Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To investigate the clinical features of hypopituitarism with nonalcoholic fatty liver disease (NAFLD) in children after sellar tumor surgery and the association between hypopitarism and NAFLD in children. Methods A retrospective analysis was performed for the clinical data of children with hypopituitarism and NAFLD after sellar tumor surgery who were followed up regularly in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2017 to December 2021, and their clinical features were analyzed. Results There were 32 children with regular follow-up and complete clinical data after sellar tumor surgery, and 10 children (31.25%) developed NAFLD, among whom there were 5 boys and 5 girls. Among these 10 children, 9 had craniopharyngioma and underwent surgical treatment, and 1 had germinoma and underwent local radiotherapy. The 10 children had a median age of 8.4(6.29.8) years at the diagnosis of hypopituitarism and a median age of 11.9(8.7-12.6) years at the diagnosis of NAFLD. The median number of years from the diagnosis of hypopituitarism to the diagnosis of NAFLD was 2.0(1.4-4.0) years. At the diagnosis of NAFLD, all 10 children had obesity, and body mass index (BMI) was increased by 7.26±4.25 kg/m 2 on average since the diagnosis of hypopituitarism; the 10 children had a mean fasting blood glucose level of 4.67±0.55 mmol/L, a mean fasting insulin level of 25.40±5.93 μIU/ml, and a mean HOMA-IR index of 5.26±1.29. Among these 10 children, 9 had hypertriglyceridemia, and 1 had elevated triglyceride, with a mean level of 3.08±1.09 mmol/L; 6 children had hypercholesterolemia, with a mean level of 5.67±1.25 mmol/L; 8 children had high-density lipoprotein cholesterolemia, with a mean level of 3.97±1.27 mmol/L. After the diagnosis of NAFLD, 2 children were treated with recombinant human growth hormone and metformin and achieved reductions in BMI, HOMA-IR, and triglyceride after treatment, and total cholesterol and low-density lipoprotein cholesterol were reduced to the normal range. Conclusion Children may experience weight gain, hypopituitarism, insulin resistance, and dyslipidemia after sellar tumor surgery, which may lead to the onset of NAFLD. Weight management and active pituitary hormone replacement therapy are recommended for such children, as well as routine screening and management of fatty liver disease.

Objective:To examine the effects of heart rate control during hospitalization on short-term prognosis of heart failure in elderly patients.Methods:As a prospective study, 150 elderly patients with heart failure were selected from the Department of Geriatrics, Qilu Hospital of Shandong University.The subjects were divided into an experimental group and a control group by digitally generated random numbers, with 75 individuals in each group.Both groups received conventional anti-heart failure therapy during hospitalization, but patients from the control group had doses of heart rate control drugs adjusted every 2-4 weeks, with no special requirement for the heart rate before hospital discharge.In contrast, patients from the experimental group were given heart rate control drugs with timely dose adjustment to achieve more proactive heart rate control, aiming for a rate <70 beat/min, as long as heart failure symptom improvement and good volume management could be maintained.Values of cardiac function indexes were compared between the two groups at discharge and 6 months after discharge.Heart failure readmission rates within 6 months, cardiovascular disease mortality rates and the incidences of composite endpoint events after readmission due to heart failure aggravation were compared between the two groups.Treatment safety was also evaluated.Results:There was no statistical difference in blood pressure, heart rate, N-terminal pro-B-type natriuretic peptide(NT-pro-BNP), left ventricular ejection fraction(LVEF), left ventricular end systolic diameter(LVESD), or left ventricular end diastolic diameter(LVEDD)between the two groups at admission( P>0.05), and there was no statistical difference in the average length of hospitalization between the two groups( P>0.05). The experimental group had a lower average heart rate and diastolic pressure than the control group at discharge and 6 months latter[at discharge: (61.6±4.2)beat/min(1 mmHg=0.133 kPa) vs.(78.0±7.1)beat/min, (62.1±10.4)mmHg vs.(66.1±10.2)mmHg; at 6 months: (64.7±12.1)beat/min vs.(71.8±11.2)beat/min, (62.8±11.2)mmHg vs.(68.6±10.2)mmHg; P<0.05 or P<0.01]. NT-pro-BNP in the experimental group was significantly lower than that in the control group at discharge[(1 706±1 408)ng/L vs.(2 806±3 812)ng/L, P<0.05]. The absolute values of changes in LVEF(ΔLVEF), LVESD(ΔLVESD)and LVEDD(ΔLVEDD)after 6 months in the experimental group were significantly higher than those in the control group[ΔLVEF: (0.08±0.09) vs.(0.02±0.09), P<0.05; ΔLVESD: (-5.82±7.44)mm vs.(-1.63±6.07)mm, P<0.01; ΔLVEDD: (-2.76±5.52)mm vs.(-0.86±4.44)mm, P<0.05]. The rate of readmission and the incidence of composite endpoint events within 6 months in the experimental group were significantly lower than those in the control group[21.3%(16 cases) vs.36.0%(27 cases), P<0.05]; 25.3%(19 cases) vs.44.0%(33 cases), P<0.05.There was no significant difference in all-cause mortality between the two groups( P>0.05). Conclusions:For elderly patients with heart failure, proactive active heart rate control during hospitalization and a rate <70 beat/min before discharge will improve cardiac function indexes and lower the rate of readmission with exacerbation of heart failure, cardiovascular disease mortality and the incidence of composite end-point events after readmission.This strategy has good safety and is beneficial for short-term prognosis.

Objective:To explore the feasibility of applying plasma with same blood group as kidney donor to ABO incompatible kidney transplantation(ABOi-KT)preconditioning of blood group O recipients with high-titer anti-A/B preformed antibody(IgM/IgG titer ≥1∶256).Methods:A total of 15 cases of blood group O ABOi-KT recipients with high-titer anti-A/B were recruited and divided into two groups of AB( n=8)and kidney donor's blood(KD, n=7)according to plasma type for plasma exchange during preconditioning phase. Clinical data of preconditioning and post-KT were recorded. Results:They received plasmapheresis(PP)(8.1±2.5)sessions in preconditioning phase, including double plasma filtration(DFPP)(4.0±1.4)sessions and plasma exchange(PE)(4.1±2.0)sessions, PP frequency was(0.8±0.1)sessions per day. No hemolysis reaction occurred during preconditioning phase. Anti-A/B titers declined as expected and fulfilled the ABOi-KT criteria(IgM/IgG titers ≤1∶8). KT was performed successfully without antibody-mediated rejection. All of them survived with normal renal function within 90 days post-KT. Levels of serum creatinine at Day 7/30/90 post-KT were(92.9±30.4), (96.2±25.9)and(103.1±28.4)μmol/L; anti-A/B IgM titers at Day 7/30/90 post-KT 1∶1-1∶32, 1∶1-1∶64 and 1∶1-1∶32; anti-A/B IgG titers at Day 7/30/90 post-KT 1∶1-1∶64, 1∶1-1∶64 and 1∶1-1∶32 respectively. No significant differences existed in count/frequency of PP sessions, levels of serum creatinine or anti-A/B titers at each observation point between AB and KD groups( P>0.05). Conclusions:Plasma with the same blood group as kidney donor is feasible for maximizing the intensity of ABOi-KT preconditioning. Favorable outcomes may be achieved through an intensified desensitization strategy on blood group O recipients with high-titer anti-A/B preformed antibody. The potential risks and long-term outcomes should be further explored.

BACKGROUND: Since the diagnostic value of aldosterone to renin ratio (ARR) calculated by plasma renin concentration (PRC) or plasma renin activity (PRA) is still inconclusive, we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA, so as to provide guidance for clinical diagnosis. METHODS: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to March 2021. We included studies that report the true positive, false positive, true negative, and false negative values for the diagnosis of primary aldosteronism, and we excluded duplicate publications, research without full text, incomplete information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. RESULTS: The pooled results showed that ARR (plasma aldosterone concentration [PAC]/PRC) had a sensitivity of 0.82 (95% confidence interval [CI]: 0.78-0.86), a specificity of 0.94 (95% CI: 0.92-0.95), a positive-likelihood ratio (LR) of 12.77 (95% CI: 7.04-23.73), a negative LR of 0.11 (95% CI: 0.07-0.17), and symmetric area under the curve (SAUC) of 0.982, respectively. Furthermore, the diagnostic odds ratio (DOR) of ARR (PAC/PRC) was 180.21. Additionally, the pooled results showed that ARR (PAC/PRA) had a sensitivity of 0.91 (95% CI: 0.86-0.95), a specificity of 0.91 (95% CI: 0.90-0.93), a positive LR of 7.30 (95% CI: 2.99-17.99), a negative LR of 0.10 (95% CI: 0.04-0.26), and SAUC of 0.976, respectively. The DOR of ARR (PAC/PRA) was 155.52. Additionally, we conducted a subgroup analysis for the different thresholds (<35 or ≥35) of PAC/PRC. The results showed that the DOR of the cut-off ≥35 groups was higher than the cut-off <35 groups (DOR = 340.15, 95% CI: 38.32-3019.66; DOR = 116.40, 95% CI = 23.28-581.92). CONCLUSIONS The research results suggest that the determination of ARR (PAC/PRC) and ARR (PAC/PRA) was all effective screening tools for PA. The diagnostic accuracy and diagnostic value of ARR (PAC/PRC) are higher than ARR (PAC/PRA). In addition, within a certain range, the higher the threshold, the better the diagnostic value.
Aldosterone ; Area Under Curve ; Humans ; Hyperaldosteronism/diagnosis* ; Hypertension ; Renin

Obstructive sleep apnea (OSA)is a high incidence of potentially dangerous disease,characterized by intermittent hypoxia or hypercapnia.It is an independent risk factor for ischemic stroke.Currently a number of studies have confirmed OSA closely associated with oxidative stress.In this paper,the complex mechanisms of oxidative stress in the OSA and the occurrence of stroke will be reviewed,such as promoting atherosclerosis,damaging the mitochondria,ischemia -reperfusion injury,ischemic preconditioning.To investigate the relationship between OSA,oxidative stress and stroke from molecular mechanisms.

ABSTRACT:Objective To study the efficacy and safety of oxcarbazepine (OXC)oral suspension on children with different kinds of epilepsy.Methods A total of 83 children with epilepsy were selected from the Pediatric Department of the First Affiliated Hospital of Xi’an Jiaotong University and Xi’an Children’Hospital from June 201 1 to June 2014.They were treated with OXC monotherapy or adjunctive therapy.Use open-label and self-contrast method.The initial dose of OXC was 8 -10 mg/(kg·d),and then was added 10 mg/(kg·d)per 7 days until it reached the minimum effective dose.Generally,the maintenance dose was about 20-40 mg/(kg·d).The follow-up duration was 6 - 12 months.Results 83 cases were eventually included and 5 cases withdrew.We elvaluated the efficacy every 3 months.The results were as follows:the first stage (1,2,3 months)resulted in a 41.0% of full control rate and a 71.8% of total effective rate;the second stage (4,5,6 months)resulted in a 46.2% of full control rate and a 76.9% of total effective rate;the third stage (7,8,9 months)resulted in a 59.0%of full control rate and a 79.5% of total effective rate.There were no significant differences in the efficacy of the three stages.54 cases with partial seizures resulted in a 59.3% of full control rate and a 79.6% of total effective
rate;24 cases with generalized seizure resulted in a 45.8% of full control rate and a 62.5% of total effective rate. There was no statistical significant difference in the efficacy of the two seizure types.43 cases with monotherapy resulted in a 58% of full control rate and a 79% of total effective rate,35 cases with add-on therapy resulted in a 40.0% of full control rate and a 57.1% of total effective rate.24 cases with < 2 resulted in a 41.7% of full control rate and a 62.5% of total effective rate,54 cases with 2-6 resulted in a 59.3% of full control rate and a 83.3% of total effective rate.14 cases of children were reported to have at least one adverse drug reactions,the specific symptoms included emotional instability unstable, hypohidrosis, somnolence, dizzness, headache, vomiting, urorrhea,lack of appetite,aggressive behavior and hypomnesia.Adverse reactions were mild and most of them could subside over time.Conclusion OXC oral suspension has a good efficacy and safety when treating children with partial seizures or generalized tonic-clonic seizures of epilepsy.

Objective To investigate the roles of phosphatidylinositol 3 kinase (PI3K) and phosphorylated Akt (P-Akt) in the pathogenesis of cervical squamous cell carcinoma and condyloma acuminatum.Methods Immunohistochemistry and Western blot were used to detect the expressions of PI3K and P-Akt in tissue specimens from the lesions of 30 cases of cervical squamous cell carcinoma,30 cases of condyloma acuminatum and the prepuce of 15 normal human controls.The average optical density and gray scale values were calculated and analyzed by t test and F test respectively.Results The expressions of PI3K and P-Akt were observed in only the basal layer of the epidermis of control specimens,but in the whole epidermis of condyloma acuminatum tissue specimens.Cervical squamous cell carcinoma tissue specimens displayed a stronger expression of PI3K and P-Akt compared with the control and condyloma acuminatum tissue specimens.As immunohistochemistry revealed,the average absorbance value for PI3K and P-Akt was 0.28 ±0.05 and 0.20 ± 0.07 respectively in cervical squamous cell carcinoma tissue specimens,0.22 ± 0.04 and 0.17 ± 0.03 respectively in condyloma acuminatum tissue specimens,and 0.16 ± 0.04 and 0.10 ± 0.02 respectively in the control tissue specimens; significant differences were observed in the expressions of PI3K and P-Akt among the three groups of tissue specimens (F =44.87,20.64,respectively,both P ＜ 0.01 ).The results of Western blot were consistent with those of immunohistochemistry,and there was a significant difference in the gray scale value for PI3K and P-Akt between cervical squamous cell carcinoma,condyloma acuminatum and control tissue specimens (3.48 ± 0.48 vs.1.99 ± 0.11 vs.1.00 ± 0.03,F=354.83,P＜ 0.01; 3.33 ± 0.26 vs.1.96 ± 0.11 vs.1.00 ± 0.03,F=302.33,P＜ 0.01 ).Conclusions The PI3K/Akt signaling pathway is abnormally activated in condyloma acuminatum and cervical squamous cell carcinoma,and human papilloma virus may cause the abnormal proliferation of infected epithelium likely by affecting the upregnlated expression of PI3K/P-Akt.

Objective To observe the curative effect, safety and patient's satisfaction degree of combining compound betamethasone with anisodamine injection in the blocking treatment of eyebrow alopecia areata.Methods A total of 66 cases were randomly divined into two groups: patients were treated by compound betamethasone ( group A) and combining compound betamethasone with anisodamine ( group B). The drugs were injected from the middle of eyebrow alopecia areata to two sides by the standard of 0. 2 ml/cm2 in both groups one time a month. The curative effect of the all cases were observed at 1, 2 and 3 months after treatment. The safety of them were evaluated based on incidence rate of the side effect and their satisfactory degree were evaluated based on subjective reception 3 months after treatment. Results The effective rates in the group B were 58.82 %, 73.53 % and 88.23 % by turns at 1,2 and 3 months after treatment, and those in the group A were 31.25 %, 53.13 % and 71.88 %, respectively. The curative effect in the group B was better than that in the group A (P ＜ 0. 05), and the incidence rate of side effect in the group B was similar to that in the group A (P＞0.05) and the patient's satisfaction degree in group B was better than that in group A (P ＜0. 05) 3months after treatment. Conclusion The compound betamethasone combined with anisodamine injection in the treatment of eyebrow alopecia areata has superior curative efficacy, more safety and higher satisfactory degree in the patients.

Objective To investigate the role of phosphorylated extracellular signal-regulated kinase (p-ERK), mitogen-activated protein kinase (MAPK)/ERK kinase (MEK), and nuclear factor-κB (NF-κB) in the pathogenesis of psoriasis vulgaris. Methods Immunohistochemistry and Western blot were used to detect the expression of p-MEK, p-ERK and p-NF-KB in tissue samples from 30 patients with psoriasis vulgaris and 15 normal human controls. The average optical density of immunostaining and relative grey scale of immuno-bloting were calculated. Results The average optical density of immunostaining for p-MEK, p-ERK and p-NF-KB was 0.36 ± 0.03, 0.36 ± 0.04 and 0.26 ± 0.04, respectively in lesion samples of psoriasis, significantly higher than that in normal control tissue (0.22 ± 0.02, 0.18 ± 0.03 and 0.16 ± 0.03, all P < 0.01). A significant increase was also observed in the relative grey scale of p-MEK, p-ERK and p-NF-κB in psoriatic lesions compared with the normal controls (1.41 ± 0.14 vs 0.54 ± 0.10, 2.35 ± 0.34 vs 1.86 ± 0.12, 1.07 ± 0.15 vs 0.87 ± 0.08, all P < 0.01). Conclusions The expressions of p-MEK, p-ERK and p-NF-κB are enhanced in lesions of psoriasis vulgaris, and the abnormal activation of upstream and downstream molecules in the MAPK signaling pathways might be involved in the pathogenesis of psoriasis.