Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

The key to the onset and progression of the functional impairments of orthopedic diseases is imba-lance of deficiency and excess， disharmony of movement and stillness， dislocation of sinews and bones， imbalance of rigidity and flexibility， and disharmony of body and spirit. Based on this， the "five views" treatment principle has been proposed for traditional Chinese medicine （TCM） orthopedic rehabilitation， which include the view of balancing deficiency and excess， combining movement and stillness， focusing on both sinews and bones， integrating rigidity and flexibility， and harmonizing body and spirit. Correspondingly， the "five views" collaborative rehabilitation clinical model is established， providing a reference for enhancing the systematization and targeting of TCM orthopedic rehabilitation.

Objective To construct the core outcome set(COS)for clinical research on Uyghur medicine in treating psoriasis by using internationally-recognized research methods,thus to aid the researchers in choosing the standardized outcomes and to enhance the quality of evidence from research findings.Methods A systematic retrieval of Chinese and English databases was conducted to collect outcomes from clinical studies,systematic reviews,and registered protocols of Uyghur medicine for treating psoriasis.An outcome pool was constructed based on the results of literature review.The outcomes were supplemented after qualitative surveys of patients and physicians,and then an initial list of outcomes was formed.Two rounds of Delphi surveys on the initial list were conducted for obtaining Likert scale ratings from different stakeholder groups to evaluate the importance of outcomes.After that,a consensus meeting was held to finalize the COS for clinical research on Uyghur medicine in treating psoriasis.Results The COS for clinical research on Uyghur medicine in treating psoriasis comprises six domains,totaling 14 outcomes.The 14 outcomes were psoriasis symptoms(psoriasis area and area severity index),skin manifestations(erythema,scaling,infiltration,etc.),investigator global assessment,patient global assessment,treatment satisfaction,health-related quality of life,recurrence rate,adverse events,drug adverse reactions,blood routine,urine routine,liver and kidney function,Uyghur medicine symptom assessment,and fluid changes.Conclusion The COS for clinical research on Uyghur medicine in treating psoriasis has been constructed,and will provide a reference for the selection of efficacy-evaluation outcomes and for the reporting of outcomes in related studies.

ObjectiveTo investigate the general situation， dietary factors， and clinical features of patients with recurrent primary common bile duct stones， and to provide a basis for effective prevention of stone recurrence. MethodsA retrospective analysis was performed for 23 730 patients who underwent cholecystectomy due to cholelithiasis in Department of Hepatobiliary， Pancreatic and Spleen Surgery， Inner Mongolia People’s Hospital， from January 2013 to December 2023， and according to the presence or absence of recurrence of primary common bile duct stones after surgery， 334 patients were divided into recurrence group. The recurrence group was further analyzed based on sex in terms of recurrence rate， recurrence cycle， recurrence age， recurrence type， and general， disease， imaging， and dietary factors. The independent-samples t test was used for comparison of continuous data between two groups， the chi-square test was used for comparison of categorical data between two groups. ResultsThere were 334 cases of recurrence of primary bile duct stones after cholecystectomy， with a recurrence rate of 1.41%， and the highest frequency of recurrence cycle was observed in 10 years after surgery， with a significant difference in recurrence cycle between the male and female patients （t=5.238， P<0.001）. There was a significant difference in the recurrence rate of stones after surgery between the patients with simple gallstones and those with gallbladder and common bile duct stones at initial diagnosis （1.23% vs 2.76%， χ²=42.104， P<0.001）. The patients with recurrence aged >60 years accounted for the highest proportion in the whole population and in both male and female populations， and 92% were Han residents； 10% of the patients with recurrence had a family history of gallstones， and as for comorbidities， the patients with hypertension accounted for the highest proportion. Among the patients with recurrence， the patients with smoking or drinking accounted for 76.7% and 10.3%， respectively. As for body weight， 63.8% of the patients with recurrence had a normal body mass index （BMI）， and 23.2% of the patients were overweight； compared with body weight at the time of the first gallbladder surgery， a reduction in body weight was observed in 60.1% of the patients with recurrence， while an increase in body weight was observed in 22.9% of the patients with recurrence. There were significant differences between the male and female patients with recurrence in age composition， ethnicity， the type of place of residence， comorbidities， smoking， drinking， BMI， and the change in body weight （all P<0.001）. As for the type of stone recurrence， the ratio of multiple stones， solitary stones， and muddy stones was 74∶15∶11， and the stone size of <1 cm， 1-2 cm， and >2 cm accounted for about 40.5%， 48.8%， and 10.6%， respectively. As for the surgical procedure， the patients undergoing laparotomy accounted for 66.1%， and those undergoing laparoscopy accounted for 33.9%. The patients with various types of dyslipidemia accounted for a percentage of<30%. There were significant differences between the male and female patients with recurrence in the type of stones at initial onset， the type and size of stones， and surgical procedure （all P<0.001）. Imaging data showed that 4 patients had an abnormal structure of the bile duct， manifesting as long and curve cystic ducts， and 73.1% of the patients had common bile duct dilatation after surgery. The follow-up of dietary factors showed irregular diets in 55.8% of the patients with recurrence. As for the dietary structure， meat and staple food accounted for 43.8% and 37.8%， respectively， which showed a sex difference， with meat in male patients and staple food in female patients； 64.1% of the patients with recurrence had a high-salt and high-oil diet； 59.8% of the patients had changes in diet after the first surgery for stones， among whom 80% were able to have a regular diet， and the patients with a regular diet accounted for 92%. ConclusionThere is a relatively low recurrence rate of primary common bile duct stones in this area， and there is no sex difference. The peak of recurrence is 10 years after surgery， and recurrence of stones is mainly observed in the population aged >60 years. The analysis of dietary and clinical features can help doctors and patients to further understand the characteristics of the recurrence of primary common bile duct stones and provide a basis for subsequent targeted prevention.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objectives:This study aims to explore the causal relationships between immune cells and serum metabolites in the development of coronary heart disease(CHD)using Mendelian randomization(MR)methods.Methods:We conducted a two-sample MR analysis utilizing data from the FinnGen Project's genome-wide association study(GWAS)on CHD,alongside data on metabolites and immune cells from the GWAS catalog.For the identified associated metabolites,we further employed mediation MR methods to evaluate their mediating roles in the influence of immune cells on CHD.Results:The MR analysis indicated that three immune cells(IgD-CD24-%B cell,CD11b on CD14+monocyte,HLA DR on DC)had stable causal relationship with CHD(under the premise of inverse variance weighted[IVW]method P<0.05,both MR-Egger and weighted median methods also showed P<0.05).Furthermore,these immune cells were associated with CHD through four metabolites(N-acetylneuraminic acid levels,the ratio of desmethyltaurine to taurine,X-24801 and X-18779).Conclusions:This study reveals the causal relationships between immune cells and serum metabolites in the pathogenesis of CHD,providing new biomarkers for early prediction and risk assessment of CHD.

Objective:To explore the influencing factors of absorption effect postoperative ablation area after microwave ablation(MWA)for papillary thyroid microcarcinoma(PTMC).Methods:The clinical and ultrasound data of 101 patients with single PTMC who underwent microwave ablation in Beijing Friendship Hospital between April 2019 and July 2023 were collected.According to the endpoint event of whether the ablation area disappeared one year after MWA,they were divided into disappearance group(52 cases)and non-disappearance group(49 cases).Univariate and multivariate logistic regression were used to analyze the factors of affecting the absorption effect of ablation area,and a regression model was constructed.Receiver operating characteristic(ROC)curve was drawn to test the predictive efficacy of the model.Results:There were significant differences in the age,coarse calcification in the nodule,ablation time,Hashimoto's thyroiditis between two groups(x2=4.708,12.180,19.497,8.457,P<0.05),respectively.There were also significant differences in maximum diameter of nodule,nodule volume,ablation energy between two groups(Z=-3.929,-3.969,-3.677,P<0.05).Multivariate logistic regression analysis showed that age≥50 years old,coarse calcification in the nodule,ablation time≥50s,and Hashimoto's thyroiditis were independent influencing factors for the non-disappearance of ablation area one year after MWA for PTMC(OR=4.464,3.733,10.063,4.173,P<0.05).The ROC curve analysis showed that the area under curve(AUC)of the regression model in predicting non-disappearance of ablation area after MWA for PTMC was 0.853(95%CI:0.777-0.929),and the diagnostic sensitivity and specificity of that were respectively 75.5%and 82.7%.Conclusion:The logistic regression model,that is constructed on the basis of clinical information,preoperative ultrasound features,and thermal ablation parameters,has high clinical application value in predicting the postoperative absorption of the ablation area in patients who undergo MWA for PTMC.

OBJECTIVE To explore the effect of Zi Zhu Ointment combined with herbal fumigation on wound heal-ing,oxidative stress and microribonucleic acid(miR)-200b of the patients with diabetic foot infection.METHODS A total of 102 patients with diabetic foot infection who were treated in Heping Hospital Affiliated to Changzhi Medical College from Sep.2020 to Sep.2023 were enrolled in the study and were divided into the control group with 48 cases and the study group with 54 cases according to the treatment program.The control group was trea-ted with conventional therapy and herbal fumigation,the study group was given additional Zi Zhu Ointment on ba-sis of the treatment of the control group,and both groups were persistently treated for 1 month.The clinical cura-tive effect,wound healing status,hemodynamics indexes of dorsal foot,pain score,oxidative stress indexes and miR-200b expression levels were observed and compared between the two groups of patients.RESULTS The effec-tive rate of clinical treatment of the study group was higher than that of the control group after the treatment(Z=2.138,P=0.033).The wound area of the study group was(0.42±0.05)cm2 after the treatment,smaller than that of the control group;the cover area of neoplastic granulation tissue of the study group was(16.87±3.21)cm2,larger than that of the control group;the coverage fraction of the neoplastic granulation tissue of the study group was(55.23±6.17)％,greater than that of the control group;there were significant differences between the two groups(P＜0.05).The blood vessel diameter of dorsal foot of the study group was greater than that of the control group after the treatment,the blood flow velocity of the study group was greater than that of the control group,and the visual analogue scale(VAS)score of the study group was lower than that of the control group(P＜0.05).There were no significant differences in the expression levels of advanced oxidative protein product(AOPP),superoxide dismutase(SOD),malondialdehyde(MDA)and miR-200b between the two groups of pa-tients before the treatment;the expression levels of AOPP,MDA and miR-200b of the study group were lower than those of the control group after the treatment,while the SOD level of the study group was higher than that of the control group(P＜0.05).CONCLUSIONS Zi Zhu Ointment combined with herbal fumigation can remarkably improve the clinical curative effect on the patients with diabetic foot infection,promote the wound healing,im-prove the arterial hemodynamics of dorsal foot,and relieve the pain.The mechanism may be associated with the improvement of oxidative stress response and downregulated expression level of miR-200b.