Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

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Objective:To correlate blood lipids and body mass index (BMI) with Helicobacter pylori (Hp) infection. Methods:A total of 303 participants who underwent physical examinations at The 903 Hospital of PLA Joint Logistics Support Force from May 2022 to May 2023 were included in this case-control study. These patients were divided into an Hp-infected group ( n = 97) and a non-Hp-infected group ( n = 206) based on whether they had Hp infection or not. Participants' body height and weight were recorded, and BMI was calculated. The levels of four blood lipid indicators were determined using an automatic biochemical analyzer. The distribution of different BMIs and abnormal statuses of these four blood lipid indicators were compared between the two groups. Spearman correlation analysis was used to analyze the correlation between Hp infection and these four blood lipid indicators. A multivariate logistic regression model was applied to analyze the influential factors for Hp infection. Results:The number of participants who had 24 kg/m 2 ≤ BMI < 28 kg/m 2 [39.17% (38/97)] and the number of participants who had BMI ≥ 28 kg/m 2 [10.31% (10/97)] in the Hp-infected group was significantly higher than those in the non-Hp-infected group [19.90% (41/206) and 2.43% (5/206), χ2 = 12.71, 7.11, P < 0.001, 0.008]. The decrease rate of high-density lipoprotein cholesterol (HDL-C), increase rate of low-density lipoprotein cholesterol (LDL-C), increase rate of triglyceride (TG), and increase rate of total cholesterol (TC) in the Hp-infected group were 23.71% (23/97), 31.96% (31/97), 17.53% (17/97), and 22.68% (22/97), respectively, which were significantly higher than 9.22% (19/206), 11.17% (23/206), 7.28% (15/206), and 8.74% (18/206) in the non-Hp-infected group ( χ2 = 11.59, 19.47, 7.33, 11.19, P = 0.001, < 0.001, 0.007, 0.001). The Spearman analysis showed that Hp infection was linearly positively correlated with BMI, LDL-C, TG, and TC ( r = 0.571, 0.519, 0.473, 0.535, all P < 0.001), while it was linearly negatively correlated with HDL-C ( r = -0.628, P < 0.001). Multivariate logistic regression analysis showed that BMI ≥ 24 kg/m 2, decreased HDL-C, increased LDL-C, elevated TG, and elevated TC are independent risk factors for Hp infection. Conclusion:Blood lipids and BMI are closely associated with Hp infection, and abnormal blood lipids and elevated BMI are independent risk factors for Hp infection.

Objective To evaluate the effectiveness,safety and economy of the clinical application of levetiracetam(LEV)concentrated solution for injection generic drug and the original drug in the national centralized volume-based procurement.Methods The information of inpatients using original LEV concentrated solution for injection in the Xuanwu Hospital of Capital Medical University(original drug group)and inpatients using generic LEV concentrated solution for injection in the First Affiliated Hospital of Wannan Medical College(generic drug group)was retrospectively analyzed after the implementation of the procurement policy(from November 2021 to March 2022).To compare the effectiveness,safety and economy of the two in the prevention and treatment of epilepsy.Results In the original drug group and the generic drug group,18 and 17 patients were enrolled in the treatment of epilepsy respectively,the effective rates were 50.00％and 58.82％,the incidence of adverse reactions were both 0％,and the median daily cost was 255.00(255.00,510.00)yuan and 131.78(131.78,131.78)yuan.After propensity score matching,both the original drug group and the generic drug group had 76 patients each received preventive medication,the effective rates were 97.37％and 100％(P＞0.05),and the incidence of adverse reactions were both 0％.The median daily fee for the original the generic drug group was 170.00(170.00,170.00)yuan and 131.78(131.78,131.78)yuan,there were significant difference(P＜0.01).Conclusion The clinical effect of generic and original LEV concentrated solution for injection in preventing epilepsy is basically the same,the clinical safety are equivalent,the generic has better economy than the original.The effective rate of the treatment of epilepsy is similar,while the sample size needs to be further expanded to verify the results.

Objective:To investigate the effects of montelukast sodium combined with compound methoxyphenamine on airway inflammation, intercellular adhesion molecule-1 (ICAM-1), toll-like receptor 4 (TLR4), and soluble programmed death ligand 1 (sPD-L1) levels in patients with post-infection cough.Methods:A total of 200 patients with post-infection cough who received treatment at The 903 Hospital of the PLA Joint Logistics Support Force from January to December 2023 were included in this randomized controlled study. The patients were divided into an observation group ( n = 100) and a control group ( n = 100) using the random number table method. The control group received oral administration of compound methoxyphenamine capsules, while the observation group received oral administration of montelukast sodium in addition to compound methoxyphenamine capsules. Both groups were treated for 7 days. The therapeutic effects as well as daytime and nighttime cough scores, airway inflammation change, serum ICAM-1, TLR4, and sPD-L1 levels, and Leicester Cough Questionnaire scores were compared between the two groups. Results:The total effective rate in the observation group was 95% (95/100), which was significantly higher than that in the control group [84% (84/100), Z = 2.49, P < 0.05]. After treatment, the daytime and nighttime cough scores in the observation group were (1.24 ± 0.31) points and (1.02 ± 0.31) points, respectively, which were significantly lower than those in the control group [(2.17 ± 0.65) points, (1.94 ± 0.47) points, t = 12.91, 16.34, both P < 0.001]. Serum levels of hypersensitive C-reactive protein, interleukin-8, tumor necrosis factor-alpha in the observation group were (8.84 ± 2.21) mg/L], (82.34 ± 13.24) mg/L, and (78.94 ± 13.24) ng/L, respectively, which were significantly lower than those in the control group [(12.76 ± 2.53) mg/L, (127.18 ± 35.17) mg/L, (102.31 ± 21.08) ng/L, t = 11.67, 11.93, 9.39, all P < 0.001]. The ICAM-1 and TLR4 levels in the observation group were (178.32 ± 21.23) μg/L and (7.45 ± 2.32) ng/L, respectively, which were significantly lower than those in the control group [(247.18 ± 25.64) μg/L, (19.98 ± 4.53) ng/L, t = 20.69, 24.62, both P < 0.001], while sPD-L1 level in the observation group [(2.34 ± 0.37) ng/L] was significantly higher than that in the control group [(1.72 ± 0.41) ng/L, t = -11.23, P < 0.001]. The quality-of-life scores in the observation group for social [(2.61 ± 0.25) points], psychological [(6.56 ± 0.45) points], physical [(7.65 ± 0.72) points], and total score [(16.81 ± 2.51) points] were significantly higher than those in the control group [(2.14 ± 0.30) points, (5.44 ± 0.52) points, (6.07 ± 0.65) points, (13.74 ± 2.68) points, t = 12.04, 16.29, 16.29, 8.36, all P < 0.001]. Conclusion:Montelukast sodium combined with compound methoxyphenamine is highly effective in treating post-infection cough in patients. The combined therapy can reduce airway inflammation, lower ICAM-1 and TLR4 levels, and increase sPD-L1 levels.

Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8⁺ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8⁺ and TIGIT⁺CD8⁺ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT⁺CD8⁺ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT⁺CD8⁺T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8⁺ and TIGIT⁺CD8⁺ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT⁺CD8⁺ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT⁺CD8⁺ T cells from the normal mice. The percentages of TIGIT⁺CD8⁺ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT⁺CD8⁺ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
Animals ; Mice ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Interferon-gamma/metabolism* ; Interleukin-10/metabolism* ; Interleukin-17/metabolism* ; Interleukin-4/metabolism* ; Lung/metabolism* ; Malaria/metabolism* ; Plasmodium yoelii/metabolism* ; Programmed Cell Death 1 Receptor/metabolism*

To evaluate the association between serum anti-tissue transglutaminase antibody (anti-tTG) titers and the severity of histological damage to the duodenal mucosa and to predict a possible anti-tTG cutoff value for diagnosing celiac disease (CD) and villous atrophy in the domestic population. Clinical and pathological data from 76 adult CD patients with positive anti-tTG titers and duodenal biopsy results who were treated at the People′s Hospital of Xinjiang Uygur Autonomous Region from July 2017 to January 2022 were retrospectively analyzed. The correlation between anti-tTG titers and the severity of duodenal mucosal damage was statistically assessed to predict the optimal anti-tTG titer cut-off value for diagnosing CD and villous atrophy. Of the 76 patients, 10 had underlying CD, and of the 66 patients with duodenal histopathology, four were Marsh Ⅰ, six were Marsh Ⅱ, and 56 were Marsh Ⅲa-c grade. In adults with CD, anti-tTG titers were shown to be associated with the severity of histological damage to the duodenal mucosa. When the anti-tTG level was ≥5 times the upper limit of normal (ULN), the sensitivity and specificity for diagnosing CD were 83.9% and 92.9%, respectively. When the anti-tTG titer was ≥8 times the ULN, the sensitivity and specificity for diagnosing villous atrophy were 67.9% and 90.0%, respectively. Anti-tTG levels had a strong predictive value for diagnosing CD in adults when titers exceeded 10 times the ULN. Thus, the anti-tTG cut-off value can be combined with clinical judgment to diagnose CD, limiting the use of invasive endoscopy.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans ; Fecal Microbiota Transplantation ; Complement C3 ; Convalescence ; Prospective Studies ; Feces

Objective : To investigate the effects of 3 types of trihalomethanes ( THMs) , the by⁃products in treatment of drinking water disinfection , on the development and reproductive capacity of germ cells of Caenorhabditis elegans. Methods : Tribromomethane ( TBM) , trichloromethane ( TCM) and triiodomethane ( TIM) , 3 types of THMs were selected and wild type Caenorhabditis elegans was used as a model to detect germ cell apoptosis , oocyte number and the final brood size after exposure to different concentrations of THMs. Results : The results of germ cell apoptosis showed that the exposure to 50 μmol/L TCM and TIM caused elevated levels of germ cell apoptosis in a dose⁃dependent manner. Oocyte counting results showed that exposure to 50 μmol/L all three THMs significantly reduced the number of oocytes. The brood size results showed that only 50 μmol/L TIM exposure significantly de⁃ creased the brood size of nematodes. Conclusion THMs showed negative impacts on the reproductive system of Caenorhabditis elegans , and the toxicity is related to the halogenated elements of THMs.