Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective To investigate the changes in blood microbiota in patients with high altitude polycythemia(HAPC)and the correlation with the risk of HAPC.Methods A cross-sectional trial was carried out among 41 HAPC patients(HAPC group)and 41 healthy plateau individuals(control group)who took physical examination in the Health Management Department of No.953 Hospital of PLA Army in 2021.High-throughput sequencing technology was used to detect the V3-V4 variable region of the 16S ribosomal RNA(16S rRNA)gene in the blood smaples,and the composition and difference of the blood microbiota were compared and analyzed between the 2 groups.Results All the participants were male and Han people,and there were no significant differences in baseline data such as age,body mass index and plateau migration time between the 2 groups(P＞0.05).The α-diversity of blood microbiota in the HAPC group,including the Simpson index(0.931±0.005 vs 0.907±0.008,P＜0.05),Goods Coverage index(0.998±0.001 vs 0.997±0.001,P＜0.001)and Pielou index(0.597±0.011 vs 0.567±0.009,P＜0.05)were significantly higher than those in the control group.Meanwhile,obvious difference was observed in the β diversity between the 2 groups(P＜0.01).The relative abundance analysis of bacteria showed that Pelomonas(0.046±0.004 vs 0.033±0.003,P＜0.05),Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01),Acidovorax(0.032± 0.003 vs 0.019±0.002,Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01)and Acidovorax(0.032± 0.003 vs 0.019±0.002,P＜0.05)were statistically higher in the HAPC group than the control group.LEfSe analysis showed that the characteristic blood microbiota of the HAPC group were α-Proteobacteria,and those of control group were Trichospiridae.Conclusion Significant changes are found in diversity,relative abundance and characteristic bacteria of the blood microbiota between the HAPC patients and healthy people at the high altitude,which might be closely associated with the occurrence and development of HAPC.

High Altitude Military Hygiene is the professional core course of high-altitude medicine, which is significant to the cultivation of military medical talents urgently needed by plateau troops. Under the background of "golden course" construction and army curriculum reform, aiming at the problems such as outdated content of course materials, single teaching mode and insufficient capacity of practical courses, we actively explored the effective path of "golden course" construction, including the renovation of the curriculum-construction concept, the optimization and reorganization of the teaching content, the expansion of case teaching and equipment teaching methods, and the implementation of curriculum ideological and political education and examination reforms. The reform has further improved the learning effect of students and the level of curriculum construction, and also provided beneficial reference for the construction of similar courses in military colleges and universities.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

Objective:To observe the clinical characteristics of esophageal reflux after total gastrectomy (ERATG), and to explore the mechanism of occurrence.Methods:Fourteen gastric cancer patients who underwent total gastrectomy were prospectively enrolled in this study. The postoperative symptoms were observed and recorded and 24 h MII-pH with pH monitoring was performed to investigate the characteristics of postoperative reflux.Results:After total gastrectomy patients were with different degrees of ERATG as heartburn, appetite loss, chest tightness and belching. The overall nature of ERATG is mainly weak acid, with a pH between 4 and 7. ERATG involved esophageal-jejunal anastomosis and a length of esophagus 7 cm above the anastomosis. Patients with typical reflux symptoms had a lower pH minimum in the upright position than those without typical symptoms[(4.76±0.71) vs.(5.68±0.37), t=2.866, P<0.05]. Patients with typical reflux symptoms had a higher frequency of reflux of mixed liquid and liquid-air reflux than those without typical symptoms[liquid(31.25±29.76) vs.(4.50±9.14), t=0.011, P<0.05; liquid-air(19.50±12.99) vs.(2.00±2.61), t=0.004, P<0.05]. Conclusion:ERATG is mainly a upward reflux of weakly acidic gas, with typical symptoms of heartburn, appetite loss, chest tightness and belching. Patients with typical symptoms usually have lower pH in the upright position.

Objective To study the relationship of the tibial plateau subchondral trabecular bone (STB) microstructure and the cartilage degeneration with the lower limb alignment based on individual trabecula segmentation (ITS) and histology analysis in knee osteoarthritis (OA). Methods Hip-knee-ankle (HKA) angles were measured on the full-length lower extremity films of patients before total knee arthroplasty (TKA). The tibial plateau excised from the TKA were collected for micro-CT scanning and ITS analysis. The cartilage degeneration was evaluated by histology. The relationship between the HKA angle and the changes in microstructural parameters of STB and cartilage degeneration were analyzed. ResultsThe plate, rod and axial bone trabecular volume fraction (BV/TV, pBV/TV, pBV/TV), ratio of trabecular plate versus rod (P/R), plate trabecular number density (pTb.N), plate trabecular thickness (pTb.Th), trabecular plate surface area (pTb.S), trabecular rod length (rTb.L), and plate-plate and plate-rod junction density (P-P Junc.D, P-R Junc.D) of the subchondral bone of the tibial plateau were significantly related to the cartilage degeneration OARSI score and the HKA angle. The greater the deviation of the lower limb alignment, the greater the number of subchondral trabeculae, the thicker the trabeculae, the greater the bone mass, the stronger the connectivity, especially the plate trabeculae on the affected side of tibial plateau, and the higher the OARSI score of cartilage degeneration. Conclusions Abnormal lower limb alignment may cause abnormal microstructure of the plate and rod STB of the tibial plateau by changing the stress distribution of the knee, especially the significant increase and thickening of the plate trabecular and axial trabecular bone, which may be an important risk factor that further aggravates the degeneration of articular cartilage and the progress of OA. Therefore, lower limb alignment correction with surgical intervention and improving STB with bone metabolism agents may efficiently contribute to preventing cartilage damage and mitigate OA progression.

BACKGROUND: Lumbar disc herniation is a common clinical disease, and its pathological basis is disc degeneration. Long-term mechanical load is considered to be an important cause of lumbar disc degeneration. Because the occurrence of lumbar disc herniation is strongly associated with its mechanical state, it is necessary to further study the stress/strain behavior in the lumbar disc to provide inspiration for preventing lumbar disc herniation. OBJECTIVE: To analyze the effect of fatigue loading on mechanical properties of the whole and different regions of the intervertebral disc. METHODS: The freshly slaughtered sheep lumbar intervertebral discs L1-L2, L3-L4, and L5-L6 were obtained and made into experimental samples. The experimental samples were fixed on the experimental platform through the upper and lower vertebrae, and a quasi-static compression-cyclic loading compression-quasi-static compression experiment was performed. The L3-L4 motion segment was cut parallel to the sagittal plane, and the non-contact digital image correlation technique was used to record the internal deformation of the lumbar disc during compression. RESULTS AND CONCLUSION: (1) The results showed that all lumbar intervertebral discs exhibited non-linear load-displacement and stress-strain characteristics. (2) Effect of fatigue loading: The Young’s modulus of the lumbar intervertebral disc increased significantly after fatigue loading. (3) Impact of segment changes: The Young’s modulus changed with segment changes as follows: L5-L6 segments < L3-L4 segments < L1-L2 segments. (3) Effect of loading rate: Comparing the mechanical properties under the compression rate of 0.01 mm/s and 0.1 mm/s, it could be seen that with the increase of the compression rate, the Young’s modulus of the intervertebral disc increased significantly. (5) Internal displacement distribution: Fatigue loading had a significant effect on the internal displacement distribution of the lumbar disc under compression. Before fatigue loading, the axial displacement in upper afferent fiber was largest, and the radial displacement in inner afferent fiber was slightly smaller than that in outer afferent fiber. After fatigue loading, the axial displacement in upper afferent fiber was smallest, and the radial displacement in inner afferent fiber was significantly smaller than in outer afferent fiber. (6) The research work in this article has important theoretical guiding significance for preventing lumbar disc herniation in daily life.

Objective To investigate the clinical features and T lymphocytes subsets in patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) infection.Methods A total of 48 hospitalized patients with human immunodeficiency virus (HIV)-1/AIDS and CMV infections were recruited at Peking Union Medical College Hospital from Jan 2010 to Aug 2017.Their clinical features and immune function were retrospectively analyzed.Patients with only HIV/AIDS in previous study were recruited as controls,Results All 48 patients were at C3 stage,including 36 men and 12 women.Five of them were younger than 30 years old,33 cases within 31-50 years old,and 10 cases older than 50 years old.Thirty-five patients had CD4+T lymphocytes ≤ 50 cells/μl,7 cases with CD4+T cells 51-100/μl,3 cases with 101-200 cells/μl,and 3 cases over 200 cells/μl.As to CMV infections,there were 31 cases of CMV viremia,1 case of CMV encephalitis,1 case of CMV enteritis,5 cases of CMV pneumonia,and 9 cases of CMV retinitis.Other opportunistic infections were also common including 16 cases of pneumocystis pneumonia,9 cases of tuberculosis,5 cases of syphilis,18 cases of digestive tract fungal infections,8 cases of pulmonary fungal infections,2 cases of EB virus infections,2 cases of HIV encephalopathy/progressive multifocal leukoencephalopathy (PML),3 cases of cryptococcal meningitis,1 case of toxoplasma infection.In group of both CMV and HIV/AIDS infections,100％ patients had inverted CD4+/CD8+ ratio.The immune activation marker CD8+CD38+/CD8+ was higher (61.6％-98.8％) with a median value of 91.2％ in 40 patients.HLA-DR+ CD8+/CD8+,another marker for T cell activation,was 25.5％-98.0％ in 44 patients with a median value of 60.3％.Thirty-six patients had both immune activation markers positive.There was no significant difference in counts of B cells,natural killer cells,CD4+ T cells,CD8+ T cells and immune activation subsets stratified by gender and age (P＞0.05).Meanwhile,neither serum HIV viral load nor serum CMV viral load was correlated with HLA-DR+CD8+/CD8+,CD8+CD38+/CD8+,CD4+T cell counts,and CD4+/CD8+ ratio in the CMV and HIV/AIDS co-infection group(all P＞0.05),while HIV viral load in HIV/AIDS only group was significantly correlated with HLA-DR+CD8+T/CD8+,CD38+CD8+/CD8+,CD4+ T cell counts,CD4+/CD8+ ratio (r=0.473,0.575,-0.767 and-0.678,respectively,all P＜0.05).Conclusions CMV infections develop in HIV patients with advanced stage.CMV infection can cause life-threatening multiple organ lesions,especially in those with CD4+ T cells less than 100 cells/μl.It is of great importance to screen CMV-IgM,pp65 antigen,CMV DNA to make early diagnosis and treatment.

Objective Doppler ultrasonography was used to screen the incidence of central venous catheter (CVC) thrombosis in severe patients to observe the incidences of catheter-related thrombosis (CRT) at subclavian (SC) and internal jugular (IJ) venous insertion sites, and to analyze the factors affecting the thrombosis. Methods One hundred and twenty three adult patients with IJ or SC CVC admitted to the Department of Intensive Care Unit (ICU) of Zhongnan Hospital of Wuhan University from May to December 2015 were enrolled to be the research objects, they were divided into an IJCVC group (35 cases) and a SCCVC group (88 cases) according to different catheterization sites; they were divided into an operation group (85 cases) and a non-operation group (38 cases) according to whether operation was performed or not; and they were also divided into an anticoagulation group (25 cases) and a non-anticoagulation group (98 cases) according to whether anticoagulation therapy was used or not. Doppler ultrasonography was performed every day to observe the incidences of CRT during ICU stay. Results One hundred and twenty-three patients were included in this study. CRT was detected in 11 (8.9%) patients, with an incidence of 22.1 per 1 000 catheter-days. All the 11 cases with CRT were presented within 3 days after the insertion, with 9 cases (81.8%) on the first day and 2 cases (18.2%) on the third day. The incidence of CRT in SCCVC group was significantly lower than that in IJCVC group [5.7% (5/88) vs. 17.1% (6/35), P < 0.05], with the rates of 12.6 and 59.4 per 1 000 catheter-days, respectively. There were no statistical significant differences in the incidences of CRT between operation group and non-operation group [11.8% (10/85) vs. 2.6% (1/38)], and between anticoagulation group and non-anticoagulation group [8.0% (1/25) vs. 9.2% (2/98), both P > 0.05]. Conclusions The incidence of CRT at IJCVC site is estimated to be 3-times higher than that at SCCVC site, anticoagulants or surgical operation may have impacts on the incidence of CRT, although there were no statistically significant differences. The CRT usually occurs within 3 days after the catheter insertion. Frequent bedside ultrasonography in the first 3 days after catheterization can confirm the diagnosis and guide clinical treatment.