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.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

At present, the incidence and mortality of tumors are increasing, and the treatment of tumors has attracted much attention. Radiotherapy is a key method for tumor treatment; however, its effectiveness is often constrained by radioresistance. During tumor radiotherapy, DNA damage response (DDR) is a key factor in the radioresistance of tumor cells. Research has shown that the radiosensitivity of tumor cells can be effectively improved by regulating the expression of key proteins in the DDR pathway. Targeting the DDR signaling pathway has become an effective strategy to reduce tumor radioresistance. This article focuses on the mechanisms, clinical research status, limitations, and current challenges associated with the key DDR proteins DNA-PKcs, ATM, ATR, and PARP as therapeutic targets for tumor radiotherapy sensitization, in order to provide a reference for the development of radiotherapy sensitization agents.

Objective:To study the clinical and genetic characteristics of familial paroxysmal exercise-induced dyskinesia with Parkinson-like manifestations in the elderly.Methods:Clinical data of 9 family members were analyzed, including 2 patients(both received treatment)consenting to appropriate therapy and prediction protocols.DNA was extracted from peripheral blood samples, and then second-generation sequencing mutation screening.Results:The tremor of two probands in the family was completely brought under control by oxcarbazepine treatment.In 5 family members, a heterozygous mutation of base G>C in exon 2 c. G366C: P.QCon122H at position 29824741 of the PRRT2 gene was found, resulting in the mutation of the amino acid at 122 from glutamine to histidine, which was predicted by SIFT and M-CAP to be harmful.Sanger sequencing of pedigree samples showed that the sisters, brothers and nephews of the proband were heterozygous and their nieces were of the wild type.Conclusions:Q122 of PRRT2 protein can cause the Parkinson-like limb tremor phenotype, and antiepileptic drugs are also effective for paroxysmal exercise-induced dyskinesia in the elderly.

Objective:To study the effect of psoralen on the proliferation, invasion and migration of HTB-47 and CRL-1932 renal cancer cells cultured in vitro, and to further explore the internal mechanism of psoralen inhibiting renal cancer.Methods:The experimental group was HTB-47 and CRL-1932 renal cancer cells treated with dimethyl sulfoxide solution containing 30 μg/ml psoralen, and the control group was renal cancer cells treated with dimethyl sulfoxide. Scratch test, CCK8, Transwell, and Western blot were used to detect the effect of psoralen on renal cancer cells.Results:Compared with the control group, the proliferation, invasion and migration of renal cancer cells treated with psoralen in the experimental group were significantly inhibited. In the renal cancer cells treated with psoralen, the protein expression levels of MKI67, PCNA, MMP2 and MMP9 were significantly decreased (all P<0.05). Conclusions:Psoralen can significantly inhibit the proliferation, invasion and migration of HTB-47 and CRL-1932 renal cancer cells in vitro. The mechanism may be to inhibit the progression of renal cancer by regulating MKI67, PCNA, MMP2 and MMP9.

Objective:To explore the application value of artificial intelligence (AI) in image post-processing of reconstructed CTA based on CT cerebral perfusion (CTP).Methods:Clinical and radiological data of 100 patients suspected of cerebrovascular diseases in Hebei General Hospital from January to July 2020 were retrospectively selected. All patients were divided into A and B group on average according to the different examination schemes. Cerebral CTP examination was performed in group A (the temporal maximum intensity projective data set generated by the first 5 time phases in the maximum period of the difference between arteriovenous CT values selected as subgroup A1, and the corresponding original thin-layer images selected as subgroup A2), single phase CTA examination was performed in group B, manual and AI image post-processing were performed respectively. Subjective scoring of the image data was performed, and the objective bid evaluation indexes such as CT value, noise (SD), signal-to-noise ratio (SNR), contrast to noise ratio (CNR) were measured, the qualified rate of artificial and AI vascular segmentation was counted, and post-processing time were recorded. The objective evaluation indexes were compared between three groups using one-way ANOVA, and the Kruskal-Wallis H test was used to compare the difference of subjective scores.Results:Statistically significant differences were observed in subjective score and objective evaluation index of original images among group A1, group A2 and group B (all P<0.05). Among them, arterial enhancement, arteriolar detail display score, cerebral artery CT value, SNR and CNR in group A1 were higher than those in group A2 and group B (all P<0.05). In a total of 100 patients with 1 100 blood vessels, the qualified rates of AI vascular segmentation in group A1 [98.4% (541/550)] and group B [98.7% (543/550)] were higher than those of manual [82.9% (456/550), 87.1% (479/550), χ2=77.392, 56.521, P<0.001], but the qualified rate of AI vascular segmentation of group A2 [78.4% (431/550)] was lower than that of manual [85.6% (471/550), χ2=9.855, P=0.002]. The completion time of AI post-processing were reduced by 56.30%, 49.63%, 50.81%, respectively than those with manual. Conclusion:Compared with manual image post-processing, AI has certain advantages in image quality and work efficiency of reconstructed CTA post-processing based on CTP de-noising dataset, and it is worth popularizing and applying in the image post-processing of cerebrovascular disease, combined with artificial quality control.

Objective: To investigate the feasibility of one-step coronary and carotid-cerebrovascular computed tomography angiography (CTA) using high-pitch Double Turbo Flash mode and to analyze the image quality and radiation dose in patients with heart rate variability using multi-slice detector dual-source CT. Methods: A total of 79 patients with heart rate variability higher than 3 beat/min (bpm) were retrospectively analyzed. They were grouped by the scanning methods. Group A (n=40) were performed double turbo flash mode for one-step coronary and carotid-cerebrovascular arteriesinjected with one injection of contrast agent.further divided into Single A (only the phase 1 image)and Double A(combined images of phases 1 and 2). Group B (n=39) were performed separately with twice injection of contrast agent. Subjective scoring was performed on the image quality of the group Single A, Double A and B using a 4-point. Then the objective parameters of image quality, CT attenuations, image noise, signal-to-noise (SNR), and contrast-to-noise (CNR), were evaluated. Then subjective scores, objective evaluation indicators, and radiation dose were compared with one-way ANOVA analysis among the three groups.Contrast agent were compared by using t test in group A and B. Results: No significant difference was found (F=2.093, P=0.128) for the subjective scores of the head and neck CTA among the three groups with (3.47±0.51), (3.53±0.51), (3.69±0.47). Significant difference was found (F=50.955, P<0.01) for the subjective scores of coronary CTA among the three groups with (2.70±0.76), (3.35±0.66), (3.58±0.50), and there was no statistically significant difference between Double A and B groups (P=0.104), met the requirements for diagnosis. The objective evaluation of the three groups compared the head and neck CTA images were statistically significant (P<0.05), of which the difference between the Single A and the Double A was not statistically significant (P>0.05), met the requirements for diagnosis; the differences in SNR and CNR of coronary CTA images are statistically significant (F=12.991, 12.236, P<0.01), and there was no statistically significant difference between Double A and B (P>0.05), met the requirements for diagnosis. Radiation dose in the group Double A was lower than group B (decreased by 46.15%,P<0.01).The amount of the contrast agent in the group Double A was lower than group B (decreased by 44.13%, t=-45.455;P<0.01). Conclusion The double turbo flash mode is feasibility for one-step coronary and carotid-cerebrovascular CTA in patients with the heart rate variability using multi-slice dual-source CT.This scan mode can maintain the diagnostic image quality with low contrast agent and radiation dose.

Objective To evaluate the feasibility and clinical efficacy of retroperitoneal laparoscopic adrenalectomy for the treatment of Cushing disease.Methods Clinical data collected from 38 cases retroperitonel laparoscopic adrenalectomy for Cushing disease,from February 2006 to February 2017 were analyzed retrospectively.Among them,there were 6 males and 32 females aged from 13 to 66 years old,with an average age of 38 years old.The disease history ranged from 2 to 96 months,with an average of 28.3 months.Besides,there were 32 cases that had previous history of transsphenoidal pituitary tumor surgery and or radiotherapy.All 38 cases underwent retroperitoneal laparoscopic adrenalectomy therapy.There were 8 cases accepted right adrenalectomy and left subtotal adrenalectomy at the same time,24 cases accepted unilateral adrenalectomy,another 6 cases of pituitary tumors without lesions in medical imaging underwent unilateral adrenalectomy.Results All operations were completed sucessfully without conversion to open surgery and mortality.There was no blood transfusion during the period of operation.The operation time ranged from 30 min to 270 min (mean 88.3 min),the amount of bleeding was among the range of 10 ml to 200 ml (mean 38.33 ml).During 2 to 13 years of the follow up (mean 7 years),the 24 h urine cortisol concentration in the first day after surgery of piatients with subtotal resection was 90.35-220.84 μg/24h (mean 102.83 μg/24h),and 6 cases were in the normal range.After surgery 6-11 months,the clinical symptoms completely disappeared.The hormone replacement therapy was discontinued 1-3 months after surgery.However,There were 3 cases treated with residual adrenalectomy because of the recurrence after 1,3.5,5.0 years respectively.30 cases underwent unilateral adrenalectomy,whose 24 h urine cortisol concentration in the first day after surgery was 99.80-550.84 μg/24h (mean 372.83 μg/24h),among which 24 cases were beyond normal range,and another 6 cases were within the normal range.Reviewing 24 h urine cortisol concentration one month later after operation,it was 382.16-520.34 μg/24h (mean 461.62 μg/24h),with the results of all cases being higher than the normal range,the clinical symptoms were not relieved satisfactorily.During 2 to 7 months after surgery,there were 22 cases further underwent contralateral subtotal adrenalectomy (80％),the remaining 8 cases underwent contralateral adrenalectomy and autologous transplantation of adrenal tissue.Immediately one day after surgery,the 24 h urine cortisol concentration level of patients was ranged from 62.58 to 182.34 μg/24h (mean 92.83 μg/24h),and all 22 cases were within the normal range.The clinical symptoms completely disappeared during next 6 to 9 months after surgery,and hormone replacement therapy was discontinued 3 months after surgery.There were 2 cases received residual adrenalectomy because of the recurrence.Lifelong hormone replacement therapy after surgery occurred in 13 cases and 5 cases developed Nelson syndrome.Conclusions Retroperitoneal laparoscopic of unilateral adrenalectomy and contralateral subtotal adrenalectomy for the treatment of Cushing disease was safe and effective.The contralateral adrenal subtotal resection could be performed at an appropriate time in the case of that the clinical symptoms not obvious.By doing so,it could significantly alleviate the clinical symptoms as well as avoiding lifelong hormone replacement therapy.Once recurrence,residual adrenalectomy can be considered.

Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies. In this study, we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n = 3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression, which included the following variables: male patients, induction chemotherapy for newly diagnosed or relapsed disease, neutropenia, neutropenia longer than 10 days, hypoalbuminemia, central-venous catheter, and history of IFD. The patients were classified into three groups, which had low (0-10, ~1.2%), intermediate (11-15, 6.4%), and high risk ( > 15, 17.5%) of IFD. In the validation set (n = 1389), the IFD incidences of the groups were ~1.4%, 5.0%, and 21.4%. In addition, we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients, whereas benefits were documented in intermediate (2.1% vs. 6.6%, P = 0.007) and high-risk patients (8.4% vs. 23.3%, P = 0.007). To make the risk score applicable for clinical settings, a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established, and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD. In conclusion, an objective, weighted risk score for IFD was developed, and it may be useful in guiding antifungal prophylaxis.