AIM To investigate the clinical effects of Modified Banxia Xiexin Decoction combined with Lizhong Decoction on patients with type 2 diabetes mellitus due to Cold-heat Complex in the Middle Energizer.METHODS One hundred and sixty-eight patients were randomly assigned into control group(84 cases)for 12-week intervention of conventional treatment,and observation group(84 cases)for 12-week intervention of Modified Banxia Xiexin Decoction,Lizhong Decoction and conventional treatment.The changes in clinical effects,compliance rate of blood glucoses,discontinuation and reduction rate of hypoglycemic drugs,continuous glucose parameters(TIR,GVP,FPG-ARV,MAGE),FPG,2 hPG,HbA1c,FINS,HOMA-β,HOMA-IR,lnISI,intestinal flora metabolites(SCFAs,CA,DC A,CDCA,CA/CDCA),score for Cold-heat Complex in the Middle Energizer and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher marked improvement rate,total effective rate,compliance rate of blood glucoses and discontinuation and reduction rate of hypoglycemic drugs,than the control group(P＜0.05).After the treatment,the two groups displayed increased TIR,FINS,HOMA-β,lnISI,SCFAs,CDCA(P＜0.05),and decreased GVP,FPG-ARV,MAGE,FPG,2 hPG,HbA1c,HOMA-IR,CA,DC A,CA/CDCA,score for Cold-heat Complex in the Middle Energizer(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with type 2 diabetes mellitus due to Cold-heat Complex in the Middle Energizer,Modified Banxia Xiexin Decoction combined with Lizhong Decoction can improve islet β cell function and insulin resistance,enhance insulin sensitivity index and compliance rate of blood glucoses,reduce blood glucose fluctuation and dosages of hypoglycemic drugs,regulate intestinal flora metabolites,and affect glucose metabolism.

Objective To observe the clinical efficacy and safety of adalimumab(AD A)injection combined with methotrexate(MTX)tablets in the treatment of patients with rheumatoid arthritis(RA),and the effects of joint function,serum rheumatoid factor(RF),anti-citrullinated peptide(CCP)antibody and tumor necrosis factor-α(TNF-α).Methods The RA patients were divided into control group and treatment group according to cohort method.All patients were given intra-articular injection of prednisolone acetate injection at initial dose of 5 mg every time,once every week for 4 weeks,and then adjusted dose every 2 weeks according to the disease conditions.On this basis,the control group received oral MTX tablets 10 mg once a week,and the treatment group was combined with subcutaneous injection of ADA injection 40 mg twice a week.Both groups were treated continuously for 3 months.The clinical efficacy,clinical characteristics(swollen joint count,tender joint count,morning stiffness time),joint function[disease activity scale(DAS)-28 score,joint pain degree score],serum RF,anti-CCP antibody and TNF-α levels before and after treatment were compared between the two groups.Results The treatment group and control group included 52 and 45 cases,respectively.After treatment,the total effective rates of treatment group and control group were 92.31％(48 cases/52 cases)and 75.56％(34 cases/45 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the swollen joint counts in treatment group and control group were 4.31±1.08 and 5.56±1.25;the tender joint counts were 6.19±1.68 and 7.92±1.43;the morning stiffness times were(44.47±11.06)and(58.63±12.46)min;the DAS28 scores were(2.67±0.73)and(3.35±0.86)points;the joint pain scores were(2.47±0.76)and(3.29±0.85)points;serum RF levels were(80.25±24.31)and(114.46±27.63)U·mL-1;serum anti-CCP antibody levels were(7.41±1.48)and(9.90±1.72)RU·mL-1;the levels of serum TNF-α were(24.16±6.33)and(34.92±7.98)pg·mL-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.001).The adverse drug reactions in the treatment group mainly included loss of appetite,headache and erythema at the injection site.The adverse drug reactions in the control group included loss of appetite and nausea and vomiting.The total incidences of adverse drug reactions in the treatment group and the control group were 5.77％and 4.44％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The treatment of RA with ADA injection combined with MTX tablets is more effective than using MTX tablets alone,and the former one can more significantly improve joint function and reduce levels of inflammatory markers,and without increasing the incidences of adverse drug reactions.

Programmed cell death plays an important role in the growth and development of organ-ism and homeostasis of tissues and organs.Necroptosis,a new mode of programmed cell death,characterized by necrosis in morphology,can cause cell breakdown and release of a significant num-ber of damage-associated molecular patterns,which play an important role in the occurrence and development of diseases.Viral infection is a serious health risk to both humans and domestic ani-mals.Research has confirmed that necroptosis functions as a cell death pathway in viral infections.In this paper,we review the current research advances on necroptosis related to viral infections,e-lucidate the molecular mechanism of mutual regulation between viral infection and necroptosis,and discuss the progress in the application of necroptosis inhibitors,to provide new ideas for the pre-vention and treatment of viral infections.

Objective:To explore the value of contrast enhanced ultrasonography(CEUS) combined with shear wave elastography (SWE) in the diagnosis of urethral stricture.Methods:One hundred and twenty patients with urethral stricture were recruited, and preoperative retrograde urography, common urethral ultrasound, and CEUS were used to measure the length of the stricture site, and SWE was used to detect the elasticity value of the stricture site and its nearby spongiosum. Intraoperative urethral stricture lesion site measurements were performed to confirm the actual lesion location and length during surgery and to compare them with the lengths measured in the preoperative examination;4 months after surgery, SWE was used to detect the stiffness of the surgical site and to assess the surgical efficacy and prognosis.Results:The stenosis length measured by CEUS and intraoperative measurement had no statistical difference: (4.41 ± 1.47) cm vs. (4.37 ± 1.36) cm, t = 0.22, P>0.05. The elastic value in urethra stenosis in SWE was higher than that in normal urethra: (33.1 ± 6.7) kPa vs. (23.3 ± 4.1) kPa, there was statistical difference ( t = 13.67, P<0.05). The elastic value of unobstructed urethra and that of normal urethra after reconstruction had no statistical difference ( t = 0.95, P>0.05). Conclusions:CEUS combined with SWE is a safe, accurate and effective method to evaluate urethral stricture. SWE can be used to measure postoperative outcomes and recurrence.

Objective To investigate the effect of local histopathological changes of thyroid nodules after ultrasound-guided fine needle aspiration biopsy(US-FNBA)on laparoscopic thyroid surgery.Methods The clinical data of 120 patients with thyroid malignant tumors admitted to Xiaogan Hospital of Wuhan University of Science and Technology from January 2020 to December 2022 were retrospectively analyzed,and according to whether received US-FNAB before surgery they were divided into the observation group(with US-FNAB)and the control group(without US-FNAB),with 60 cases in each group.The operation time,change of parathyroid hormone(ΔPTH)before and after surgery,change of serum Ca2+concentration(serum ΔCa2+)before and after surgery,drainage volume 24 hours after surgery and incidence of complications were compared between the two groups.According to fine needle aspiration-to-surgery(FTS),the patients in the observation group were further divided into the group A(FTS≤3 days)and the group B(FTS>3 days),and the effect of US-FNAB on laparoscopic thyroid surgery was explored combined with the pathological changes of the thyroid puncture capsule of the two groups.Results The operation time of the observation group was longer than that of the control group(P<0.05),and there was no significant difference in the drainage volume 24 hours after surgery,ΔPTH,serum ΔCa2+,or proportions of facial or limb numbness,hypoparathyroidism,recurrent laryngeal nerve integrity,and hypocalcemia between the two groups(P>0.05).There was no significant difference in the operation time,ΔPTH,serum ΔCa2+,drainage volume 24 hours after surgery,hypocalcemia,recurrent laryngeal nerve integrity or hypothyroidism between the group A and group B(P>0.05).The proportion of patients with facial or limb numbness after surgery in the group A was significantly lower than that in the group B(P<0.05).Conclusion Preoperative US-FNAB for thyroid nodules may prolong the operation time in patients undergoing laparoscopic thyroid surgery,and surgical treatment in early aspiration can help decrease this effect and reduce the incidences of postoperative hypocalcemia and hypothyroidism.

Objective To observe the clinical efficacy and safety of adalimumab(AD A)injection combined with methotrexate(MTX)tablets in the treatment of patients with rheumatoid arthritis(RA),and the effects of joint function,serum rheumatoid factor(RF),anti-citrullinated peptide(CCP)antibody and tumor necrosis factor-α(TNF-α).Methods The RA patients were divided into control group and treatment group according to cohort method.All patients were given intra-articular injection of prednisolone acetate injection at initial dose of 5 mg every time,once every week for 4 weeks,and then adjusted dose every 2 weeks according to the disease conditions.On this basis,the control group received oral MTX tablets 10 mg once a week,and the treatment group was combined with subcutaneous injection of ADA injection 40 mg twice a week.Both groups were treated continuously for 3 months.The clinical efficacy,clinical characteristics(swollen joint count,tender joint count,morning stiffness time),joint function[disease activity scale(DAS)-28 score,joint pain degree score],serum RF,anti-CCP antibody and TNF-α levels before and after treatment were compared between the two groups.Results The treatment group and control group included 52 and 45 cases,respectively.After treatment,the total effective rates of treatment group and control group were 92.31％(48 cases/52 cases)and 75.56％(34 cases/45 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the swollen joint counts in treatment group and control group were 4.31±1.08 and 5.56±1.25;the tender joint counts were 6.19±1.68 and 7.92±1.43;the morning stiffness times were(44.47±11.06)and(58.63±12.46)min;the DAS28 scores were(2.67±0.73)and(3.35±0.86)points;the joint pain scores were(2.47±0.76)and(3.29±0.85)points;serum RF levels were(80.25±24.31)and(114.46±27.63)U·mL-1;serum anti-CCP antibody levels were(7.41±1.48)and(9.90±1.72)RU·mL-1;the levels of serum TNF-α were(24.16±6.33)and(34.92±7.98)pg·mL-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.001).The adverse drug reactions in the treatment group mainly included loss of appetite,headache and erythema at the injection site.The adverse drug reactions in the control group included loss of appetite and nausea and vomiting.The total incidences of adverse drug reactions in the treatment group and the control group were 5.77％and 4.44％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The treatment of RA with ADA injection combined with MTX tablets is more effective than using MTX tablets alone,and the former one can more significantly improve joint function and reduce levels of inflammatory markers,and without increasing the incidences of adverse drug reactions.

Programmed cell death plays an important role in the growth and development of organ-ism and homeostasis of tissues and organs.Necroptosis,a new mode of programmed cell death,characterized by necrosis in morphology,can cause cell breakdown and release of a significant num-ber of damage-associated molecular patterns,which play an important role in the occurrence and development of diseases.Viral infection is a serious health risk to both humans and domestic ani-mals.Research has confirmed that necroptosis functions as a cell death pathway in viral infections.In this paper,we review the current research advances on necroptosis related to viral infections,e-lucidate the molecular mechanism of mutual regulation between viral infection and necroptosis,and discuss the progress in the application of necroptosis inhibitors,to provide new ideas for the pre-vention and treatment of viral infections.

Objective To investigate the effect of local histopathological changes of thyroid nodules after ultrasound-guided fine needle aspiration biopsy(US-FNBA)on laparoscopic thyroid surgery.Methods The clinical data of 120 patients with thyroid malignant tumors admitted to Xiaogan Hospital of Wuhan University of Science and Technology from January 2020 to December 2022 were retrospectively analyzed,and according to whether received US-FNAB before surgery they were divided into the observation group(with US-FNAB)and the control group(without US-FNAB),with 60 cases in each group.The operation time,change of parathyroid hormone(ΔPTH)before and after surgery,change of serum Ca2+concentration(serum ΔCa2+)before and after surgery,drainage volume 24 hours after surgery and incidence of complications were compared between the two groups.According to fine needle aspiration-to-surgery(FTS),the patients in the observation group were further divided into the group A(FTS≤3 days)and the group B(FTS>3 days),and the effect of US-FNAB on laparoscopic thyroid surgery was explored combined with the pathological changes of the thyroid puncture capsule of the two groups.Results The operation time of the observation group was longer than that of the control group(P<0.05),and there was no significant difference in the drainage volume 24 hours after surgery,ΔPTH,serum ΔCa2+,or proportions of facial or limb numbness,hypoparathyroidism,recurrent laryngeal nerve integrity,and hypocalcemia between the two groups(P>0.05).There was no significant difference in the operation time,ΔPTH,serum ΔCa2+,drainage volume 24 hours after surgery,hypocalcemia,recurrent laryngeal nerve integrity or hypothyroidism between the group A and group B(P>0.05).The proportion of patients with facial or limb numbness after surgery in the group A was significantly lower than that in the group B(P<0.05).Conclusion Preoperative US-FNAB for thyroid nodules may prolong the operation time in patients undergoing laparoscopic thyroid surgery,and surgical treatment in early aspiration can help decrease this effect and reduce the incidences of postoperative hypocalcemia and hypothyroidism.

Objective:To explore the mechanisms of action of Huanglian Jiedu decoction combined with Xijiao Dihuang decoction (HLJDT-XJDH) in regulating fibroblasts in the treatment of psoriasis. Methods:A mouse model of psoriasis was established by topical application of imiquimod 5% cream on the shaved back; HLJDT-XJDH at different doses of 7.7 and 30.6 g/kg was administered via gavage for intervention, and methotrexate (2 mg/kg) served as a positive control; after 7 days, the severity of skin lesions was assessed using the psoriasis area and severity index (PASI), while histopathological changes of skin tissues were evaluated using hematoxylin-eosin (HE) staining and Baker scoring. For in vitro experiments, fibroblasts were divided into a control group, a model group, a low-dose (5% drug-containing serum) intervention group, and a high-dose (20% drug-containing serum) intervention group; cells in the control group were cultured with 20% normal rat serum for 24 hours; in the model group, cells cultured with 20% normal rat serum were stimulated with 5 ng/ml tumor necrosis factor (TNF) -α and 50 ng/ml interleukin (IL) -17A for 24 hours to mimic fibroblasts during the occurrence of psoriasis; cells in the low- and high-dose intervention groups received the same stimulation as the model group, and were cultured for 24 hours with 5% and 20% HLJDT-XJDH-containing serum, respectively, but not with the 20% normal rat serum. After the above treatment, these cells were co-cultured with keratinocytes (HaCaT cells) using a Transwell system. In addition, on the basis of the control group, fibroblasts were divided into the model group, 20% drug-containing serum intervention group, and 20% drug-containing serum intervention + OE-SFRP2 group; TNF-α and IL-17A were used to stimulate the cells to simulate the psoriatic state; the treatment in the 20% drug-containing serum intervention group was carried out as previously described; in the 20% drug-containing serum intervention + OE-SFRP2 group, cells were transfected with the vector for 48 hours to establish an overexpression model, followed by culture with 20% drug-containing serum for 24 hours, without co-culture with HaCaT cells.. Cell counting kit-8 (CCK-8) assay was performed to assess cell viability, flow cytometry to measure apoptosis rates, enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as chemokine ligand (CXCL) 1 and CXCL12 in mouse serum or cell culture supernatant, qPCR to determine the mRNA expression of inflammatory cytokines, chemokines, cell cycle- and proliferation-related factors, as well as SFRP2 in mouse skin tissues or cells, and Western blot analysis to determine the protein expression of SFRP2, Wnt3a, and β-catenin in fibroblasts. One-way analysis of variance was employed for intergroup comparisons, and post-hoc analysis was conducted using Tukey's test. Results:In vivo mouse experiments showed that compared with the normal control group, the model group exhibited typical psoriatic characteristics in skin morphology, including significant inflammatory infiltration in skin tissues and marked epidermal thickening; compared with the normal control group, the serum levels of TNF-α (531.16 ± 28.27 pg/ml vs. 239.58 ± 10.39 pg/ml), IL-1β (111.40 ± 5.16 pg/ml vs. 80.35 ± 3.87 pg/ml), and IL-6 (109.17 ± 4.84 pg/ml vs. 71.73 ± 2.04 pg/ml) significantly increased in the model group, along with their mRNA expression levels in mouse skin tissues (all P < 0.001) ; compared with the model group, the treatment group showed alleviated psoriatic manifestations, and significant reductions in the levels of inflammatory factors TNF-α (low-dose, high-dose, and positive control groups: 420.80 ± 29.30 pg/ml, 322.33 ± 9.40 pg/ml, 322.97 ± 12.16 pg/ml, respectively), IL-1β (98.69 ± 4.49 pg/ml, 89.02 ± 1.56 pg/ml, 88.88 ± 2.08 pg/ml, respectively), and IL-6 (94.07 ± 3.76 pg/ml, 80.54 ± 3.30 pg/ml, 83.21 ± 3.18 pg/ml, respectively), as well as in their mRNA expression levels (all P < 0.001). In in vitro fibroblast experiments, compared with the control group, the model group exhibited a significant elevation in the supernatant levels of IL-1β (126.42 ± 3.56 pg/ml vs. 34.81 ± 0.44 pg/ml), IL-6 (459.44 ± 9.35 pg/ml vs. 115.51 ± 7.26 pg/ml), CXCL1 (2 434.88 ± 127.63 pg/ml vs. 762.85 ± 30.60 pg/ml) and CXCL12 (3 542.14 ± 35.86 pg/ml vs. 2 095.86 ± 45.12 pg/ml), the expression levels of their mRNAs (all P < 0.001), as well as the protein expression levels of SFRP2, Wnt3a, and β-catenin; after intervention with HLJDT-XJDH-containing serum, all the above indices significantly decreased (all P < 0.001). However, when 20% drug-containing serum intervention was administered simultaneously, the expression of inflammatory factors and chemokines in fibroblasts was significantly higher in the SFRP2 overexpression group than in the non-overexpression group (all P < 0.01). When fibroblasts were co-cultured with HaCaT cells, the model group showed significantly increased cell viability but a decreased apoptosis rate of HaCaT cells compared with the control group, while the low- and high-dose intervention groups showed significantly decreased cell viability but increased apoptosis rates of HaCaT cells compared with the model group (all P < 0.05) . Conclusion:HLJDT-XJDH may exert therapeutic effects in psoriasis by downregulating the SFRP2/Wnt/β-catenin signaling pathway, thereby inhibiting fibroblast activation and inflammatory process, which subsequently suppresses the proliferation of keratinocytes and the activation of inflammatory cells.

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.