Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Objective:To investigate the protective effects of a sunscreen lotion containing Calendula extracts on children′s skin against sun exposure, as well as to evaluate its safety and tolerability when applied to children.Methods:A single-center, randomized, split-body/face study was conducted on 200 healthy children aged 3 - < 18 years, who were enrolled from Beijing Children′s Hospital, Capital Medical University from July to August 2022. The participants were randomly and equally divided into Group A (the left side of the body/face topically treated with the test sunscreen, and the right side with the control sunscreen) and Group B (the right side of the body/face topically treated with the test sunscreen, and the left side with the control sunscreen) at a ratio of 1∶1. After applying the sunscreen, they were engaged in outdoor activities under sunlight. Skin tests were conducted on the temporal area, the extensor aspect of the upper arm and forearm before and after sun exposure. The test product was a mild sunscreen lotion containing Calendula extracts with the sun protection factor (SPF) being 50+ and the long-wave ultraviolet protection factor (PA) being +++, and the control product was a baby sunscreen containing licorice extracts (SPF35, PA++). Bilateral differential scales were used to assess clinical symptoms after sun exposure, erythema values to clinically evaluate erythema after sun exposure, and the multifunctional skin testing platform MPA10 to measure melanin and erythema values, stratum corneum hydration, and transepidermal water loss (TEWL) at the tested sites. Related adverse events were observed and recorded during the study. The paired t-test or Wilcoxon signed-rank test was used for the comparison of quantitative data, and chi-square test (Fisher′s exact test) for the comparison of count data. Results:Totally, 198 children completed the study and visits, including 100 males (50.5%) and 98 females (49.5%), aged from 3 to 17 years (8.11 ± 0.23 years), and there were 99 cases each in the Group A and Group B. The numbers of participants with more obvious sunburn symptoms after sun exposure in the 3 tested areas were all higher on the control side than on the test side (the temporal area: 11 cases vs. 4 cases; the extensor aspect of the upper arm: 16 cases vs. 2 cases; the extensor aspect of the forearm: 33 cases vs. 3 cases), with significant differences between the bilateral sides (all P<0.001). No significant differences were observed in the erythema values between the test side and control side in the 3 tested areas (all P > 0.05). In the extensor aspect of the upper arm and forearm, the difference in the melanin value before and after sun exposure was significantly smaller on the test side (3.57 ± 2.41, 1.74 ± 1.68, respectively) than on the control side (9.50 ± 2.21, 8.13 ± 1.87, respectively, both P < 0.001) ; in the temporal region and the extensor aspect of the upper arm and forearm, the difference in the stratum corneum hydration level before and after sun exposure was significantly greater on the test side (7.72[-2.19, 19.44], 9.56 ± 1.37, 9.05 ± 1.37, respectively) than on the control side (-3.25[-13.54, 9.94], 3.63 ± 1.32, 3.73 ± 1.31, respectively, all P < 0.001) in the temporal region and the extensor aspect of the upper arm and forearm. However, there were no significant differences in the changes in the erythema or TEWL values before and after sun exposure between the test side and control side in either of the 3 tested areas (all P > 0.05). During this study, 1 case (0.51%) experienced transient urticaria on the control side, and no serious adverse events occurred. Conclusion:The mild sunscreen lotion containing Calendula extracts demonstrated superior efficacy to the control product in improving skin symptoms after sun exposure such as hyperpigmentation among healthy children aged 3 - < 18 years, with good tolerability and a relatively low incidence of adverse reactions.

Objective:To evaluate the efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis (AD) in children during the maintenance period.Methods:A randomized, blank-controlled, multicenter clinical study was conducted in children with moderate AD from Beijing Children′s Hospital, Capital Medical University, Children′s Hospital of Chongqing Medical University and Shenzhen Children′s Hospital from March 2021 to February 2022. A total of 127 children aged 0 - 12 years with moderate AD were treated with topical glucocorticoids combined with emollients during the run-in period, 112 out of them achieved the investigator′s global assessment (IGA) score ≤ 1 point, and then the 112 patients were randomly divided into a test group (56 cases) and a control group (56 cases) at a ratio of 1∶1. Patients in the test group received treatment with a test emollient twice a day in combination with topical glucocorticoids applied at the weekend, and those in the control group were only treated with topical glucocorticoids at the weekend. Patients in the two groups were followed up at baseline, week 2 (± 3 d), week 4 (± 5 d), and week 12 (±7 d), as well as at the time of AD relapse, and the effect of the test emollient on the remission rate of AD in children during the maintenance period was evaluated, so were its effects on the dosage of topical glucocorticoids, pruritus, sleep, and skin pH. The occurrence of treatment-related adverse events was evaluated and recorded at the same time. Study endpoints were defined as AD relapse during the maintenance period, end of 12-week follow-up, or occurrence of serious adverse events. Comparisons of efficacy indicators between groups were conducted by using chi-square test, Kaplan-Meier survival analysis, Satterthwaite t′ test and Mann-Whitney U test. Results:In the full-analysis set, 45 (80.36%) patients with AD maintained remission in the test group (56 cases) and 30 (53.57%) in the control group (56 cases), and the remission rate difference between the two groups was 26.79% (95% confidence interval [ CI]: 10.09%, 43.49%; χ2 = 9.11, P = 0.003) ; the 12-week follow-up during the maintenance period showed that the time to first relapse was 75.05 ± 25.07 days in the test group, which was significantly longer than that in the control group (49.55 ± 33.92 days, t′ = 4.52, P < 0.001). At the study endpoint, the test group showed significantly decreased AD disease severity score (eczema area and severity index [EASI] score: 0.00 [0.00, 1.20] points vs. 0.60 [0.00, 4.00] points), pruritus visual analog scale (VAS) score (0.00 [0.00, 2.00] points vs. 2. 00 [0.00, 10.00] points), and sleep VAS score (0.00 [0.00, 0.00] points vs. 1.00 [0.00, 4.00] points) compared with the control group ( Z = -2.77, 2.43, 3.48, P = 0.006, = 0.015, < 0.001, respectively), while there was no significant difference in the pH value at the lesional sites between the test group and control group ( t = 0.97, P = 0.335). For the group aged 0 - 2 years, the average daily glucocorticoid dosage at the weekend in AD children during the maintenance period was significantly lower in the test group than in the control group ( Z = -1.97, P = 0.049) ; for the group aged >2 - 12 years, there was no significant difference in the average daily glucocorticoid dosage at the weekend between the two groups ( Z = -0.25, P = 0.802). During the study period, no significant difference was observed in the incidence of treatment-related adverse events between the test group (2/56, 3.57%) and control group (3/56, 5.36%; P = 1.000), and no serious adverse events occurred. Conclusion:Compared with the weekend treatment with topical glucocorticoids alone, the daily use of the test emollient combined with topical glucocorticoids at the weekend could markedly improve the remission rate of AD, prolong the time to relapse, and reduce the disease severity at relapse in children with AD during the maintenance period, which provides a new option for maintenance treatment of children with AD.

Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Objective:To investigate short-term efficacy and safety of subcutaneous injection of dupilumab in the treatment of moderate-to-severe childhood atopic dermatitis (AD) .Methods:A retrospective study was conducted on clinical data from children who were diagnosed with moderate-to-severe AD and subcutaneously injected with dupilumab in Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from March 2021 to August 2021. Changes in the Eczema Area and Severity Index (EASI), itch Numeric Rating Scale (NRS) score, SCORing Atopic Dermatitis (SCORAD) index, and Dermatology Family quality of life Index (DFI) were analyzed before and 4 weeks after the first subcutaneous injection of dupilumab. Adverse events were collected during the first injection to the first follow-up visit at week 4 after the start of treatment. Normally distributed measurement indices were compared by using paired t test, non-normally distributed measurement indices were compared by using signed rank test, and logistic regression analysis was used to evaluate the effects of disease duration, eosinophil counts, IgE levels, personal and family history of allergic diseases on EASI50 (≥ 50% decrease in the EASI score) after dupilumab treatment. Results:A total of 39 children were enrolled in this study, including 21 males and 18 females. Twenty-one patients were aged 2 to < 6 years, 18 were aged 6 to < 18 years, and their median age ( Q1, Q3) was 65.0 (53.0, 111.0) months. Four weeks after the single-dose subcutaneous injection of dupilumab, 18 patients (84.85%) achieved ≥ 50% decrease in EASI score, 13 (60.61%) ≥ 75% decrease in EASI score; 18 (75.76%) experienced a decrease of ≥ 4 points in peak NRS, and 20 (81.82%) ≥ 3 points in peak NRS; the SCORAD score decreased by ≥ 50% in 15 (68.75%) patients, and by ≥ 75% in 7 (18.75%). Neither common adverse events such as conjunctivitis, skin infections, injection site reactions, nor serious adverse events were observed in any of the children from the first injection to the first follow-up visit at week 4. Logistic regression analysis showed no significant effect of the disease duration, eosinophil counts, IgE levels, personal or family history of allergic diseases on EASI50 (all P > 0.05) . Conclusion:A single-dose subcutaneous injection of dupilumab can markedly improve pruritus and severity of skin lesions in children with moderate-to-severe AD, and enhance the family quality of life, with favorable short-term safety.

BACKGROUND: This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis. METHODS: First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system. RESULTS: A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011). CONCLUSION The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics* ; Silicosis/genetics*

Objective: To investigate the effects of parental feeding practices on anemia in children aged 0-6 years in the minority area of the plateau, and to provide evidence for anemia intervention. Methods: A total of 1 726 children aged 0-6 years in 4 counties of Gannan Tibetan Autonomous Prefecture were selected by stratified random cluster sampling to measure hemoglobin level. Parental feeding practices were evaluated. Results: The anemia prevalence rate among children aged 0-6 years was 50.3%. The prevalence of anemia was higher in those with younger age, Tibetan ethnic, rural residence, low parents education level and family income(χ2=156.95，899.51，148.17，8.18，16.36，11.03，P<0.05). Parentl awareness rates on feeding knowledge were 10.0%-53.7%. The report rates of distraction and force-feeding were 51.4% and 36.1%, respectively. Logistic regression analysis showed that parents incorrect feeding knowledge and compulsive feeding behaviors were positively associated with anemia in children(P<0.05). Conclusion Improvement of parents health literacy and feeding behavior is an important intervention to reduce anemia in children aged 0-6 years.

We reported a clinical caseof gas gangrene in the lower back and buttocks due to local intramuscular injection. A 43-year-old male was treated by local private clinic for low back pain. He underwent local intramuscular injection in his lower back and buttocks. 5 or 6 hours after the treatment,he felt worsen of low back pain (VAS 5 points)with a fever. After one day of treatment, the lower back pain was even worse(VAS 8 points). And he had soy-sauce urine and a high fever. The results of laboratory examination and clinical manifestation suggested multiple organ failure within a short period of time. Imaging (CT) suggested large area of gas and muscle necrosis in the lower back and buttocks. Considering the progress of the disease, emergency surgery on lumbar back and right buttocks was performed after hospitalization. Rapid bacterial smear reported gram-positive coarse bacteria. Anaerobic culture suggested clostridium perfringens. Aerobic culture result did not show any bacterial growth. According to the clinical manifestation, imaging (CT), intraoperative judgment and postoperative anaerobic culture results, the clinical diagnosis was gas gangrene. Gas gangrene is a special infectious disease in clinic, which can be characterized by low morbidity, difficult early diagnosis,rapid disease progression and high mortality. Sinceintramuscular injection leaded to this disease in our case, the importance of standardized aseptic procedures should be emphasized.

OBJECTIVE: To explore the effect of occupational lead exposure on the relative telomere length(RTL) and mRNA expression of telomere-binding protein POT1-interacting protein 1(TPP1) in peripheral blood of workers. METHODS: A total of 303 workers exposed to lead were selected as the exposure group and 72 administrative logisticians personnel in the same factory as the control group using the simple random sampling method. Their peripheral blood samples were collected and were used to detect the blood lead level by Graphite furnace atomic absorption spectrometry. RTL and the relative expression of TPP1 mRNA by real-time quantitative polymerase chain reaction. RESULTS: The blood lead level of the exposure group was higher [Media(M): 68.2 vs 266.1 μg/L, P<0.01], the RTL was shorter(M: 0.96 vs 0.70, P<0.01), and the relative mRNA expression of TPP1 was lower(M: 0.92 vs 0.51, P<0.01) compared with the control group. Spearman correlation analysis results showed that the blood lead level were both negatively correlated with RTL [Spearman correlation coefficient(r_S) =-0.18, P<0.01], and the relative mRNA expression of TPP1(r_S=-0.19, P<0.01), while the RTL was positively correlated with the risk of RTL shortening and the relative mRNA expression of TPP1 decline was increased in lead exposure(P<0.01). CONCLUSION: Lead exposure can shorten the RTL and reduce the relative mRNA expression of TPP1 in workers. The mechanism may be that lead interferes with telomere repair process by inhibiting the mRNA expression of TPP1.

Objective:To investigate the detection of suspected occupational diseases in the occupational health examination population in Hangzhou, and to establish a two-level logistic model of influencing factors.Methods:In October 2018, the information of physical examinees was collected through the 2015-2017 occupational health examination and reexamination database of Hangzhou Hospital for the Prevention and Treatment of Occupational Disease. MlwiN 2.02 software was used to establish a 2-level logistic model of suspected occupational diseases, with the occupational hazard factors as the level 2 unit and the employees as the level 1 unit. χ 2 test was used to compare the detection rates of suspected occupational diseases with different characteristics. The trend of detection rates of suspected occupational diseases with age and working age were tested by Cochran-Armitage trend test. Results:The morbidity rate of suspected occupational diseases in 2965 workers was 59.6% (1767/2965) , and the rates caused by different occupational hazardous factors were significantly difference (χ 2=1615.27, P<0.01) , that caused by noises was the highest (98.0%, 1206/1231) , and the next was the dust (87.5%, 70/80) . The rate in male was 61.5% (1532/2492) , and that in female was 49.7% (235/473) , they were significantly difference (χ 2=22.96, P<0.01) . The rates of suspected occupational diseases increased with the ages ( Z=8.77, P<0.01) and working years ( Z=3.62, P<0.01) . The multivariate analysis by 2-level logistic model indicated that gender, age and working year were all no significant, instead the level 2 unit random effect was significant (χ 2=4.77, P<0.05) . Conclusion:Suspected occupational diseases will occur in clusters in occupational hazardous factors. The influence of occupational hazardous factors on suspected occupational diseases was more than that of personal characteristics.