Drug clinical trials constitute a critical link in new drug development and an essential means to verify the safety and efficacy of pharmaceuticals. The protection of participants’ rights and interests and the prevention of risks directly affect the scientific ethics and social credibility of the trials. Vulnerable groups， due to restricted autonomous decision-making capacities or special social status， are more susceptible to safety risks. Children are a typical representative of vulnerable groups. Their physiological particularities， cognitive limitations， and dependence collectively epitomize the universal protection demands of vulnerable research participants. Taking children as an instance， this paper analyzes the current weak links in the protection of pediatric research participants. Integrating advanced international experience with domestic practical demands， it comprehensively identified protection risk points at every stage and constructed a multi-stakeholder collaborative mechanism for the full-process protection of pediatric research participants. This mechanism incorporated seven main entities， including drug regulatory authorities， sponsors， researchers， and ethics committees， covering the pre-trial， intra-trial， and post-trial phases to meet the requirements of full-chain and multi-dimensional protection. It provided references for the subsequent establishment of a systematic protection mechanism for vulnerable populations.

Objective:To investigate impact of baicalein(BA)on airway inflammation in chronic obstructive pulmonary disease(COPD)rats by regulating TLR4/NF-κB pathway.Methods:Rats were randomly divided into model group(n=56)and sham operation group(n=10),COPD rat model was established by smoking and intratracheal instillation of LPS,successful modeling rats were randomly divided into COPD group,BA low dose(BA-L,100 mg/kg)group,BA high dose(BA-H,200 mg/kg)group,TLR4 activator LPS group(0.1 mg/kg)and BA-H+LPS group(0.1 mg/kg LPS+200 mg/kg BA).After 2 h,peak expiratory flow(PEF),forced expiratory volume in first second(FEV1),forced vital capacity(FVC)and other lung function indexes were measured;serum TNF-α,IL-6 and IL-8 levels were measured;bronchoalveolar lavage fluid(BALF)was collected to analyze number and classification of cells;lung tissues were isolated to analyze pathological changes and TLR4,p-NF-κB p65/NF-κB p65 expressions.Results:Com-pared with sham operation group,pathological damage in COPD group was serious,PEF,FEV1 and FVC were decreased significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lymphocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were increased significantly(P<0.05);compared with COPD group,pathological damage in LPS group was further aggra-vated,PEF,FEV1 and FVC were reduced significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lym-phocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were increased significantly(P<0.05),pathological damage in BA-L group and BA-H group gradually improved,PEF,FEV1 and FVC were increased significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lymphocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were decreased significantly(P<0.05);LPS reversed protective effect of BA-H on COPD rats.Conclusion:BA can improve airway inflammation in COPD rats,which may be related to inhibition of TLR4/NF-κB pathway.

Objective:To investigate impact of baicalein(BA)on airway inflammation in chronic obstructive pulmonary disease(COPD)rats by regulating TLR4/NF-κB pathway.Methods:Rats were randomly divided into model group(n=56)and sham operation group(n=10),COPD rat model was established by smoking and intratracheal instillation of LPS,successful modeling rats were randomly divided into COPD group,BA low dose(BA-L,100 mg/kg)group,BA high dose(BA-H,200 mg/kg)group,TLR4 activator LPS group(0.1 mg/kg)and BA-H+LPS group(0.1 mg/kg LPS+200 mg/kg BA).After 2 h,peak expiratory flow(PEF),forced expiratory volume in first second(FEV1),forced vital capacity(FVC)and other lung function indexes were measured;serum TNF-α,IL-6 and IL-8 levels were measured;bronchoalveolar lavage fluid(BALF)was collected to analyze number and classification of cells;lung tissues were isolated to analyze pathological changes and TLR4,p-NF-κB p65/NF-κB p65 expressions.Results:Com-pared with sham operation group,pathological damage in COPD group was serious,PEF,FEV1 and FVC were decreased significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lymphocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were increased significantly(P<0.05);compared with COPD group,pathological damage in LPS group was further aggra-vated,PEF,FEV1 and FVC were reduced significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lym-phocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were increased significantly(P<0.05),pathological damage in BA-L group and BA-H group gradually improved,PEF,FEV1 and FVC were increased significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lymphocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were decreased significantly(P<0.05);LPS reversed protective effect of BA-H on COPD rats.Conclusion:BA can improve airway inflammation in COPD rats,which may be related to inhibition of TLR4/NF-κB pathway.

Objective:To analyze the risk factors for frailty in older adult patients with chronic obstructive pulmonary disease (COPD) and its correlation with oxidative stress.Methods:A total of 168 patients with COPD aged 60 years and above, who were treated at Pingxiang People's Hospital from August 2022 to August 2023, were selected as the study subjects using the convenient sampling method. The FRAIL scale was utilized to assess frailty status. Patients were divided into two groups based on their FRAIL scale scores: the frail group (≥ 3 points, n = 109), the non-frail/pre-frail group (< 3 points, n = 59). Patients in the non-frail/pre-frail group were sub-divided into the pre-frail group (1-2 points, n = 23), and the non-frail group (0 points, n = 36). Serum levels of 8-hydroxydeoxyguanosine and malondialdehyde, and total antioxidant capacity were measured. One-way analysis of variance was performed to compare differences between groups, and correlation analysis was conducted. Logistic regression was used to identify the risk factors for frailty. Results:The incidence of frailty among 168 older adult patients with COPD was 64.9% (109/168). Multivariable logistic regression analysis revealed that age ( OR = 1.59, 95% CI 1.02-2.25), body mass index ( OR = 4.11, 95% CI 2.02-8.42), comorbidities ( OR = 2.57, 95% CI 1.31-5.02), activities of daily living ( OR = 3.07, 95% CI 1.54-6.06), malnutrition ( OR = 2.97, 95% CI 1.56-5.41), and cognitive impairment ( OR = 2.87, 95% CI 1.42-5.88) were risk factors for frailty in older patients with COPD ( P < 0.05). The frailty scores of older adult patients with COPD were significantly positively correlated with serum levels of 8-hydroxydeoxyguanosine and malondialdehyde ( γ= 0.67, 0.65, P = 0.008, 0.006), and negatively correlated with total antioxidant capacity ( γ= -0.54, P = 0.012). Conclusion:Age, body mass index, comorbidities, activities of daily living, malnutrition, and cognitive impairment are risk factors for frailty in older adult patients with COPD, and the severity of frailty is markedly associated with levels of oxidative stress products.

Objective:To investigate the correlation between exhaled nitric oxide and obstructive sleep apnea-hypopnea syndrome (OSAHS).Methods:Eighty patients with OSAHS (OSAHS group) who received treatment in Pingxiang People's Hospital from September 2019 to September 2021 were included in this study. An additional 60 patients with snoring (snoring group) who concurrently received treatment in the same hospital were included in the control group. The value of exhaled nitric oxide was measured using an exhaled nitric oxide detector. The relationship between exhaled nitric oxide and apnea-hypopnea index, and the lowest oxygen saturation level during sleep (LSaO 2) was analyzed using Pearson correlation analysis. The optimal cut-off value of exhaled nitric oxide for predicting OSAHS was analyzed using the receiver operating characteristic curve. Results:Exhaled nitric oxide and apnea-hypopnea index in the OSAHS group were (18.61 ± 6.23) μg/L and (44.50 ± 16.15) times/hour, respectively, which were significantly greater than (11.17 ± 4.31) μg/L and (2.91 ± 0.79) times/hour in the snoring group ( t = 7.94, 14.08, both P < 0.05). LSaO 2 in the OSAHS group was significantly lower than that in the snoring group [(66.53 ± 10.17)% vs. (92.15 ± 1.62)%, t = -13.61, P < 0.05]. Correlation analysis showed that exhaled nitric oxide levels in patients with OSAHS were positively correlated with apnea-hyponea index ( r = 0.56, P = 0.001), and negatively correlated with the lowest oxygen saturation level ( r = -0.54, P = 0.002). The receiver operating characteristic curve analysis revealed that when the optimal cut-off value of exhaled nitric oxide was 11.5 μg/L, the area under the curve was 0.846, with sensitivity of 91.3%, and specificity of 63.3%. Conclusion:Patients with OSAHS have airway inflammatory reactions. The level of nitric oxide in exhaled air is positively correlated with the severity of OSAHS, which has a certain clinical value.

Objective     To investigate short-term outcomes of robot-assisted Heller-Dor myotomy (RAHM-Dor) for achalasia of cardia and our learning curve experience. Methods     The clinical data and recent follow-up results of 42 patients who received RAHM-Dor from November 2015 to January 2020 in the Department of Thoracic Surgery of the First Affiliated Hospital of Nanchang University were retrospectively analyzed, including 20 males and 22 females with a mean age of 40.8±18.4 years. Results    Dysphagia was the most common symptom, followed by heartburn and regurgitation. The mean operation time was 122.8±23.9 min. The mean blood loss was 47.5±32.7 mL. Two patients suffered mucosal injury, and successfully repaired by suturing during surgery. There was no esophageal fistula, conversion to an open operation or perioperative death in this series. The median length of hospital stay was 8 (6, 9) d. In all patients, the Stooler and Eckardt scores of postoperative 1, 6 and 12 months decreased compared to those of pre-operation (P<0.001). Conclusion     RAHM-Dor is a safe and feasible avenue for the treatment of achalasia of cardia, and can achieve a satisfying short-term results. The learning curve shows a transition to the standard stage from the learning stage after 16-18 operations.

Objective:By comparing the changes of metabolic parameters before and after laparoscopic sleeve gastectomy (LSG) in patients with type 2 diabetes mellitus (T2DM) and obesity, the insulin resistance index (HOMA-IR) and atherogenic index of plasma (AIP) were calculated to evaluate the effect of metabolic surgery on insulin resistance and atherosclerosis in patients with type 2 diabetes mellitus (T2DM) and obesity.Methods:LSG treatment were retrospectively analyzed in 54 patients with type 2 diabetes mellitus and obesity, detection of preoperative and postoperative 1 month, 6 month of fasting plasma glucose (FPG), fasting insulin (FINS), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), measuring blood pressure, body weight, calculating body mass index, and according to the steady state evaluation model and the formula for calculating HOMA-IR and AIP. Before and after surgery, paired t test was used, and Pearson correlation analysis and multiple stepwise regression analysis.Results:FPG, FINS, TG, HOMA-IR and AIP were (6.38±2.03) mmol/L and (5.36±1.33) mmol/L, (20.42±25.77) uU/mLand (11.22±3.62) uU/mL, (1.94±2.81) mmol/Land (1.70±2.33) mmol/L, (5.60±7.52) and (2.58±0.80), (0.15±0.27) and (0.08±0.25) ,which were significantly lower than those before surgery ( P<0.05) ,HDL-C was (1.04±0.20) mmol/L and (1.10±0.18) mmol/L at 1 and 6 months after operation, respectively, which was higher than that before operation ( P<0.05) .Preoperative correlation analysis showed that AIP was positively correlated with FPG, TG and HOMA-IR ( P<0.05), and negatively correlated with HDL-C ( P<0.05) .The results of multiple stepwise regression analysis showed that FPG, TG and HDL-C were independent influencing factors of AIP ( P<0.05) . Conclusion:LSG surgery can effectively reduce the blood glucose and lipid levels in patients with type 2 diabetes complicated with obesity, improve insulin resistance and reduce the plasma atherosclerosis index.

Objective: To explore the effect of pulsatile lavage on wound healing in diabetic foot ulcer patients. Methods: The random number table method was used to divide 86 patients of diabetic foot ulcers into two groups with 43 patients in each group. The control group disinfected and cleaned the wound by routine methods, while the experimental group received closed pulse irrigation with sewage collection unit. The two groups were debridement, dressing selection and wound dressing in a unified way. The frequency of dressing change, time of dressing change, efficacy, cost of dressing changes, score of wound pain and wound healing were observed. Results: The frequency of dressing change, dressing change time, wound healing time and total effective rate of the experimental group were (10.42±1.92) times, (12.19±2.37) min, (32.53±6.91) d and 86.04% (37/43), respectively, while those of the control group were (19.47±3.13) times, (21.65±3.99) min, (43.17±13.72) d and 51.16% (22/43), with statistically significant differences (t values were 4.545-16.127, χ² value was 13.214, all P < 0.01). However, the cost of dressing change in the experimental group was (3 278.78±220.92) yuan, and that in the control group was (3 195.75±206.54) yuan. There was no significant difference between the two groups (t value was -1.814, P > 0.05). The pain scores were (1.47±1.09), (0.57±0.72), (0.06±0.23), (0.003±0.01) points in the experimental group at the 2nd week,the 4th week,the 6th week and the 8th week after intervention, and they were (3.83±1.16), (2.73±1.41), (1.92±1.06), (1.43±0.70) points respectively in the control group, the differences were statistically significant (F_time=390.663, F_intergroup=76.011, F_interaction=4.210, all P < 0.01). The wound healing rates were (49.34±9.34)%, (86.26±13.33)%, (95.01±8.56)%, (97.28±3.62)% respectively in the experimental group in the 2nd week,the 4th week,the 6th week and the 8th week after intervention,while in the control group they were (26.64±5.19)%, (50.37±10.53)%, (64.84±12.27)% and (72.04±12.96)%. The differences between the two groups were statistically significant (F_time=354.487, F_intergroup= 921.230, F_interaction =23.154, all P < 0.01). Conclusions Pulsatile lavage can effectively clean the wound, reduce the frequency of dressing change, shorten the time of dressing change and wound healing, reduce the wound pain, improve the wound healing rate of diabetic foot ulcers, and did not increase the economic burden of patients, which was worthy of clinical application.

Objective:To establish the ultrasonic classification criteria of adhesive intestinal obstruction (AIO) and to discuss its clinical value.Methods:The data of 124 cases of AIO confirmed by surgery and pathology in Tianjin Nankai Hospital from January 2014 to October 2019 were retrospectively analyzed. The ultrasonic image features of AIO were summarized. According to the severity of ultrasound images it can be divided into three different types: simple (mild) AIO, complex (moderate) AIO and critical (severe) AIO. The surgery plan was simulated according to the ultrasonic classification results and compared with the actual surgery results.Results:①The ultrasonic classification results of 124 cases of AIO were as follows: simple (mild) AIO in 73 cases (58.9%), complex (moderate) AIO in 16 cases (12.9%), critical (severe) AIO in 35 cases (28.2%). ②The characteristic ultrasonic images of simple (mild) AIO were adhesion of the intestinal wall to the intestinal wall and the intestinal wall to the abdominal wall; the characteristic ultrasonic images of complex (moderate) AIO were adhesive band and adhesive mass; the characteristic ultrasonic images of critical (severe) AIO were internal hernia, volvulus, intussusception, intestinal ischemia and necrosis, and bloody ascites. ③According to the results of ultrasound classification, 124 cases of AIO were treated with simulated surgical procedures, and the coincidence rate with the surgical results was high (87.9%).Conclusions:US classification of AIO is helpful for clinical evaluation of the severity of AIO and can provide imaging basis for clinicians to make the correct treatment plan.

Objective: To explore the changes and clinical significance of serum prolactin and estrogen levels in women with autoimmune thyroid diseases. Methods: From January 2018 to December 2018, 76 newly diagnosed female patients with autoimmune thyroid diseasein outpatient and inpatient clinics of the People's Hospital of Hebei Province were selected as study group, including 40 cases of Graves' disease and 36 cases of hashimoto's thyroiditis.And 60 healthy women with age matched were selected as control group.Serum estrogen, prolactin, thyroid hormone and their antibodies, IL-2, IL-6, IL-10 and other related indicators were determined before and after treatment, and the correlation analysis was performed. Results: The levels of estrogen[(302.85±78.62)ng/L], prolactin [(15.98±4.18)μg/L], IL-2 [(224.45±61.28)ng/L], IL-6 [(211.46±67.25)ng/L] in the study group were all higher than those in the control group [(228.4±71.38)ng/L, (10.35±3.21)μg/L, (120.34±38.27)ng/L, (165.51±50.09)ng/L], and the IL-10 level in the study group was lower than that in the control group [study group: (15.65±4.86)ng/L; control group: (20.12±4.83)ng/L] , there were statistically significant difference between the two groups(t=5.78, 3.11, 8.98, 3.94, all P<0.05). After treatment, the levels of estrogen [(237.11±70.42)ng/L], prolactin[(10.40±3.32)μg/L], IL-2[(122.67±38.99)ng/L], IL-6[(166.24±52.09)ng/L] in the study group were significantly decreased compared with before treatment(t=5.56, 3.76, 9.04, 4.02, all P<0.05), and the IL-10 level [(19.96±4.93)ng/L] was significantly increased (t=3.95, P<0.05). However, there was no statistically significant difference in thyroid antibody between the two groups (P>0.05). Estrogen level was positively correlated with prolactin, IL-2 and IL-6(r=0.327, 0.298, 0.336, all P<0.01), and negatively correlated with IL-10(r=-0.285, P<0.05). Conclusion Elevated levels of estrogen and prolactin can stimulate the production and release of inflammatory cytokines, thus affecting the level of thyroid hormone, which is closely related to the female autoimmune thyroid disease.