell. There were many processing methods in ancient times， including cleansing（water flying， removing impurities）， grinding（wine grinding， rush grinding）， frying（stir-frying， rush frying， wine frying）， degreasing， vinegar processing， decoction. In modern times， the main processing methods are simplified to cleansing， stir-frying and vinegar processing. Nowadays， the commonly used specifications include raw， fried and vinegar-processed products. Among the three specifications， raw products is the Olibanum after cleansing， fried products is a kind of Olibanum processed by frying method， vinegar-processed products is the processed products of pure frankincense mixed with vinegar. Based on the research results， it is recommended to select the resin exuded from the bark of B. carterii for the famous classical formulas such as Juanbitang containing Olibanum， processing method should be carried out in accordance with the processing requirements of the formulas， otherwise used the raw products if the formulas without clear processing requirements.

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

Palliative care not only embodies modern life perspectives, but also encompasses significant traditional Chinese cultural elements.The primary objective of palliative care is to alleviate patient suffering, preserve their dignity, and facilitate a peaceful passing.Traditional Chinese medicine, known for its simplicity, accessibility, affordability, and efficacy in disease prevention and treatment, adopts a holistic approach to address systemic pain through personalized treatment based on symptom differentiation.This approach aims to enhance the quality of life for terminally ill patients.To equip palliative care providers with essential clinical skills in traditional Chinese medicine, the National Center of Gerontology and Beijing Palliative Care Guidance Center collaborated with experts and scholars to develop guidelines focusing on common end-of-life symptoms.Through extensive deliberation, expert evaluation, and revisions, this guidance document was crafted as a valuable resource for palliative care practitioners, traditional Chinese medicine clinicians, and researchers in the field.

Objective:To compare the efficacy, dosage, and safety of dupilumab combined with minocycline or with minocycline and systemic glucocorticoids (sGC) versus minocycline alone or in combination with sGC in patients with bullous pemphigoid (BP) .Methods:A retrospective cohort study was conducted on BP patients who visited the Department of Dermatology, Peking University First Hospital from March 2021 to June 2022 and were treated with one of the following two therapeutic regimens: minocycline alone or in combination with sGC (M-MG group), and dupilumab combined with minocycline or with minocycline and sGC (MD-MGD group). Disease control rates, time to disease control, complete remission rates, time to complete remission, BP disease area index (BPDAI) scores, drug usage, time to pruritus relief, relapse rates, and occurrence rates of adverse reactions were compared between the two groups. Survival analysis was performed using Kaplan-Meier (KM) curves and Log-rank test. Confounders were controlled by 1∶1 matching on the propensity score in the two groups.Results:A total of 164 patients were collected, including 110 in the M-MG group (62 males and 48 females, aged 74.6 ± 12.8 years) and 54 in the MD-MGD group (33 males and 21 females, aged 74.6 ± 13.3 years). After two-week follow-up, there was no significant difference in the disease control rate between the two groups ( P = 0.341); however, the minocycline dose, proportion of patients using sGC, sGC dose, and cumulative sGC dose were all significantly higher in the M-MG group than in the MD-MGD group (all P < 0.05). A total of 152 patients (92.7%) achieved disease control in the two groups during the follow-up, while the disease control rate and time to disease control did not differ between the two groups (both P > 0.05); 52 patients (31.7%) achieved complete remission, there was no significant difference in the complete remission rate between the MD-MGD group (16/54, 29.6%) and M-MG group (36/110, 32.7%; χ2 = 0.16, P = 0.689), but the time to complete remission ( M[ Q1, Q3]) was significantly shorter in the MD-MGD group (98.5[78.0, 185.2] days) than in the M-MG group (223.5 [175.2, 277.0] days, P = 0.001). KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.024). A total of 73 patients (44.5%) recorded the time to pruritus relief during the follow-up, and the MD-MGD group showed significantly shorter time to pruritus relief (54 patients, 14.0 [3.0, 14.0] days) compared with the M-MG group (19 patients, 14.0 [7.0, 19.0] days; P = 0.015). After propensity score matching, each group included 42 patients; during the follow-up, there was no significant difference in the complete remission rate between the M-MG group and MD-MGD group ( P > 0.05), but the time to complete remission was significantly longer in the M-MG group than in the MD-MGD group ( P = 0.019); KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.041). Among the 164 patients, adverse reactions occurred in 58 (35.4%), grade 3 or more severe adverse reactions occurred in 11 (6.70%), but no dupilumab-related adverse reactions were reported. Conclusions:Compared with minocycline alone or in combination with sGC in the treatment of BP, the dupilumab combination therapy could relieve pruritus and result in complete remission in a shorter time. Additionally, dupilumab could help to accelerate the reduction in dosages of sGC and minocycline, with few adverse reactions and favorable safety.