AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objective:To explore the clinical risk factors and pregnancy outcomes in women with hyperglycemia in pregnancy (HIP) complicated with hypertensive disorders of pregnancy (HDP).Methods:This retrospective cohort study included 43 973 singleton live births delivered at the Obstetrics and Gynecology Hospital of Fudan University between September 2017 and December 2022. Participants were categorized into four groups: HH group (HIP with HDP, n=1 011), HIP group ( n=5 469), HDP group ( n=3 486), and control group ( n=34 007). Baseline characteristics and perinatal outcomes were compared using the Chi-square test (or Fisher's exact test). Logistic regression identified risk factors and adverse outcome risks and analyze the impact of HH on neonatal weight. Results:HH accounted for 15.6% (1 011/6 480) of HIP cases, with an overall incidence of 2.3% (1 011/43 973). HIP and HDP were strongly correlated [ OR=1.803, 95% CI: 1.672-1.945]. Advanced maternal age (≥35 years at estimated due date), primiparity, and pre-pregnancy overweight/obesity (body mass index ≥24 kg/m2) were independent risk factors for HH [ OR (95% CI): 1.305 (1.113-1.529), 1.845 (1.545-2.203), and 2.316 (1.981-2.718), respectively]. Compared to the HIP group, the HH group had significantly higher risks of preterm birth [10.3% (104/1 011) vs. 6.3% (344/5 469), OR=1.627 (95% CI:1.280-2.068)], cesarean delivery [57.0% (576/1 011) vs. 41.9% (2 289/5 469), OR=1.701 (95% CI:1.474-1.963)], and neonatal birth weight < P10 [13.9% (141/1 011) vs. 9.0% (494/5 469), OR=1.668 (95% CI:1.336-2.083)]. Stratified analysis revealed a 73.4% increased risk of birth weight < P10 in the gestational diabetes mellitus A1 with HDP subgroup ( aOR=1.734, 95% CI: 1.416-2.125). Conclusions:Advanced age, pre-pregnancy overweight/obesity, and primiparity are risk factors for HH. Compared to isolated HIP, HH is associated with elevated risks of preterm birth, cesarean delivery, and abnormal neonatal birth weight, though the impact on birth weight may vary by HIP subtype.

AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

Objective:To explore the clinical risk factors and pregnancy outcomes in women with hyperglycemia in pregnancy (HIP) complicated with hypertensive disorders of pregnancy (HDP).Methods:This retrospective cohort study included 43 973 singleton live births delivered at the Obstetrics and Gynecology Hospital of Fudan University between September 2017 and December 2022. Participants were categorized into four groups: HH group (HIP with HDP, n=1 011), HIP group ( n=5 469), HDP group ( n=3 486), and control group ( n=34 007). Baseline characteristics and perinatal outcomes were compared using the Chi-square test (or Fisher's exact test). Logistic regression identified risk factors and adverse outcome risks and analyze the impact of HH on neonatal weight. Results:HH accounted for 15.6% (1 011/6 480) of HIP cases, with an overall incidence of 2.3% (1 011/43 973). HIP and HDP were strongly correlated [ OR=1.803, 95% CI: 1.672-1.945]. Advanced maternal age (≥35 years at estimated due date), primiparity, and pre-pregnancy overweight/obesity (body mass index ≥24 kg/m2) were independent risk factors for HH [ OR (95% CI): 1.305 (1.113-1.529), 1.845 (1.545-2.203), and 2.316 (1.981-2.718), respectively]. Compared to the HIP group, the HH group had significantly higher risks of preterm birth [10.3% (104/1 011) vs. 6.3% (344/5 469), OR=1.627 (95% CI:1.280-2.068)], cesarean delivery [57.0% (576/1 011) vs. 41.9% (2 289/5 469), OR=1.701 (95% CI:1.474-1.963)], and neonatal birth weight < P10 [13.9% (141/1 011) vs. 9.0% (494/5 469), OR=1.668 (95% CI:1.336-2.083)]. Stratified analysis revealed a 73.4% increased risk of birth weight < P10 in the gestational diabetes mellitus A1 with HDP subgroup ( aOR=1.734, 95% CI: 1.416-2.125). Conclusions:Advanced age, pre-pregnancy overweight/obesity, and primiparity are risk factors for HH. Compared to isolated HIP, HH is associated with elevated risks of preterm birth, cesarean delivery, and abnormal neonatal birth weight, though the impact on birth weight may vary by HIP subtype.

To investigate the short-term effectiveness and safety of sublingual allergen immunotherapy with allergen sprays (SLIT-sprays) in Chinese patients with allergic rhinitis (AR) with or without asthma using real-world data. The retrospective cohort study included 100 patients who received SLIT-sprays in the ENT departments in Hainan Shulan (Boao) Hospital and Boao Super Hospital between October 2023 and August 2024. A questionnaire survey was conducted to collect clinical data on the effectiveness and safety of SLIT-sprays, examining the types and incidence of adverse events (AEs) during treatment, treatments after the occurrence of AEs, and changes in Visual Analog Scale (VAS) scores before and after SLIT-sprays. Self-reports from 100 patients were collected. The results showed that the average treatment duration for the 100 patients was (90.7±58.9) days, median 78.5 days. Using changes in VAS scores as the effectiveness assessment, the average VAS score increased by 4.2 (95% CI: 4.06-4.34). The incidence of AEs during the SLIT-sprays was 17.0% (17/100), all of which were mild to moderate local reactions, with no serious AEs reported. There were no significant differences in AE incidence among patients with different diseases (AR or AR with asthma and asthma alone) (χ 2=1.831, P>0.05), different age group (χ 2=1.477, P>0.05), different types of allergen extracts (χ 2=1.613, P>0.05), or the number of allergen extracts used (patients using one or two allergen extracts) (Fisher′s exact test, P>0.05). In conclusion, Chinese patients showed good safety and tolerability to SLIT-sprays, with all AEs being mild to moderate local reactions and no serious or systemic AEs occurring. Patients reported positive subjective evaluations of the early treatment effects.