The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective To explore the optimal ratio of Baitong decoction based on efficacy,clarify its spectrum-effect relationship,and identify its potential quality markers.Methods An ulcerative colitis(UC)model in mice was established using dextran sulfate sodium.The efficacy of Baitong decoction with varying drug ratios was assessed by evaluating the apparent score,pathological score and inflammatory factor changes of UC in each group of experimental animals.The fingerprints of Baitong decoction with different ratios were established by high performance liquid chromatography(HPLC),and the relationship between the content of each substance and its efficacy was analyzed by partial least squares regression to determine the potential quality markers of Baitong decoction.Results Baitong decoction was most effective in relieving ulcerative colitis when the mass ratio of Fuzi,Ganjiang and Congbai was 1∶2∶2.The fingerprinting identified 14 common peaks across 7 ratios,with 9 peaks were found to be associated with the remission of ulcerative colitis by partial least squares regression analysis.Conclusion The optimal ratio of Fuzi,Ganjiang and Congbai for treating UC is 1∶2∶2.The spectrum-effect relationship analysis suggested that the quality markers of Baitong decoction may be the substances represented by peak 2(benzoylaconine),3,5,6,8(mesaconine),9(aconitine),10(hypaconitine),13(10-gingerol)and 14.

Objective:To investigate the clinical features, diagnosis, treatment, and future sex selection in patients with partial androgen insensitivity syndrome (PAIS).Methods:Retrospective analysis of clinical data of three patients with PAIS who received treatment in The Third Affiliated Hospital of Xi'an Medical University, Beijing Ditan Hospital of Capital Medical University, and Beijing Yayuncun Amcare Women's and Children's Hospital from 2013 to 2015 was conducted. Physical signs, specialized examinations, surgical explorations, and treatments were analyzed. The Chinese database was searched, and 12 cases of PAIS were collected and summarized.Results:Fifteen patients with PAIS presented with primary amenorrhea (15/15). Special clinical manifestations included gender as male or appearing as male (5/15), penile dysplasia or clitoral hypertrophy (14/15), urethral dysplasia (5/15), and breast development (4/15). Eleven cases were treated based on female gender (including surgery and hormone replacement therapy). There were three special patients with PAIS who had specific etiology, genetics, clinical manifestations, histopathology, diagnosis, and treatment and ultimately underwent treatment based on female gender.Conclusion:PAIS is a rare form of disorder of sex development, featuring a karyotype of 46, XY, and is a congenital X-linked recessive condition. Understanding the pathogenesis of PAIS more thoroughly can contribute to accurate diagnosis, personalized treatment, and well-organized follow-up, thereby preventing gender dysphoria.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective:To establish an animal model of chronic systemic inflammation with long-term high expression of circulating IL-6 by introducing exogenous IL-6 gene transfer vector.Methods:Recombinant murine IL-6-encoding adeno-associated virus (AAV-IL-6) was constructed. Twenty-one 24-week-old male C57BL/6J mice were randomly divided into three groups with seven in each group: AAV-IL-6 group, vector control (AAV-ctrl) group and blank control group. At 0, 8 and 16 weeks of intervention, the mice in the three groups were injected with AAV-IL-6 (100 μl 0.5×10 10 vp/ml), unloaded AAV (100 μl 0.5×10 10 vp/ml) and the same volume of saline in the tail vein, respectively. IL-6 levels in mouse serum were measured by ELISA. The general condition of mice was observed and blood routine tests were performed. Changes in blood biochemical parameters and C-reactive protein (CRP) levels were detected. At the end of 24-week intervention, the mice were sacrificed and the myocardium, liver, spleen, quadriceps femoris, knee joint and middle femur were taken for HE staining. Results:At 4, 8, 16 and 24 weeks after intervention, serum IL-6 levels were (75.41-169.28) pg/ml in the AAV-IL-6 group, while in the two control groups, the levels were below the lower limit of detection (7.8 pg/ml). At 24 weeks after intervention, the body weight of mice in the AAV-IL-6 group was significantly lower than that of mice in the two control groups; the neutrophil counts and CRP level in the AAV-IL-6 group were higher than those in the two control groups, while the levels of albumin, creatinine, triglyceride and cholesterol were lower than those in the two control groups. There were no differences in the aforementioned parameters between the two control groups. Compared with the blank control group, both AAV-IL-6 and AAV-ctrl groups showed increased lymphocyte counts. All mice had normal liver and kidney functions at the end of intervention. Histopathological findings indicated that the mice in the AAV-IL-6 group had focal infiltration of lymphocytes in the central venous area of the liver and around the myocardial and the skeletal muscle fibers, diffuse infiltration of multinucleated giant cells in the spleen, atrophic skeletal muscle, disorganized growth plate, reduced chondrocyte hypertrophic zone, thinner bone cortex and trabecular, and reduced osteoid. There were no histopathological changes in mice of the two control groups.Conclusions:Repeated tail vein injection of AAV-IL-6 could achieve long-term high expression of circulating IL-6 in mice, which manifested the phenotype of chronic systemic inflammation in preliminary detection and provided a safe, effective and simply accessible animal model for related studies.

Objective:To explore the trans-membrane signaling mechanism of interleukin-6 (IL-6)-induced osteogenic differentiation and calcification of human umbilical artery smooth muscle cells (HUASMCs).Methods:HUASMCs were primarily cultured in vitro and were stimulated with IL-6, IL-6+solutable IL-6 receptor (sIL-6R), IL-6+sIL-6R+solutable gp130 (sgp130), or vehicle (blank control). Alizarin red and Von Kossa staining were used for detecting cell calcification, Western blot was used to test the protein expression of tissue-nonspecific alkaline phosphatase (TNAP), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and Runt related transcription factor 2 (Runx2), and immunofluorescence was used to examine the mIL-6R expression of HUASMCs. The comparison of measurement date between the two groups was conducted by t-test. The comparison of measurement date between multiple groups was conducted by one-way analysis of variance (ANOVA). Results:The intensity severity of calcification stain was IL-6+sIL-6R group >IL-6+sIL-6R+sgp130 group>IL-6 group=blank control. After stimulated for 12 hours, the TNAP expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.44±0.08), (0.52±0.14), (0.84±0.16) and (0.55±0.10) respectively ( F=290.96, P<0.001). After stimulated for 3 days, the OPN expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.61±0.84), (0.95±0.16), (1.65±0.24) and (0.99±0.10) respectively ( F=507.72, P<0.001). After stimulated for 12 hours, the BMP-2 expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.77±0.05), (1.69±0.16), (2.81±0.26) and (0.57±0.12) respectively ( F=959.09, P<0.001). After stimulated for 3 days, the Runx2 expression in blank control, IL-6 group, IL-6+sIL-6R group,IL-6+sIL-6R+sgp130 group were (0.57±0.03) , (0.92±0.10), (1.31±0.13) and (0.66±0.06) respectively ( F=1141.27, P<0.001). Comparing with Jurkat cells (positive control) and CEM cells (negative control), HUASMCs limited expressed mIL-6R. Conclusion:IL-6 may induce HUASMCs osteogenic differentiation and calcification mainly via the sIL-6R-mediated trans-signaling pathway.

Objective:To determine the median effective dose (ED 50) and the 95% effective dose (ED 95) of remifentanil inhibiting responses to endotracheal intubation without neuromuscular relaxant when combined with dexmedetomidine in patients undergoing thyroid surgery. Methods:American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, with body mass index of 18-28 kg/m 2, scheduled for elective thyroid surgery under intraoperative neuromonitoring, were enrolled in this study.Dexmedetomidine was intravenously injected in a loading dose of 0.8 μg/kg at 10 min before anesthesia induction.Anesthesia was induced by intravenously injecting midazolam 0.1 mg/kg, etomidate 0.4 mg/kg and the preset dose of remifentanil.The dose of remifentanil was determined using up-and-down sequential method.The initial dose was set at 3.7 μg/kg.The dose of remifentanil in the next case was determined according to whether responses to endotracheal intubation occurred, and the ratio between the two successive doses was 1.1.The ED 50, ED 95 and 95% confidence interval (CI) were calculated by Probit analysis. Results:when combined with dexmedetomidine for anesthesia induction, the ED 50 (95% CI) of remifentanil inhibiting responses to endotracheal intubation without neuromuscular relaxant was 3.39 (3.29-3.50) μg/kg, and the ED 95 (95% CI) was 3.52 (3.48-3.64) μg/kg. Conclusion:when combined with dexmedetomidine, the ED 50 of remifentanil inhibiting responses to endotracheal intubation without neuromuscular relaxant is 3.39 μg/kg, and the ED 95 is 3.52 μg/kg.

【Objective】 To study the fairness of blood bank resources allocation in China, aimed at providing references for reasonable allocation of blood bank resources. 【Methods】 A questionnaire survey was conducted among 32 provincial blood centers and 321 regional central blood banks across China in August 1~25, 2018. Resource allocation of blood banks in China was analyzed using descriptive methods, and the fairness of resource allocation were analyzed using Lorenz curve, Gini coefficient and Theil index. 【Results】 Blood bank resources and services showed an overall upward trend from 2013 to 2017. The fairness of institutional coverage was optimal in 2017 according to the Lorenz curve and Gini coefficient, suggesting the allocation of blood bank resources according to the population was better than geographic area. The fairness of health technicians staffing was the worst from the perspective of geographic area. The total Theil index was 0.448 5~0.526 7, and the differences was contributed more by intra group comparison than that of inter group. 【Conclusion】 The unbalanced development underlying in the provincial and regional blood centers has been observed, and the service capacity needs to be further improved. The resource allocation varies greatly among regions, and it is recommended to optimize the regional planning of blood bank resources.

Objective To investigate the correlation between the severity of alcoholic fatty liver disease and the amount of fat in the abdominal cavity and the serum inflammatory factor IL-18 and IL-8. Methods From October 2016 to October 2017,one hundred and twenty patients with AFLD in the First Hospital of Hebei Medical University were divided into light,medium,heavy groups according to the severity of fatty lesions by color Doppler Ultrasound. There were 40 mild patients,50 moderate patients and 30 severe patients. Forty healthy subjects were selected as controls. All the participants underwent CT scanning. The intra-abdominal fat area (VAT),abdominal subcutaneous fat area (SAT) and total abdominal fat area (TA) were measured. The liver function was measured by biochemical analyzer and enzyme-linked immunoassay (ELISA). (ELSIA) IL-18 was detected and IL-8 was detected by radioimmunoassay. Results The VAT of the healthy control group and the mild,medium and severe AFLD group were (70. 28±10. 19),(114. 38 ± 9. 97),(146. 73±10. 19),(163. 38±12. 69) cm2. The TA of the healthy control group and the mild, medium and severe AFLD group were ( 256. 72± 34. 56),( 332. 19 ± 33. 28),( 387. 49± 32. 28),( 478. 19 ±31. 02) cm2. The SAT of the healthy control group and the light,medium and severe AFLD group were (156. 23±28. 19),(203. 43±27. 12),(246. 19±26. 89),(271. 19 ±27. 94) cm2,respectively. Aspartate aminotransferase (AST) of the healthy control group and the mild,medium and severe AFLD group were (18. 50±1. 12),(23. 50±1. 21),(25. 50±1. 24),(29. 50± 1. 43) U/L. Alanine aminotransferase (ALT) of the healthy control group and the light, medium and severe AFLD group were ( 18. 50 ± 2. 14), ( 26. 50 ±2. 22),(35. 50±2. 34),(38. 50±2. 11) U/L. γ-glutamyltransferaseof the healthy control group and the light,medium and severe AFLD group were ( 16. 50 ± 2. 11), ( 32. 50 ± 2. 23), ( 47. 50 ± 2. 31), ( 48. 00 ±2. 43) U/L,respectively. Compared with the healthy control group,VAT,TA,SAT,AST,ALT andγ-GT in the light,medium and heavy AFLD group showed statistically significant differences ( P＜0. 05) . Compared with the mild AFLD group, VAT, TA, SAT, AST, ALT and γ-GT in the medium and heavy AFLD group showed statistically significant differences ( P＜0. 05) . Compared with the moderate AFLD group,the VAT, TA,SAT, AST, ALT, and γ-GT of the severe AFLD group showed statistically significant differences ( P＜0. 05). The data of the three AFLD groups showed that the concentration of all indicators were increasing as the severity of fat deepened. IL-18 of the healthy control group and the light,medium and severe AFLD group were (45. 67±4. 51),(52. 18±5. 09),(59. 87±4. 98),(64. 18±5. 12) ng/L; IL-8 of the healthy control group and the light, medium and severe AFLD group were ( 78. 92 ± 5. 07), ( 115. 62 ± 4. 89), ( 223. 76 ± 6. 78),(286. 42±7. 02) g/L. Compared with every group,IL-18 and IL-8 of light,medium and severe AFLD group showed statistically significant differences (F＝1035. 67,2. 93×105,P＜0. 001); compared with mild AFLD group,IL-18 and IL-8 of medium and heavy group showed statistically significant differences;compared with moderate AFLD group,IL-18 and IL-8 of severe group AFLD showed statistically significant differences ( P＜0. 001) . The levels of inflammatory factors IL-18 and IL-8 increased with the severity of steatosis. The severity of AFLD was significantly positively correlated with VAT,TA,SAT,IL-18 and IL-8 ( r 0. 415(P＜0. 001), 0. 435 ( P＜0. 001), 0. 512 ( P＜0. 001), 0. 274 ( P＜0. 001 ), 0. 689 ( P ＜0. 001). Conclusion Fat control is an important measure to prevent AFLD. IL-18 and IL-8 can reflect the severity of liver injury in AFLD and have important significance in judging prognosis.