Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

bjective　To analyze the drug resistance screening status and drug resistance influencing factors of high-risk groups of drug-resistant pulmonary tuberculosis in Qingdao, and to understand the inclusion of rifampicin patients in treatment, so as to provide a reference for the prevention and treatment of drug-resistant pulmonary tuberculosis. Methods　The medical records of 726 cases of drug-resistant pulmonary tuberculosis among high-risk populations registered in Qingdao from 2018 to 2022 were obtained from the National Health Insurance Information System of the China Center for Disease Control and Prevention. The drug resistance to five anti-tuberculosis drugs, namely isoniazid (INH), rifampicin (RFP), ethambutol (EMB), levofloxacin (Lfx), and amikacin (Am), in the high-risk populations of drug-resistant pulmonary tuberculosis was analyzed. Univariate and multivariate logistic regression were used toidentify factors influencing rifampicin resistance, and the detection and inclusion of treatment for rifampicin-resistant patients were evaluated. Results　Of the 726 subjects, 278 were drug-resistant, with a total drug resistance rate of 38.29%. The drug resistance for the five anti-tuberculosis drugs in descending order was: INH 25.90%(188/726), RFP 22.87%(166/726), Lfx 14.19%(103/726), EMB 11.29%(82/726), Am 2.48%(18/726). Analysis of the drug resistance spectrum showed that among those resistant to one drug, RFP was most common, accounting for 13.67% (38/278); among those resistant to two drugs, INH+RFP was predominant, accounting for 15.83% (44/278); among those resistant to three drugs, INH+RFP+Lfx was most frequent, at 7.19% (22/278); and among those resistant to four drugs, INH+RFP+EMB+Lfx was highest, at 6.12% (17/278). Multivariate logistic regression analysis of rifampicin resistance showed that compared with patients under 25 years of age, the risk of developing rifampicin resistance was lower in the groups aged 45 to under 65 and those aged 65 and above (OR=0.356, 95%CI: 0.181-0.700; OR=0.352, 95%CI: 0.170-0.729). Compared with migrant patients in other provinces, local patients from within the same county or district had a lower risk of developing rifampicin resistance (OR=0.599, 95%CI:0.383-0.962). Compared with patients who were smear-positive at the end of the second month of initial treatment, the risk of developing rifampicin resistance was higher in patients with relapse/return, failure of retreatment/chronic, and other categories of patients (OR=9.380, 95%CI:3.717-23.671;OR=25.749, 95%CI:8.037-82.490; OR=36.651, 95%CI:8.438-159.201). Conclusions　The situation of drug-resistant pulmonary tuberculosis in Qingdao cannot be ignored. Individuals under 25 years old, migrants from other provinces, and patients with relapse/return, failure of retreatment/chronic, and other categories are significant risk factors for developing rifampicin resistance in the high-risk groups of drug-resistant pulmonary tuberculosis.

Objective:To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation.Methods:Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2) and cisplatin (60 mg/m 2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results:The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI: 74.0% to 94.8%) and 50.3% (95% CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI: 88.9% to 100.0%) and 58.2% (95% CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI: 74.2% to 94.9%) and 53.5% (95% CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion:The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Objective:To investigate the iodine nutritional status of pregnant women in Qingdao and the effect of prevention and treatment of iodine deficiency disorders (IDD), so as to provide a basis for residents to supplement iodine scientifically, and take targeted prevention measures and adjust intervention strategies.Methods:In accordance with the requirements of the "National Iodine Deficiency Disorders Surveillance Program (2016 edition)" and "Shandong Iodine Deficiency Disorders Surveillance Program", the cluster sampling method was adopted to select pregnant women from 10 districts (cities) in Qingdao from 2018 to 2020, to investigate their basic information and thyroid disease history. Meanwhile, household edible salt samples and random urine samples were collected to detect iodine content.Results:A total of 3 000 pregnant women were monitored from 2018 to 2020, the median age was 31 years, and the median gestational age was 18 weeks. There were significant differences in the distribution of age, gestational age, whether senile puerpera, and pregnancy in different years ( H/χ 2 = 29.35, 81.03, 65.62, 77.34, P < 0.001). The median salt iodine of edible salt ( n = 3 000) and iodized salt ( n = 2 700) in pregnant women's homes were 23.02 and 23.70 mg/kg, respectively. The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt were 89.59% (2 419/2 700), 90.00% (2 700/3 000) and 80.63% (2 419/3 000). The comparison of qualified rate of iodized salt, coverage rate of iodized salt and consumption rate of qualified iodized salt among different years was statistically significant (χ 2 = 48.09, 36.62, 61.08, P < 0.001), the coverage rate of iodized salt and the consumption rate of qualified iodized salt showed a downward trend year by year (χ 2trent = 35.54, 29.50, P < 0.001). A total of 3 000 urine samples were collected from pregnant women and the median urinary iodine of pregnant women was 147.85 μg/L. The urinary iodine level in the third trimester was lower than that in the first and second trimesters ( P < 0.001). The urinary iodine level in the non elderly group was higher than that in the elderly group ( Z = - 6.66, P < 0.001). The urinary iodine level in the group without thyroid disease was higher than that in the group with thyroid disease ( Z = - 1.99, P = 0.047). The urinary iodine level in iodized salt group was higher than that in non-iodized salt group ( Z = - 2.42, P = 0.015). Conclusions:The iodine nutrition of pregnant women in Qingdao is generally at an insufficient level, and the risk of iodine deficiency is high, which needs attention. In recent years, the coverage rate of iodized salt and the consumption rate of qualified iodized salt in Qingdao have shown a downward trend, and have failed to meet the requirements of national standards. In the future, we should strengthen the monitoring and health education of IDD in pregnant women.

Objective:To investigate the iodine nutritional status of children in Qingdao City and the effects of prevention and treatment measures on iodine deficiency disorders (IDD), and to provide a scientific basis for guiding residents to scientifically supplement iodine, taking timely targeted prevention and control measures, and scientifically adjusting intervention strategies.Methods:According to "National Iodine Deficiency Disorders Surveillance Program (2016 edition)" and "Iodine Deficiency Disorders Surveillance Program of Shandong Province", from 2018 to 2020, using the cluster sampling method, children aged 8-10 years in Qingdao City were chosen to test their household salt iodine content and random urinary iodine content, and to examine their thyroid volume by B-ultrasonography, and the correlation between thyroid volume and physical development indexes was analyzed.Results:From 2018 to 2020, a total of 6 057 children were monitored, including 3 068 boys and 2 989 girls. The median of salt iodine and iodized salt iodine of children was 23.50 and 24.10 mg/kg. The qualified rate of iodized salt was 89.95% (4 832/5 372), the coverage rate of iodized salt was 88.69% (5 372/6 057), and the consumption rate of qualified iodized salt was 79.78% (4 832/6 057). There were significant differences in the qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt between different years (χ 2 = 135.26, 314.71, 342.87, P < 0.001). A total of 6 057 urine samples were collected from children, and the median of urinary iodine was 193.92 μg/L, of which 16.2% (979/6 057) were < 100 μg/L, and 22.5% (1 361/6 057) were ≥300 μg/L. There were statistically significant differences in the medians of urinary iodine between different years, gender and whether eating iodized salt ( H/Z = 37.25,-3.89,-5.69, P < 0.001), the median of urinary iodine in boys was higher than that of girls, and the median of urinary iodine in eating iodized salt group was higher than that of eating non-iodized salt group. There was no significant difference in the median of urinary iodine between different age ( H = 4.33, P = 0.119). The rate of goiter in children was 3.45% (71/2 057), and the difference between different years was statistically significant (χ 2 = 42.68, P < 0.001). The incidence of goiter in 2020 [7.31% (45/616)] was significantly higher than that in 2018 and 2019 [2.81% (18/641), 1.00% (8/800), P < 0.001]. Thyroid volume of children was positively correlated with height and weight ( r = 0.20, 0.22, P < 0.001). Conclusions:The iodine nutritional level of children aged 8-10 years in Qingdao City is appropriate. However, the incidence of goiter in children in some years is relatively high. The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt are all lower than the national standard for elimination of IDD, which should be paid attention to.

Objective:To evaluate the effect of prevention and control measures to drinking-water-borne endemic fluorosis in Qingdao, and to provide scientific basis for formulating prevention and control strategies.Methods:From 2019 to 2021, a full coverage surveillance was carried out in 1 146 villages in 7 drinking-water-borne endemic fluorosis areas in Qingdao, including the operation status of the water improvement and fluoride reduction project, the water fluoride content in the villages, and the prevalence of dental fluorosis among children aged 8-12 years.Results:From 2019 to 2021, all the 1 146 affected villages in Qingdao had improved their water supply, and the rates of water fluoride exceeding the standard were 7.16% (82/1 146), 1.40% (16/1 146) and 3.84% (44/1 146), respectively, and the differences between years were statistically significant (χ 2 = 48.36, P < 0.001). The detection rates of dental fluorosis in children aged 8-12 years were 3.11% (803/25 856), 2.68% (629/23 460) and 3.00% (655/21 846), respectively, and the differences between years were statistically significant (χ 2 = 8.26, P = 0.016). The detection rate of dental fluorosis among children in villages with qualified water fluoride (2.85%, 1 986/69 565) was lower than that in villages with excessive water fluoride (6.32%, 101/1 597), with a statistically significant difference (χ 2 = 67.74, P < 0.001). Conclusions:From 2019 to 2021, the effect of prevention and control measures to drinking-water-borne endemic fluorosis in Qingdao is significant and the detection rate of dental fluorosis in children is low, the detection rate of dental fluorosis in villages with qualified water fluoride is significantly lower than that in villages with excessive water fluoride. In the future, we should continue to strengthen water fluoride monitoring and engineering maintenance to ensure that the water fluoride content continues to be qualified and effectively reduce the harm of fluorosis.

Objective:To assess the operation and usage conditions of all water improvement projects in Qingdao, master the water fluoride content and the prevalence of dental fluorosis in children in drinking-water-borne endemic fluorosis villages, evaluate the prevention and control effect of water improvement project.Methods:From April to October in 2020, all drinking-water-borne endemic fluorosis villages in 7 cities (districts) of Qingdao were selected to investigate the operation and usage conditions of water improvement project, water fluoride and prevalence of dental fluorosis of 8 to 12 years old children. The prevention and control effect of water improvement project on drinking-water-borne endemic fluorosis in Qingdao was evaluated according to the control contents and criteria of drinking-water-borne endemic fluorosis.Results:There were 1 146 drinking-water-borne endemic fluorosis villages, the water improved rate of villages was 100.00% (1 146/1 146), the rate of normal operation of water improvement project was 99.91% (1 145/1 146). There were 1 130 villages with qualified water fluoride and the qualified rate was 98.60% (1 130/1 146). A total of 23 473 children aged 8 - 12 years old were examined, and 631 children were detected with dental fluorosis. The detection rate of dental fluorosis was 2.69% (631/23 473), the dental fluorosis index was 0.048, and the prevalence was negative. The detection rate of dental fluorosis of children in villages with excessive water fluoride (7.03%, 40/569) was higher than that in villages with qualified water fluoride (2.58%, 591/22 904, χ 2 = 41.235, P < 0.01). Conclusion:The operation and usage conditions of water improvement projects in 7 drinking- water-borne endemic fluorosis cities (districts) in Qingdao are good, and the detection rate of dental fluorosis in children is low, which has reached the national control standard.

Capsid ; Capsid Proteins ; Virus Assembly

Objective To observe the digestive system related symptoms in patients with early-middle stage Parkinson's disease (PD) and healthy subjects,and investigate the incidence of the symptoms and the influencing factors.Methods One hundred and eight PD patients with early and middle stage (Hoehn-Yahr staging 1-3) were admitted to Xuzhou Central Hospital and followed up for a long time.A questionnaire,including seven items of digestive system related symptoms selected from the PD Non-Motor Symptom Scale and the Scale for Outcomes in PD for Autonomic Symptoms (taste abnormalities,swallowing disorders,salivation,easy or early satiety,constipation,loose stools,fecal incontinence),and additional five items of digestive system related symptoms (loss of appetite,dry mouth,oral pain,nausea,vomiting),totally 12 items,was used in a survey on PD patients.Seventy-six healthy subjects in the physical examination center of the hospital served as control group,and conducted the same questionnaire survey.Results There was no statistically significant difference in age,gender,height,weight,body mass index (BMI) between the PD and control groups.In 108 PD patients,dry mouth accounted for 64 cases (59.26％),constipation 53 cases (49.07％) and taste abnormalities 40 cases (37.04％),followed by loss of appetite 35 cases (32.41％) and early satiety 26 cases (24.07％),swallowing disorders 20 cases (18.52％),nausea 11 cases (10.19％),salivation 10 cases (9.26％),oral pain seven cases (6.48％),vomiting four cases (3.70％),loose stools one case (0.87％).In 76 controls,taste abnormalities accounted for 13 cases (17.11％),early satiety six cases (7.89％),loss of appetite six cases (7.89％),nausea five cases (6.58％),salivation three cases (3.95％),oral pain one case (1.32％),and the rest zero.The incidence of constipation (x2=52.390,P＜0.01),dry mouth (x2=69.050,P＜0.01),early satiety (x2=8.128,P=0.004),loss of appetite (x2=16.010,P＜0.01),taste abnormalities (x2=8.642,P=0.003) and swallowing disorders (x2=15.790,P＜0.01) showed statistically significant difference between the two groups.Analysis of the influencing factors showed that male had an effect on constipation (95％CI 1.371-7.495,OR=3.205),early satiety (95％CI 4.227-282.913,OR=34.582),taste abnormalities (95％CI 6.620-88.942,OR=24.260) and swallowing disorders (95％CI 2.784-88.475,OR=22.906),while other factors such as age,body mass index,disease duration and motor symptom types had no effect on the occurrence of digestive system related symptoms.Conclusions Digestive system related symptoms in patients with PD include dry mouth,constipation,taste abnormalities,loss of appetite,early satiety,and swallowing disorders,which may be their unique symptoms.Male is a risk factor for taste abnormalities,swallowing disorders,early satiety and constipation.