ObjectiveThe effects of two microbial fertilizers （Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer） on the growth and development， the accumulation of active ingredients， and the microbial community diversity of rhizosphere soil of Atractylodes chinensis were investigated. MethodsA field experiment was carried out with two-year-old Atractylodes chinensis as the test material. Plant samples were collected during the wilt stage （September 26， 2023） to determine the general agronomic traits of Atractylodes chinensis. High-performance liquid chromatography （HPLC） was utilized to evaluate the effects of microbial fertilizers on the synthesis and accumulation of four active ingredients （atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ） in Atractylodes chinensi. PacBio Sequel sequencing technology was used to explore the differences in bacterial community structures and diversity in the rhizosphere soil of Atractylodes chinensis treated with different microbial fertilizers. ResultsThe two microbial fertilizers had significant growth-promoting effects on Atractylodes chinensis. Compared with those of the CK group， the stem diameter， stem and leaf dry and fresh weight， and rhizome dry and fresh weight of Atractylodes chinensis significantly increased by 0.47-1.07 times （P<0.05） after the application of the Bacillus subtilis fertilizer （16 kg/667 m²）， and those significantly increased by 0.62-0.96 times （P<0.05） after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer （1.5 kg/667 m²）. The effect on plant height was not significant. The application of two microbial fertilizers was beneficial to the accumulation of atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ （P<0.01）， and the effect of the Bacillus subtilis fertilizer on the accumulation of active ingredients of Atractylodes chinensis was better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The results of high-throughput sequencing showed that compared with the CK group， the Bacillus subtilis fertilizer （8 kg/667 m²） could significantly increase the diversity of rhizosphere bacterial species by regulating the Simpson index and Shannon index （P<0.05）， and the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer significantly reduced the bacterial diversity （P<0.05）. The relative abundance of dominant bacteria was compared at the phylum and genus levels. The relative abundance of Proteobacteria （45.73%） and Burkholderia_Caballeronia_Paraburkholderia （9.98%） significantly increased after the application of the Bacillus subtilis fertilizer （P<0.01）， and the relative abundance of Acidobacteriota （20.53%） and Sphingomonas （3.63%） increased significantly （P<0.01） after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The relative abundance of beneficial bacteria in the Bacillus subtilis fertilizer was slightly higher than that in the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. Pearson correlation analysis showed that Burkholderia_Caballeronia_Paraburkholderia and Sphingomonas were positively correlated with the content of atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ （P<0.05）. ConclusionThe application of the Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer can increase the yield of medicinal materials and promote the synthesis and accumulation of active ingredients by regulating the rhizosphere microecological diversity of Atractylodes chinensis， and the application effect of the Bacillus subtilis fertilizer is better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer.

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 vaccination status and vaccination willingness of novel coronavirus in HIV/AIDS population in Yunnan.Methods From October 2021 to June 2022,a questionnaire survey was conducted among 2180 HIV/AIDS patients in Kunming,Qujing,Yuxi,Zhaotong,Puer,Baoshan,Lincang,Honghe,Wenshan,Xishuangbanna,Dali,Dehong and Nujiang prefectures.The questionnaire included age,sex,education,nationality,education level,vaccination,adverse reactions within 7 days after the vaccination,safety of COVID-19 vaccine,awareness of effectiveness,vaccination willingness and so on.Results Among the subjects,2109 completed 3 injections,accounting for 96.74%,and 71 were not vaccinated,accounting for 3.26% .Within 7 days of inoculation,local adverse reactions occurred in 116 cases,accounting for 5.50%,and systemic adverse reactions occurred in 56 cases,accounting for 2.66% .Injection site pain,fatigue and muscle pain accounted for the highest proportion of adverse symptoms in different sex,age and the Han nationality,while the proportion of minority adverse reactions was very low,and there was no difference among the different sex and age(P>0.05).The main reasons for the reluctance of HIV/AIDS population to be vaccinated were(recommended by doctors)that HIV/AIDS patients could not be vaccinated(67.61%)and may have serious adverse reactions after the vaccination(19.72%).The factors affecting the vaccination were found by logistic regression analysis,whether they were worried about infecting novel coronavirus(OR = 0.121,95% CI = 0.083～0.640,P<0.001)and how much they knew about COVID-19 vaccine(OR = 28.932,95% CI = 15.469～54.115,P<0.001),safety of vaccination(OR = 13.953,95% CI = 4.819～40.404,P<0.001)and belief in the preventive effect of vaccine(OR = 14.017,95% CI = 4.752～41.348,P<0.001)were significant factors affecting vaccination.Among the 13 prefectures and cities,Dehong(20),Zhaotong(21)and Lincang(14)had the largest number of unvaccinated people.Conclusion After the mass vaccination,the rate of adverse reaction in HIV/AIDS population is low,the symptoms are mild,the correct and scientific advice and guidance from doctors and the full understanding of the harmfulness of the disease,the safety,prevention and effectiveness of the vaccine are the key to complete vaccination and put an end to vaccine hesitancy.

Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

Objective:To assess the consistency of ultrasound and dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis(GA), reasons of the differences were further analyzed.Methods:The ultrasound and DECT images of 150 knee joints from 147 patients diagnosed with gout at the Gout Specialty Clinic of Qingdao University Affiliated Hospital from February 2022 to October 2023 were retrospectively analyzed. According to anatomy, the knee joint was anatomically segmented into five regions: intra-articular, anterior, posterior, medial, and lateral.Location of monosodium urate (MSU) deposition was meticulously recorded. The Kappa consistency test was employed to assess the consistency of the two examination results in different regions of the knee joint. The McNemar chi-square test was utilized to conduct a differential analysis between DECT and ultrasound results.Results:Double contour sign(DCS) (81.2%, 92/112) was the most common intra-articular ultrasound sign in knee joints with GA. In the extra-articular region, MSU was commonly deposited in and around the popliteal tendon (ultrasound: 51.6%, 66/128; DECT: 54.7%, 70/128). Corresponding MSU deposits on DECT were found in 9 of 92 joints with DCS and in 9 of 49 joints with aggregates detected on ultrasound.In the assessment of MSU deposits, ultrasound showed an overall higher positive rate than DECT (87.3% vs. 72.3%, P=0.001), with poor consistency between the two examinations (Kappa=0.153). In distinct anatomical regions, ultrasound and DECT showed high consistency in the medial (Kappa=0.697) and lateral (Kappa=0.718) sides and the difference was not statistically significant ( P>0.05). Intra-articular (Kappa=0.289) and anterior (Kappa=0.303) regions exhibited only fair consistency, with statistically significant diagnostic differences ( P<0.05). When exclusively assessing cases with tophus, ultrasound and DECT demonstrated high consistency in the medial and lateral aspects(Kappa=0.685, 0.748) without statistical difference ( P>0.05). In the anterior region, the consistency between the two examinations was moderate (Kappa=0.256), while in the intra-articular region, the consistency of the two methods was lower (Kappa=0.147), and the differences was statistically significant ( P<0.001). Conclusions:Both ultrasound and DECT exhibit good diagnostic capabilities for gouty knee arthritis.However, the consistency between the two techniques varies in different anatomical locations. Clinical assessment should be tailored based on the specific anatomical position. DECT has an advantage in evaluating intra-articular MSU deposits, while ultrasound is more sensitive to detect early and scattered MSU deposits.

Objective:To assess the discriminatory value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System (F-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and to compare its performance with other risk stratification systems(RSS).Methods:A retrospective analysis was conducted on 325 patients (327 thyroid nodules) diagnosed postoperatively as FTC or FTA at Affiliated Hospital of Qingdao University from January 2016 to December 2023. The cases were divided into FTC group (81 nodules) and FTA group (246 nodules). The nodules were classified based on F-TIRADS, the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS), the 2015 American Thyroid Association guidelines (ATA guidelines), and the 2017 European Thyroid Association Thyroid Imaging Reporting and Data System (EU-TIRADS) by two ultrasound physicians. Multivariate Logistic regression analysis was used to identify independent predictors associated with FTC. Diagnostic performance of the 4 RSS was compared using postoperative pathological results as the gold standard.Results:Multivariate Logistic regression analysis showed maximum diameter, solid composition, hypoechogenicity, unclear or angular margins, marginal or ring calcifications, trabecular structure, and central blood flow were independent predictors of FTC( OR=1.914, 3.427, 9.926, 9.163, 45.918, 3.191, 8.936, respectively; all P<0.05). Within each RSS, the actual malignancy rate increased with higher risk categories, aligning closely with the recommended malignancy rates (except for ATA guidelines). The optimal cut-off values for distinguishing FTC from FTA were FTC risk 50%-90% in F-TIRADS, C-TIRADS 4B, moderately suspicious nodules in ATA guidelines, and EU-TIRADS 4, with areas under the curve of 0.916, 0.808, 0.827, and 0.836, respectively. F-TIRADS demonstrated the best overall performance (sensitivity: 82.72%, specificity: 82.93%), with significant differences compared with C-TIRADS, ATA guidelines, and EU-TIRADS (all P<0.05). Conclusions:F-TIRADS is highly effective in distinguishing FTA from FTC, outperforming C-TIRADS, ATA Guidelines, and EU-TIRADS. Clinicians should pay close attention to solid hypoechoic nodules with unclear or angular margins, marginal or ring calcifications, central blood flow, or a trabecular structure.

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.