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 explore the relationship between the longitudinal change trajectory of white blood cell (WBC) and new-onset type 2 diabetes mellitus(T2DM).Methods:It was a prospective cohort study. A total of 2 792 people who underwent health examinations at the Health Management Center of the Affiliated Hospital of Qingdao University from January 2019 to December 2023 for five consecutive years and met the research standards were selected as the study subjects. Group-based trajectory modeling (GBTM) was established. The target population was divided into three groups based on the longitudinal change trajectory of WBC: low-stable group, medium-stable group and high-stable group. The cumulative incidence of T2DM in the three groups were analyzed. Multivariate Cox proportional risk regression models were used to analyze the correlation between different WBC trajectory groups and the risk of T2DM in total population, males and females. A restricted cubic spline regression (RCS) model was used to analyze the dose-response relationship between baseline WBC and risk of T2DM.Results:The cumulative incidence rate of T2DM in low-stable group, medium-stable group and high-stable group increased gradually, which was 2.5%, 5.3% and 6.9%, respectively ( χ2=19.024, P<0.001). After adjusting for multiple confounding factors in the Cox proportional hazards regression model, no significant difference in the incidence risk of T2DM among the three WBC trajectory groups in males; While the hazard ratios in the high-stable and medium-stable group in women was 2.852(95% CI: 1.067-7.628) and 2.588 (95% CI: 1.133-5.912), respectively, when compared with that in the low-stable group (both P<0.05). RCS curve analysis showed a linear relationship between WBC and the risk of T2DM in female ( Pnon-linear=0.956), when the WBC count was>5.53×10 9/L, the risk of T2DM increased with the rise of WBC. Conclusion:Higher WBC trajectory is positively correlated with the risk of new-onset T2DM in female health examination population.

Background: Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). Objectives: To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats.Method: Sixty male Sprague–Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing.Result: In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration.Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. Conclusions PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

AIM: To reveal that the targeted regulation of TGF-β1 by miR-21-5P is the key mechanism that mediates the activation of myocardial fibroblasts, and to clarify the intervention ofRadix Angelica Sinensis and Radix Hedysari ultrafiltration on the mechanism of miR-21-5P targeting to regulate TGF-β1 effect. METHODS: (1) The cells were randomly divided into normal group and irradiation group. The irradiation group received 6Gry single irradiation, and then RT-PCR was used to detect miR-21-5P, and Western Blot was used to detect the expression of α-SMA and TGF-β1. (2) The cells were randomly divided into normal group, irradiation group, miR-21-5P

Objective:To study the changing characteristics and impact factors of helical tomotherapy (HT)for longitudinal dose fall-off outside the target, in order to guide the plan junction or pretreatment target and implementation efficiency in clinical.Methods:Eight patients with head and neck tumors admitted to the Department of Oncology Radiotherapy of the First Affiliated Hospital of Zhengzhou University in December 2019 were retrospectively selected as the research objects. The planning target area and dose drop structure were outlined in the head and neck images with a thickness of 1 mm obtained by Siemens SOMATOM Definition AS positioning computerized tomography (CT). Different field widths (FW, 5.0 cm/2.5 cm/1.0 cm) and pitches (0.430/0.287/0.215) were assembled for planning with the same modulation factor (1.8), finest does calculation grid (0.195 cm ×0.195 cm) and other planning parameters were consistent. The plans were designed by different parameters, and the result was analyzed by univariate analysis.Results:The that different pitch curves coincided under the same field width by comparative analyzing, so pitchs had no effect on dose drop. The different field width curves were independent of each other, indicating that the field width had an effect on dose drop in the head and foot direction. The relationship between the longitudinal dose drop speed outside the target and the change of the field width was inversely correlated: the larger field widths meant the slower dose fall-off and the larger penumbra, while the smaller field widths meant the faster fall-off and the smaller penumbra. When the dose fall-off to 50% of the prescribed dose, the distance from the target was approximately equal to half the field widths, and the pitchs had not affect the rate of dose-drop, while the dose at different distances from the target boundary could be calculated by the fitting formulas. The field widths and pitchs had little effect on the CI and HI index of the target, relatively, the target area was best when the field width was 2.5 cm. The total beam-on time gradually decreased with the increase of the field widths and pitches.Conclusions:When segment target therapy needs to consider planning junction, execution efficiency, and controlling longitudinal dose fall-off and considered the execution, the optimal planned parameters such as field widths and pitches could be selected or the target at the junction regions could be adducted according to the longitudinal dose drop formula, so as to achieve the ideal dose distribution.

Objective:To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes.Methods:In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed.Results:The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant ( P>0.05) . The difference was not statistically significant ( P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment ( P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment ( P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group ( P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment ( P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment ( P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group ( P<0.05) . Conclusion:The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.

Objective:To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes.Methods:In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed.Results:The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant ( P>0.05) . The difference was not statistically significant ( P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment ( P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment ( P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group ( P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment ( P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment ( P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group ( P<0.05) . Conclusion:The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.

OBJECTIVE：To establish QAMS method for simultaneou s determination of 7 effective components in Yao medicine Yueli yaomi spray ，such as α-cyperone，α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide ， so as to provide method reference for the quality control of the preparation. METHODS ：GC method was adopted. The determination was performed on DB- 1701P capillary column ，using nitrogen as carrier gas. The temperature of the hydrogen flame ion detector was 240 ℃. The temperature was programmed ，the inlet temperature was 240 ℃，the injection volume was 1 μL and the split ratio was 20 ∶ 1. Using limonene as internal reference ，the relative correction factors of other 6 components were calculated，the contents of them were calculated with relative correction factors ，and then compared with the results of internal standard method （using naphthalene as internal standard ）. RESULTS ：The mass concentration linear range of α-cyperone， α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide were 0.008 9-1.110 0，0.028 3-3.540 0，0.020 5- 2.560 0，0.023 0-2.880 0，0.016 3-2.035 0，0.013 1-1.640 0，0.008 3-1.040 0 mg/mL（all r＞0.999 0）；the limits of quantification were 0.005 6，0.013 1，0.011 4，0.018 6，0.010 8，0.008 9，0.004 5 mg/mL；the detection limits were 0.001 9，0.004 1，0.003 7， 0.006 2，0.003 5，0.002 9，0.001 5 mg/mL；RSDs for precision ，stability（24 h），and repeatability tests were all less than 2％ （n＝5 or n＝6）； the average recoveries were 98.48％ ， 014） 101.37％，97.96％，99.80％，102.79％，97.77％，102.14％， and RSDs were all lower than 2％（n＝9），respectively. The average relative correction factors of α-cyperone，α-pinene， β-pinene，β-elemene，caryophyllene oxide and ligustilide were 1.045 8，0.621 0，0.488 5，0.382 9，0.708 9，0.956 9 respectively，and the RSDs were all lower than 2％（n＝6）. There wa s no statistical significance in contents of 7 components between QAMS method and internal standard method （P＞0.05）. CONCLUSIONS ：The established QAMS method is simple ， accurate，stable and reproducible ，and can be used for simultaneous determination for 7 components in Yueli yaomi spray.

Objective:To evaluate the multi-leaf collimator (MLC) performance of TrueBeam accelerator using trajectory log files.Methods:All tests were performed 5 times under different gantry-collimator angle combination. The 1 mm picket fences were constructed by static or dynamic MLC. The control ability for small-field accuracy of accelerator was evaluated. Repeatability was assessed by MLC repeat motion. The movement performance of difference velocities along one direction and the opposite direction were evaluated via a 1 cm picket fences which slipped from -7 cm to 7 cm with a uniform velocity and stopped or immediately back at 7 cm. The MLC performance in a complex program was evaluated by a cross movement test.Results:Both the static and the dynamic picket fences yielded high accuracy. The deviation spectrums of MLC in different gantry angle were consistent, however, an absolute difference of 0.001 1 mm was found. For uniform velocity movement tests with 0°gantry, the RMSE of MLC was increased from 0.015 0 mm to 0.059 8 mm when the speed was accelerated from 5 mm/s to 25 mm/s. Similar results were obtained in non-zero gantry angle. The "overspeed" effect caused by the direction change movement of MLC was less obvious than that caused by speed changed from zero to a uniform velocity movement state. There was no significant change in speed before and after the MLC crossing. The MLC speed fluctuated around the set value, which was independent of the gantry angle.Conclusion:A method for evaluating the performance of MLC using trajectory log files is established, which can evaluate the MLC performance of TrueBeam accelerator and be used for MLC rapid quality control in clinical practice.