Objective To explore the potential causal links between micronutrient levels and the risk of immune-mediated inflammatory skin disease(IMID).Methods Leveraging publicly accessible genome-wide association study(GWAS)datasets,fifteen specific micronutrients were identified as exposure variables,while four prevalent IMID:Psoriasis,atopic dermatitis,urticaria,and alopecia areata were designated as study outcomes.Robust instrumental variables were meticulously selected to facilitate the Mendelian randomization analysis.The main assessment used the inverse-variance weighting(IVW)method,complemented by an assortment of Mendelian randomization methodologies,inclusive of MR-Egger,weighted median estimate(WME)and weighted mode(WM).Rigorous sensitivity analyses were conducted to bolster the robustness of the findings.Results Vitamin D exhibited a significant inverse association with the risk of psoriasis(OR=0.996,P=0.001,95％CI:0.994-0.998),corroborated by consistent trends across WME,MR-Egger,and WM methods.Phosphorus demonstrated a positive correlation with urticaria risk(OR=5.634,95％CI:1.792-17.711,P=0.003),with findings in alignment with WME and WM methods.Copper was found to be positively associated with atopic dermatitis risk(ORIVW=1.234,P=0.0007,95％CI:1.092-1.394),and vitamin E levels were significantly related to the risk of urticaria(OR=26.643,P=0.013,95％CI:1.981-358.333).Sensitivity analysis did not show heterogeneity and pleiotropy(P＞0.05).Conclusion The study establishes a causal relationship between vitamin D levels and the risk of psoriasis,suggesting that augmenting vitamin D intake could be a viable dietary intervention for psoriasis prevention.These findings offer novel insights into the preventative and therapeutic strategies for IMID.

Objective To explore the potential causal links between micronutrient levels and the risk of immune-mediated inflammatory skin disease(IMID).Methods Leveraging publicly accessible genome-wide association study(GWAS)datasets,fifteen specific micronutrients were identified as exposure variables,while four prevalent IMID:Psoriasis,atopic dermatitis,urticaria,and alopecia areata were designated as study outcomes.Robust instrumental variables were meticulously selected to facilitate the Mendelian randomization analysis.The main assessment used the inverse-variance weighting(IVW)method,complemented by an assortment of Mendelian randomization methodologies,inclusive of MR-Egger,weighted median estimate(WME)and weighted mode(WM).Rigorous sensitivity analyses were conducted to bolster the robustness of the findings.Results Vitamin D exhibited a significant inverse association with the risk of psoriasis(OR=0.996,P=0.001,95％CI:0.994-0.998),corroborated by consistent trends across WME,MR-Egger,and WM methods.Phosphorus demonstrated a positive correlation with urticaria risk(OR=5.634,95％CI:1.792-17.711,P=0.003),with findings in alignment with WME and WM methods.Copper was found to be positively associated with atopic dermatitis risk(ORIVW=1.234,P=0.0007,95％CI:1.092-1.394),and vitamin E levels were significantly related to the risk of urticaria(OR=26.643,P=0.013,95％CI:1.981-358.333).Sensitivity analysis did not show heterogeneity and pleiotropy(P＞0.05).Conclusion The study establishes a causal relationship between vitamin D levels and the risk of psoriasis,suggesting that augmenting vitamin D intake could be a viable dietary intervention for psoriasis prevention.These findings offer novel insights into the preventative and therapeutic strategies for IMID.

Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P＜0.05,P＜0.001),but did not up-regulate the expression of Beclin1(P＞0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P＜0.05,P＜0.05,P＜0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulated the expression of Beclin1(P＞0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulate the expression of Beclin1(P＞0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective To investigate the effect of acupuncture at key muscle movement points combined with exercise training on neurophysiological indicators,muscle tone and quality of life in patients with spinal cord injury(SCI).Methods Eighty SCI patients admitted to the Rehabilitation Diagnosis and Treatment Center of Beijing Rehabilitation Hospital Affiliated to Capital Medical University from September 2022 to June 2024 were selected.Patients were divided into the control group(receiving routine acupuncture combined with exercise training,40 cases)and the observation group(receiving acupuncture combined with exercise training at key muscle movement points,40 cases)according to the random number table method.The neurophysiological indicators[motor nerve conduction velocity(MNCV),sensory nerve conduction velocity(SNCV)],limb function[Fugl-Meyer Assessment(FMA),Modified Ashworth Scale(MAS)]and quality of life[Barthel index,functional independence measure(FIM)]were compared between the two groups.Results After intervention,the MNCV and SNCV of median nerve,ulnar nerve,tibial nerve and common peroneal nerve were increased in the observation group than those in the control group(P＜0.05).After intervention,there were higher FMA scores,Barthel index and FIM scores in the observation group than those of the control group,while the MAS score was lower than that of the control group(P＜0.05).Conclusion Acupuncture at key muscle movement points combined with exercise training can effectively improve the neuroelectrophysiological indicators,limb functions and quality of life of SCI patients,which is feasible rehabilitation intervention program.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.

Objective:To examine the prevalence of malnutrition and evaluate the impact of nutritional support on clinical outcomes in elderly patients diagnosed with gastric and colorectal cancer.Methods:A retrospective cohort study was conducted, analyzing elderly patients with gastrointestinal tumors who underwent surgical treatment in the general surgery department from January 2019 to June 2020.The Global Leadership Initiative on Malnutrition(GLIM)criteria were utilized to diagnose malnutrition, and the effects of malnutrition and nutritional support on clinical prognosis were investigated.Results:A total of 426 elderly hospitalized patients with gastric and colorectal tumors who underwent surgical treatment were included in this study.This cohort comprised 199 cases of gastric cancer and 227 cases of colorectal cancer, with ages ranging from 65 to 91 years(mean age: 72.05±5.99).According to the GLIM criteria, 43.7%(186/426)of the patients were diagnosed with malnutrition, of which 25.6%(109/426)were moderately malnourished and 18.1%(77/426)were severely malnourished.Among the gastric cancer patients, 73.4%(146/199)were identified as having nutritional risk, with 48.7%(97/199)being malnourished and 22.6%(45/199)experiencing severe malnutrition.In the colorectal cancer group, 63.9%(145/227)were at nutritional risk, 39.2%(89/227)were malnourished, and 14.1%(32/227)had severe malnutrition.Additionally, 60.3%(257/426)of the patients received nutritional support therapy: 25.4%(108/426)received parenteral nutrition(PN), 11.3%(48/426)received enteral nutrition(EN), 23.7%(101/426)received a combination of EN and PN, while 39.7%(169/426)did not receive any nutritional support.Regardless of the presence or degree of malnutrition, patients who received nutritional support had significantly shorter total hospital stays compared to those who did not receive nutritional support, and this difference was statistically significant( t=5.58, 3.69, 2.21, 3.03, all P<0.05). Conclusions:Providing nutritional support to malnourished patients can reduce the length of hospital stay and improve clinical outcomes.

Objective To develop a size exclusion-high-performance liquid chromatography(SEC-HPLC) method for the simultaneous determination of free proteins and residual 4-dimethylaminopyridine(DMAP) in the bulk solution of pneumococcal polysaccharide-protein conjugate, and to verify and preliminarily apply the method.Methods By studying the characteristic ultraviolet absorption peak of DMAP and optimizing the separation method of chromatographic column, the SEC-HPLC method was established to realize the retention and separation of free proteins and DMAP on the same chromatographic column and quantify them. The method was verified for specificity(system suitability), limit of quantification(LOQ), accuracy, precision, linearity and range, and robustness, and was used to detect the free proteins and DMAP residues in the test sample.Results The chromatographic conditions were determined as follows: TSKgel G5000 PWXL analytical column was used as the column(7. 8 mm × 300 mm, 10 ??m), the column temperature was set at 35 ℃, the mobile phase was0. 85% sodium chloride solution, the pH was(6. 2 ± 0. 2), the flow rate was 0. 5 mL/min, and the detection wavelength was280 nm. The resolution of free protein peaks of diphtheria toxoid(DT) or tetanus toxoid(TT) and DMAP peak from adjacent peaks was greater than 1. 5. The LOQs of TT, DT and DMAP were 0. 50, 1. 20, and 0. 02 ??g/mL, respectively. The spiked recovery rates of TT, DT and DMAP were 98. 11%-104. 60%, 95. 43%-103. 26% and 97. 11%-98. 42%, respectively.The relative standard deviations(RSDs) of intermediate precision of TT, DT and DMAP were all less than 5%. The R~2 values of TT and DT were greater than 0. 999 0 in the range of 6-24 ??g/mL, and the R~2 value of DMAP was 1. 000 in the range of2-10 ??g/mL. The RSDs of TT, DT and DMAP content were all less than 3% at the injection temperature of 30, 35 and 40 ℃.The established method was used to determine the content of free proteins and DMAP in the test sample, and rapid and accurate results were obtained.Conclusion The established SEC-HPLC method has good system suitability, accuracy,precision, linear relationship and robustness, which can realize the dual quantification of free proteins and DMAP in the same experiment, and can be used to monitor the impurities in the binding process.