OBJECTIVE To provide reference for optimizing or formulating unified evaluation methods for evidence and recommendation in expert consensus on off-label use of drugs. METHODS Retrieved from CNKI， Wanfang data， VIP， CBM， PubMed and Web of Science， Chinese expert consensuses on off-label use of drugs involving evaluation methods for evidence and recommendations were collected from the inception to August 1， 2024. After screening the literature and extracting relevant data， descriptive statistical analysis was conducted. RESULTS & CONCLUSIONS Among the 32 articles included， 14 articles （43.8%） used Micromedex’s Thomson grading system， only 7 articles （21.9%） considered economic factors when forming recommendations， 10 articles （31.3%） reported the conflicts of interest； only 2 articles （6.3%） involved experts in the field of evidence-based medicine methodology. There were differences in the sources of evidence， factors considered in forming recommendations， and the grading standards for evidence and recommendations among different expert consensus evidence evaluation methods. There were also differences in evidence levels and recommendation strength of the same drug off-label use in different expert consensus. It is recommended that in future consensus-building processes， greater attention should be paid to potential conflicts of interest among participants， collaboration with methodological experts should be enhanced， and efforts should be expedited to establish unified standards for evaluating evidence and recommendation methodologies.

ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction （SWD） at different doses on atherosclerosis （AS） in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE^-/- mice were randomly divided into six groups： blank control group， model group， low-dose， medium-dose， and high-dose SWD groups， and positive control group. Firstly， the AS mouse model was created by feeding mice a high-fat diet. After successful modeling， the low-， medium-， and high-dose SWD groups were intragastrically administered with SWD at 0.65， 1.3， 2.6 g·kg^-1， respectively. The positive control group was intragastrically administered with 30 mg·kg^-1 of atorvastatin calcium aqueous solution， while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage， all administered for 12 weeks. During the administration period， the general condition of the mice was observed and recorded daily. Before sampling， color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in aortic tissue in mice， and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum lipid indices and the levels of interleukins （IL-1β， IL-4， IL-6， and IL-10） and tumor necrosis factor-α （TNF-α） in mice. Protein expression levels of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group， the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo， suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation， fibrous connective tissue proliferation， and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue （P<0.01）. ELISA results indicated significantly elevated levels of IL-1β， IL-6， TNF-α， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） in mouse serum （P<0.01）， as well as significantly decreased levels of IL-4， IL-10， and high-density lipoprotein （HDL） （P<0.01）. Western blot results showed that the expression of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue increased significantly （P<0.01）. Compared with those in the model group， mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group， the aortic vascular wall echoes were weakened， and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD （P<0.05）. In the medium-dose SWD group， serum levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）， while those of IL-4 and IL-10 were significantly increased （P<0.01）. In the high-dose SWD group， levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.01）， while IL-4， IL-10， and HDL were significantly increased （P<0.01）. The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group （P<0.05）， and IKKα， IKKβ， and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups （P<0.05， P<0.01）. ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway， thereby reducing inflammation， plaque area， and lipid content in the body.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Objective:To compare the efficacy, dosage, and safety of dupilumab combined with minocycline or with minocycline and systemic glucocorticoids (sGC) versus minocycline alone or in combination with sGC in patients with bullous pemphigoid (BP) .Methods:A retrospective cohort study was conducted on BP patients who visited the Department of Dermatology, Peking University First Hospital from March 2021 to June 2022 and were treated with one of the following two therapeutic regimens: minocycline alone or in combination with sGC (M-MG group), and dupilumab combined with minocycline or with minocycline and sGC (MD-MGD group). Disease control rates, time to disease control, complete remission rates, time to complete remission, BP disease area index (BPDAI) scores, drug usage, time to pruritus relief, relapse rates, and occurrence rates of adverse reactions were compared between the two groups. Survival analysis was performed using Kaplan-Meier (KM) curves and Log-rank test. Confounders were controlled by 1∶1 matching on the propensity score in the two groups.Results:A total of 164 patients were collected, including 110 in the M-MG group (62 males and 48 females, aged 74.6 ± 12.8 years) and 54 in the MD-MGD group (33 males and 21 females, aged 74.6 ± 13.3 years). After two-week follow-up, there was no significant difference in the disease control rate between the two groups ( P = 0.341); however, the minocycline dose, proportion of patients using sGC, sGC dose, and cumulative sGC dose were all significantly higher in the M-MG group than in the MD-MGD group (all P < 0.05). A total of 152 patients (92.7%) achieved disease control in the two groups during the follow-up, while the disease control rate and time to disease control did not differ between the two groups (both P > 0.05); 52 patients (31.7%) achieved complete remission, there was no significant difference in the complete remission rate between the MD-MGD group (16/54, 29.6%) and M-MG group (36/110, 32.7%; χ2 = 0.16, P = 0.689), but the time to complete remission ( M[ Q1, Q3]) was significantly shorter in the MD-MGD group (98.5[78.0, 185.2] days) than in the M-MG group (223.5 [175.2, 277.0] days, P = 0.001). KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.024). A total of 73 patients (44.5%) recorded the time to pruritus relief during the follow-up, and the MD-MGD group showed significantly shorter time to pruritus relief (54 patients, 14.0 [3.0, 14.0] days) compared with the M-MG group (19 patients, 14.0 [7.0, 19.0] days; P = 0.015). After propensity score matching, each group included 42 patients; during the follow-up, there was no significant difference in the complete remission rate between the M-MG group and MD-MGD group ( P > 0.05), but the time to complete remission was significantly longer in the M-MG group than in the MD-MGD group ( P = 0.019); KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.041). Among the 164 patients, adverse reactions occurred in 58 (35.4%), grade 3 or more severe adverse reactions occurred in 11 (6.70%), but no dupilumab-related adverse reactions were reported. Conclusions:Compared with minocycline alone or in combination with sGC in the treatment of BP, the dupilumab combination therapy could relieve pruritus and result in complete remission in a shorter time. Additionally, dupilumab could help to accelerate the reduction in dosages of sGC and minocycline, with few adverse reactions and favorable safety.

Objective:To analyze the short- and medium-term efficacy, factors influencing the efficacy, and safety of dupilumab alone or in combination for the treatment of bullous pemphigoid (BP) .Methods:A single-center retrospective cohort study was conducted. Clinical data were collected from adult BP patients, who were regularly followed up and treated with dupilumab at the Department of Dermatology, Peking University First Hospital between March 2021 and June 2022. Dupilumab was administered subcutaneously every 2 weeks at a dose of 300 mg (except for the initial dose being 600 mg). Previous medications included glucocorticoids, minocycline, immunosuppressants, etc., and their dose remained unchanged or decreased according to patient condition. The short- and medium-term response rates were evaluated at weeks 2 and 16 after the first injection of dupilumab, respectively. Multivariate logistic regression analysis was conducted to identify factors influencing the disease control rate at week 2, and odds ratios ( ORs) were calculated; a multivariate Cox regression model was employed to analyze factors influencing the disease control rate within 16 weeks of follow-up, and hazard ratios ( HRs) were calculated; multiple linear regression analysis was performed to determine factors associated with the time to pruritus relief. Results:A total of 104 BP patients were eligible, including 60 males and 44 females; they were aged 75.6 ± 12.8 years, and the disease duration ( M [ Q1, Q3]) was 4.0 (2.0, 17.0) months. According to the percentage of the lesion area to the total body surface area, the disease severity was graded, and there were 17 mild cases, 30 moderate cases, 31 severe cases, and 26 extremely severe cases; 56 patients (53.9%) were treated with dupilumab combined with oral glucocorticoids at doses of 20.0 (15.0, 30.0) mg/d. At week 2 after the start of treatment, 63 patients (60.6%) achieved disease control, and 37 (35.6%) achieved marked disease control, resulting in a short-term response rate of 96.2%. Fifty-five patients were followed up for 16 weeks, 54 (98.2%) achieved improvement, and the systemic glucocorticoid dose was reduced to 10.0 (10.0, 17.5) mg/d. Disease control was achieved in 92 of 104 patients (88.5%) within 16 weeks, with the time to disease control being 14.0 (13.0, 26.0) days and the time to pruritus relief being 12.0 (3.0, 14.0) days. Multivariate logistic regression analysis showed that the higher the baseline disease severity, the lower the disease control rate at week 2 (compared with extremely severe cases, mild cases: OR = 37.655, 95% CI: 3.664, 386.981; moderate cases: OR = 12.143, 95% CI: 2.609, 56.528; severe cases: OR = 4.014, 95% CI: 1.121, 14.369, all P < 0.05). Multivariate Cox regression analysis showed that compared with severe BP patients, mild ( HR = 2.478, 95% CI: 1.200, 5.114, P = 0.014) and moderate BP patients ( HR = 2.076, 95% CI: 1.067, 4.038, P = 0.031) were more likely to achieve disease control during the 16-week treatment and follow-up. Multiple linear regression analysis revealed that the disease duration significantly influenced the time to pruritus relief ( P = 0.006), and the longer the disease duration, the longer the time to pruritus relief. During the follow-up, 13 adverse events occurred in 11 patients (10.6%), including 6 with pulmonary infections, 2 with heart failures, 1 with scabies, 1 with viral conjunctivitis, 1 with pericardial effusion (with a high likelihood of idiopathic pericarditis), 1 with organ failure, and 1 with intracerebral hemorrhage, but none of them were clearly related to dupilumab and most of them did not affect the treatment continuation; 3 deaths were reported, including 2 due to organ failures and 1 due to lung infection, which were all unrelated to dupilumab as determined by specialists. Conclusion:Dupilumab combination therapy for BP could result in rapid disease control, relieve pruritus, and reduce systemic glucocorticoid dosage, with a good safety profile.

Objective To investigate the food allergy situation of children in Changping District of Beijing,and to explore the influence of allergic family history,gender and mode of delivery on food allergy in children,the distribution of food allergy in different age groups,the types of food allergy that are easy to cause in this area,and the comorbidities of food allergy.Methods A total of 515 children aged 0 to 14 years who were admitted to the general pediatric outpatient and emergency department and inpatient of Beijing Changping Hospital from April to November 2023.Using immunoblotting to detect specific immunoglobulin E in the serum of pediatric patients,and using SPSS 26.0 statistical software to perform binomial tests on gender and delivery mode non parameters;Using custom Excel functions to statistically analyze the family history of allergies,the number of people in different age groups,and the frequency of allergic foods in each group;Use a self-made mini program to statistically analyze the combination of comorbid allergic diseases.Results ① The number of male children with food allergies(306 cases)was higher than that of female children(209 cases),and the difference was statistically significant(P＜0.05).(2)There were 109 cases of pediatric patients with parents who had no history of allergic diseases,accounting for 21.17％of the total cases;There were a total of 406 cases where at least one parent had a family history of allergies,accounting for 78.83％of the total cases.Among them,228 cases(44.27％)had one parent with a history of allergies,and 178 cases(34.56％)had both parents with a history of allergies.③ Among 515 children with positive food allergens,there were 10 cases(1.94％)in infancy,37 cases(7.19％)in early childhood,235 cases(45.63％)in preschool,192 cases(37.28％)in school age,and 41 cases(7.96％)in adolescence.The highest positivity rate for food allergens is in milk(444 times),followed by egg white(70 times),cashew nuts(57 times),crab(37 times),beef(26 times),mango(24 times),shrimp(21 times),pineapple(6 times),and shellfish(1 time).Milk protein is the most common allergen in all age groups.(4)Among 515 children with food allergies,399 cases were single food allergies,accounting for 77.47％;116 cases of multiple food allergies(2 or more types of food allergies),accounting for 22.53％.⑤ The most common comorbidity of food allergies is food allergy related gastrointestinal diseases combined with allergic rhinitis,with a total of 267 cases;Secondly,there were 192 cases of allergic rhinitis combined with chronic cough,and 124 cases of food allergy related gastrointestinal diseases combined with chronic cough.Conclusion Milk is the main allergen of food allergy in people of age 14 and under,and gastrointestinal symptoms are the most common in children with food allergy.

Objective To investigate the effect of intrarectal local anesthesia (IRLA) with heated oxybuprocaine gel on pain during transrectal ultrasound guided prostate biopsy (TRUSPB).Methods A total of 150 cases patients who underwent TRUSPB in Huzhou Central Hospital from January to June 2023 were prospectively taken into.The patients were randomly divided into group A (routine group),group B (oxybuprocaine gel for IRLA at room temperature) and group C (oxybuprocaine gel for IRLA at 40℃),with 50 cases in each group.Nurses who were unaware of the anesthesia type used visual analog scale (VAS) to score the pain level of patients at each stage (VAS Ⅰ:when the ultrasound probe was inserted into the rectum;VAS Ⅱ:during the biopsy;VAS Ⅲ:30 minutes after biopsy),and the incidence of complications after biopsy were compared.Results The VAS Ⅱ score of group C was lower than that of group A and group B,and the difference was statistically significant (P<0.05).There was no statistically significant difference (P>0.05) in the VAS Ⅰ,VAS Ⅲ scores,and incidence of complications after biopsy among the three groups.There was no allergic reaction to oxybuprocaine gel.Conclusion In TRUSPB,IRLA with heated oxybuprocaine gel can effectively control pain without increasing incidence of complications.

Objective To establish a new program of blood cell processing apparatus(NGL-BBS)for the preparation of washed mixed plateletsand to study the effect on biological activity of platelets compared with tradi-tional manual method.Methods Mixed concentrated platelets were separated and prepared from whole blood by white membrane method.Blood cell processing apparatus with new program set(experimental group)and manual method(control group)was used for thepreparation of washed mixed platelets.The expression rate of CD62P and CD63 in the two groups of washed mixed platelets was compared by flow-cytometry.Thrombus elastography(TEG)was used to measure and compare the MA value between the two groups.Results The expression rate of CD62P and CD63 in the experimental group was lower than that in the control group(t = 4.11,P<0.01;t = 10.78,P<0.01).TheTEG MA valueof the experimental group was higher than that of the control group(t = 6.67,P<0.01).Conclusion The present study demonstrates that the use of NGL-BBS for the preparation of washed mixed plate-lets has a lesser impact on biological activity compared to manual preparation methods.

Objective To explore the role and molecular mechanism of Lnc-BM in the occurrence and development of gastric cancer (GC). Methods GC tissues and paired adjacent normal tissues of 36 GC patients were collected, and the expression of Lnc-BM was detected by RT-qPCR. Colony formation and CCK-8 assays were used to investigate the proliferation of GC cells. The migration and invasion properties of GC cells were investigated via Transwell assay. RNA pull-down assay was applied to confirm the interaction between FASTK and Lnc-BM. Western blot assay was used to detect FASTK protein level in Lnc-BM overexpressing or knockdown cells. Mitochondrial respiratory capacity and the related proteins expression levels were detected by Seahorse and Western blot assays, respectively. Lnc-BM stably overexpressing GC cells were constructed and then injected subcutaneously into nude mice. The tumor growth was observed. Results Lnc-BM was highly expressed in GC tissues compared with their paired adjacent normal tissues. Lnc-BM overexpression significantly promoted GC cells proliferation migration and invasion, while Lnc-BM knockdown inhibited GC cells proliferation, migration and invasion (P < 0.05). RNA pull-down experiment demonstrated that Lnc-BM can directly bind to FASTK. Western blot results indicated that overexpression of Lnc-BM increased the protein levels of FASTK, while knockdown of Lnc-BM inhibited the expression of FASTK (P < 0.05). Compared to the control group, overexpression of Lnc-BM increased the levels of mitochondria associated proteins, such as MT-ND6 and TOM20 (P < 0.05). Seahorse results indicated that overexpression of Lnc-BM enhanced mitochondrial respiratory capacity (P < 0.05). Knocking down FASTK in Lnc-BM stably overexpressing cells can reverse the increase in mitochondrial respiratory capacity caused by Lnc-BM overexpression (P < 0.05). In vivo, the results of subcutaneously implanted tumor model in nude mouse showed that Lnc-BM overexpression promoted the tumor growth (P < 0.05). Conclusion Lnc-BM promotes GC progression by regulating mitochondrial respiratory function through the FASTK/MT-ND6 axis.

Abstract: Upon monitoring cytoplasmic aberrant double-stranded DNA, cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines, which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection. However, sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases, aging-associated inflammation, and neurodegenerative pathologies. Herein, we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases, with a particular review of the research and development progress of STING agonists, cGAS inhibitors, and STING inhibitors, aiming to provide some theoretical reference for the future development of cGAS-STING modulators.