Objective To rapidly evaluate the efficacy,safety,and cost-effectiveness of venetoclax(Ven)in non-M3 acute myeloid leukemia(AML),and to provide an evidence-based basis for rational clinical treatment.Methods PubMed,Cochrane Library,Embase,CNKI,WanFang Data databases,and relevant health technology assessment(HTA)websites were searched to collect relevant literature and reports on Ven treatment for non-M3 AML,with a search timeframe from the establishment of the database/website to November 1st,2024.Two researchers independently screened literature,extracted data,and assessed quality,and then qualitatively described and analyzed the results.Results A total of 11 pieces of literature were included,including 5 systematic reviews/Meta-analysis,4 pharmacoeconomic studies,and 2 HTA reports.In terms of efficacy,compared with the control group,non-M3 AML patients receiving Ven treatment had a higher clinical remission rate(P<0.05),a longer event-free survival(EFS)(P<0.05)and a similar or longer overall survival(OS)(P<0.05).Regarding safety,compared to Azacitidine(Aza)monotherapy,Ven+Aza resulted in a higher likelihood of febrile neutropenia in non-M3 AML patients(P<0.05).Non-M3 AML patients receiving Ven+low-dose cytarabine(LDAC)had a higher risk of developing thrombocytopenia compared with LDAC monotherapy(P<0.05).However,the early 30-day mortality rate was lower in the Ven+chemotherapy group than that in the chemotherapy alone group(P<0.05),presenting an acceptable security profile overall.In terms of cost-effectiveness,Ven was cost-effective in non-M3 AML patients compared with the control group.Conclusion Ven has manifested remarkable efficacy and acceptable security profile among patients with non-M3 AML,thus proving to be a medium to long-term cost-effective treatment modality.

Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.

Objective To rapidly evaluate the efficacy,safety,and cost-effectiveness of venetoclax(Ven)in non-M3 acute myeloid leukemia(AML),and to provide an evidence-based basis for rational clinical treatment.Methods PubMed,Cochrane Library,Embase,CNKI,WanFang Data databases,and relevant health technology assessment(HTA)websites were searched to collect relevant literature and reports on Ven treatment for non-M3 AML,with a search timeframe from the establishment of the database/website to November 1st,2024.Two researchers independently screened literature,extracted data,and assessed quality,and then qualitatively described and analyzed the results.Results A total of 11 pieces of literature were included,including 5 systematic reviews/Meta-analysis,4 pharmacoeconomic studies,and 2 HTA reports.In terms of efficacy,compared with the control group,non-M3 AML patients receiving Ven treatment had a higher clinical remission rate(P<0.05),a longer event-free survival(EFS)(P<0.05)and a similar or longer overall survival(OS)(P<0.05).Regarding safety,compared to Azacitidine(Aza)monotherapy,Ven+Aza resulted in a higher likelihood of febrile neutropenia in non-M3 AML patients(P<0.05).Non-M3 AML patients receiving Ven+low-dose cytarabine(LDAC)had a higher risk of developing thrombocytopenia compared with LDAC monotherapy(P<0.05).However,the early 30-day mortality rate was lower in the Ven+chemotherapy group than that in the chemotherapy alone group(P<0.05),presenting an acceptable security profile overall.In terms of cost-effectiveness,Ven was cost-effective in non-M3 AML patients compared with the control group.Conclusion Ven has manifested remarkable efficacy and acceptable security profile among patients with non-M3 AML,thus proving to be a medium to long-term cost-effective treatment modality.

Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.

Objective To evaluate the efficacy,safety and cost-effectiveness of tofacitinib in the treatment of ulcerative colitis using a rapid health technology assessment,and to provide an evidence-based basis for rational clinical use and decision-making.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP and relevant HTA websites and databases were electronically searched to collect high-quality clinical evidence and economic evaluation literature of tofacitinib in the treatment of ulcerative colitis from inception to July 31,2024.The results were qualitatively analyzed by two researchers after independently screening the literature,extracting information and evaluating quality.Results A total of 17 studies were included,including 1 HTA report,9 systematic reviews/Meta-analyses,and 8 pharmacoeconomic studies.In terms of efficacy,the clinical response rate,clinical remission rate,mucosal healing rate,endoscopic remission rate and short-term colectomy rate were significantly improved by the treatment of tofacitnib in ulcerative colitis patients(P＜0.05).In terms of safety,tofacitinib was similar to placebo in the incidence of adverse events,serious adverse events,withdrawal from treatment due to adverse events,incidence of serious infections,and overall mortality(P＞0.05),with only a slight increase in the incidence of infections(P＜0.05).In terms of cost-effectiveness,the treatment of moderate-to-severe ulcerative colitis with tofacitinib was cost-effective compared with conventional therapy or other biologics in many countries including China.Conclusion Tofacitinib is effective and safe in the treatment of ulcerative colitis,and is significantly cost-effective for moderate-to-severe ulcerative colitis patients.Since it is still an off-label drug used for treating ulcerative colitis in China,the efficacy,safety and cost-effectiveness of tofacitinib need to be further evaluated based on the real-world clinical research and medical background in China in the future.

Objective To explore the significance of serum β-nerve growth factor(β-NGF)and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)testing in clinical diagnosis and prognosis assessment in patients with pulmonary heart disease(PHD)complicated with pulmonary artery hypertension(PAH).Methods A 1:1 case-control study was conducted in Daxing District People's Hospital of Beijing from January 2019 to June 2022,in which 86 patients with PHD complicated with PAH and 86 patients with isolated PHD were selected as case group and control group.Retrospective analysis was conducted.The case group was divided into mild PAH group(n=39),moderate PAH group(n=25)and severe PAH group(n=22)according to pulmonary artery systolic pressure(PASP).Meanwhile,the case group was divided into good prognosis group(n=75)and poor prognosis group(n=11)based on the outcomes after one year of discharge.Demographic data and laboratory examination indicators of study subjects were collected,and serum β-NGF and TRAIL levels were measured using enzyme-linked immunosorbent assay(ELISA).Pearson product-moment correlation analysis was used to assess the relationship among β-NGF,TRAIL and PASP.Logistic regression analysis was performed to identify factors influencing PAH in patients with PHD.ROC curve was used to evaluate the diagnostic value of β-NGF and TRAIL for PAH.Cox proportional hazards regression analysis was carried out to assess the relationship among β-NGF,TRAIL and poor prognosis in patients with PHD complicated with PAH,and ROC curve was used to evaluate its predictive value for poor prognosis.Result Compared with control group,the duration of PHD in case group was longer(8.63±1.27 years vs 5.49±1.15 years),and serum β-NGF level(26.97±8.25 ng/ml vs 22.14±7.32 ng/ml)and TRAIL level(2.83±0.76 ng/ml vs 1.71±0.68 ng/ml)were increased,with significant differences(t=17.006,4.064,10.183,all P＜0.05).Serum β-NGF and TRAIL had certain diagnostic values for PAH in PHD patients,with AUC of 0.842 and 0.838,respectively.And the combined diagnostic AUC was 0.920,which was higher than that of single indicators(Z=3.416,3.508,all P＜0.05).Serum β-NGF(23.26±5.13 ng/ml,27.83±5.57 ng/ml,32.57±6.02 ng/ml)and TRAIL(2.24±0.65 ng/ml,2.89±0.71 ng/ml,3.81±0.90 ng/ml)levels among patients with mild PAH,moderate PAH,severe PAH were sequentially elevated,and the differences were significant(F=20.624,31.972,all P＜0.05).Serum β-NGF and TRAIL were positively associated with PASP(r=0.673,0.659,P＜0.05).Serum β-NGF(36.34±8.05 ng/ml)and TRAIL(3.49±1.01 ng/ml)levels in poor prognosis group were higher compared to good prognosis group(25.59±7.28 ng/ml,2.73±0.89 ng/ml),and the differences were significant(t=4.516,2.604,all P＜0.05).Logistic regression analysis showed that,the PHD duration[OR(95％CI):1.784(1.135～2.806)],β-NGF[OR(95％CI):1.976(1.108～3.523)]and TRAIL[OR(95％CI):1.866(1.123～3.101)]were independent risk factors for occurrence of PAH in patients with PHD(all P＜0.05).Multivariate COX proportional risk regression results showed that PHD duration[OR(95％CI):1.167(1.082～1.364)],β-NGF[OR(95％CI):1.322(1.134～1.649)],TRA-IL[OR(95％CI):1.259(1.087～1.590)]were independent risk factors for poor prognosis in patients with PHD complicated with PAH(all P＜0.05).Serum β-NGF and TRAIL could predict the poor prognosis in patients with PHD complicated with PAH,with AUC of 0.863 and 0.881,respectively.The combined diagnostic AUC was 0.907,which was higher than that of single indicators(Z=2.905,3.128,all P＜0.05).Conclusion Elevated serum β-NGF and TRAIL were independent risk factors for PAH and were associated with severity of PAH.Early combined detection of β-NGF and TRAIL can improve the diagnostic value for PAH and predict poor prognosis of patients.

Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.

Objective To explore the therapeutic effects of different doses of radioactive iodine-131 on patients with hyperthyroidism.Methods A total of 574 patients with hyperthyroidism treated in the First Affiliated Hospital of Xinxiang Medical University from April 2020 to April 2023 were sampled for this study and were divided evenly into the observation group and the control group by a random number table,with 287 patients in each group.The control group was treated with high-dose radioactive iodine-131(＞10-15 mCi),while the observation group was provided with low-dose radioactive iodine-131(5-10 mCi).The therapeutic effects were estimated six months after treatment.Data of the two groups of patients before treatment and 3 and 6 months after treatment were compared,including the levels of thyroid hormone(FT4),free triiodothyronine(FT3),and thyroid-stimulating hormone(TSH),which were measured through the fluorescence immunochromatography of serum(obtained by centrifugation of 3 mL fasting venous blood),and the tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),interleukin-6(IL-6),and IL-1,which were measured through the enzyme-linked immunosorbent assay of serum.The salivary gland uptake index and salivary gland secretion index of the patients before treatment and 3 and 6 months after treatment were measured through radionuclide imaging.The incidence of adverse reactions during treatment was documen-ted.The incidence of hypothyroidism in both groups was evaluated 6 months after treatment.Results The total effective rate of the observation group and the control group was 83.27％(234/281)and 92.88％(261/281),respectively,and that of the observation group was significantly higher(x2=12.353,P＜0.05).The FT4,FT3,and TSH levels of the two groups before treatment showed no statistical discrepancy(P＞0.05).According to data collected 3 and 6 months after treatment,FT4 and FT3 levels of both groups significantly decreased,while TSH increased(P＜0.05)compared to corresponding pre-treatment levels;FT4 and FT3 levels of both groups observed 6 months after treatment were significantly lower than those observed 3 months before,in contrast to the growing TSH trend(P＜0.05).At 3 and 6 months after treatment,FT4 and FT3 levels of the observation group were significantly lower than those of the control group,while TSH levels were significantly higher(P＜0.05).The salivary gland uptake index and salivary gland secretion index between the two groups before treatment showed no statistical discrepancy(P＞0.05).At 3 and 6 months after treatment,such indexes of both groups obviously decreased(P＜0.05).However,those observed 6 months after treatment were higher than three months before(P＜0.05).At 3 months after treatment,the salivary gland uptake index and salivary gland secretion index of the observation group were notably higher than the control group(P＜0.05);at 6 months after treatment,no statistical discrepancy was observed between the two groups in terms of the two indexes(P＞0.05).Before treatment,there was no statistical difference in TNF-α,TGF-β1,IL-6,and IL-1 levels between the two groups(P＞0.05).At 3 and 6 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of both groups decreased significantly from pre-treatment levels(P＜0.05),and the data observed 6 months after treatment were still lower than those observed 3 months after treatment(P＜0.05).At 3 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of the observation group were significantly lower than those of the control group(P＜0.05);at 6 months after treatment,no statistical difference was observed between the two groups(P＞0.05).The incidence of adverse reactions during treatment in the control group and the observation group was 16.38％(47/287)and 8.01％(23/287),respectively,and that of the observation group was significantly lower than the other group(x2=8.457,P＜0.05).At 6 months after treatment,the incidence of hypothyroidism in the control group and the observation group was 12.46％(35/281)and 3.56％(10/281),respectively,and that of the observation group was significantly lower than that in the control group(x2=15.098,P＜0.05).Conclusion Low doses of radioactive iodine-131 work better in the treatment of hyperthyroidism and can effectively alleviate inflammation and salivary gland dysfunction,with less risk of inducing hypothyroidism and adverse reactions.

Objective To evaluate the efficacy,safety and cost-effectiveness of tofacitinib in the treatment of ulcerative colitis using a rapid health technology assessment,and to provide an evidence-based basis for rational clinical use and decision-making.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP and relevant HTA websites and databases were electronically searched to collect high-quality clinical evidence and economic evaluation literature of tofacitinib in the treatment of ulcerative colitis from inception to July 31,2024.The results were qualitatively analyzed by two researchers after independently screening the literature,extracting information and evaluating quality.Results A total of 17 studies were included,including 1 HTA report,9 systematic reviews/Meta-analyses,and 8 pharmacoeconomic studies.In terms of efficacy,the clinical response rate,clinical remission rate,mucosal healing rate,endoscopic remission rate and short-term colectomy rate were significantly improved by the treatment of tofacitnib in ulcerative colitis patients(P＜0.05).In terms of safety,tofacitinib was similar to placebo in the incidence of adverse events,serious adverse events,withdrawal from treatment due to adverse events,incidence of serious infections,and overall mortality(P＞0.05),with only a slight increase in the incidence of infections(P＜0.05).In terms of cost-effectiveness,the treatment of moderate-to-severe ulcerative colitis with tofacitinib was cost-effective compared with conventional therapy or other biologics in many countries including China.Conclusion Tofacitinib is effective and safe in the treatment of ulcerative colitis,and is significantly cost-effective for moderate-to-severe ulcerative colitis patients.Since it is still an off-label drug used for treating ulcerative colitis in China,the efficacy,safety and cost-effectiveness of tofacitinib need to be further evaluated based on the real-world clinical research and medical background in China in the future.

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
Mice ; Animals ; Hyperalgesia/metabolism* ; Microglia/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Ganglia, Spinal/metabolism*