[Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma: a prospective phaseâ ¡study].

Objective: To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC). Methods: This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. Results: A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%). Conclusion: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.

[The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma].

Objective: To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. Methods: This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. Results: By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. Conclusions: The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

A prospective study of drug-drug interaction between antiepileptic drugs and meropenem in patients in a tertiary hospital in China from January 2020 to March 2023.

OBJECTIVE: This study aimed to determine the minimum interaction between different antiepileptic drugs (AEDs) and meropenem (MEPM) for clinical treatment. PATIENTS AND METHODS: The data of 91 patients enrolled in the neurology department from January 2020 to March 2023 for clinical trials were measured and observed. Self-controlled studies were conducted to monitor the trough concentrations of valproic acid (VPA), carbamazepine (CBZ) and levotiracetam (LEV) before and after MEPM usage. Relevant indicators of liver and kidney function were also monitored. RESULTS: The serum VPA trough concentrations were 36.25±8.22 µg/ml at 24±12 h and 34.99±11.17 µg/ml at 96±12 h after MEPM use; the difference was significant (p<0.05). Decreased CBZ trough concentrations were also identified after MEPM usage (96±12 h), whereas LEV trough concentrations were not affected. An increased liver injury rate (χ2 =8.744, p<0.05) and a decreased kidney injury rate (χ2 =5.393, p<0.05) were found in the VPA group only. CONCLUSIONS: The interaction between VPA and MEPM decreased serum VPA concentrations, increased liver injury rates, and decreased kidney injury rates. In addition, the co-administration of MEPM and CBZ reduced serum CBZ concentrations. Clinicians should be aware of this potential interaction and closely monitor the relevant biochemical indices and number of seizures.

[Clinical characteristics and surgical outcomes of pediatric epiretinal membranes without specific etiologies].

Objective: To describe clinical characteristics and surgical outcomes of pediatric epiretinal membranes (ERMs) without specific etiologies. Methods: Medical data of a cohort of pediatric patients (≤14 years) who had ERMs without specific etiologies, underwent surgical removal from January 2019 to September 2021, and were followed up for at least 12 months were retrospectively reviewed. Age at presentation, chief complaints, color fundus photographs, optical coherence tomographic images, preoperative and postoperative visual acuities, anatomical changes, and postoperative complications were assessed. Results: There were 14 patients (17 eyes), including 5 females (6 eyes) and 9 males (11 eyes). The mean age at surgery was 6.31±2.91 years, and the follow-up duration was 17.3±9.5 months. Eight patients were found to have low vision in the school physical examination. Fifteen eyes had an appearance of cellophane macular reflex on fundus images. On optical coherence tomographic images, 10 eyes had"taco"folds, and 7 eyes had"ripple"folds. Five eyes had ellipsoid zone disruptions, while 12 eyes had ellipsoid zone integrity. The preoperative and postoperative best-corrected visual acuities in logMAR were 0.532±0.302 and 0.340±0.298. One patient suffered traumatic cataract and secondary retinal detachment postoperatively, and after further vitrectomy, the retina became attached. Conclusion: Pediatric ERMs without specific etiologies were mostly found in school-age children with cellophane macular reflex and"taco"folds. Vitrectomy may result in both potential visual acuity and macular anatomical improvements.

[Correlation of MYB/NFIB gene fusion with the grade and prognosis of head and neck adenoid cystic carcinoma and the concordance of two detection methods].

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

Clinicopathological features and prognostic factors of salivary gland myoepithelial carcinoma: institutional experience of 42 cases.

Myoepithelial carcinoma (MECA) is a rare type of carcinoma for which the clinicopathological features and prognostic factors have not yet been fully clarified. A retrospective study of 42 patients diagnosed with salivary gland MECA was performed, focusing on the clinicopathological features and prognostic factors. Of the 42 patients, 20 died of cancer, 20 lived without tumour, one lived with distant metastasis, and one was lost to follow-up. Overall, 69.0% had tumour recurrence, 16.7% had cervical nodal metastasis, and 21.4% had distant metastasis. The 5-year overall survival rate was 70.2%. Kaplan-Meier analysis revealed that patients with pathological positive lymph nodes (pN+), multiple recurrences of tumour, and higher histological grade had worse overall survival. Multivariate Cox analysis indicated pN+ and higher histological grade to be independent predictors of decreased survival. The 5-year overall survival rate in the pN0 group was 87.5%, while that in the pN+ group was 28.6%. In conclusion, myoepithelial carcinoma can be defined as a tumour with a high incidence of recurrence and poor prognosis, especially in pN+ patients. Pathological positive lymph nodes and histological grade may serve as predictors of survival.

Inhibition mechanism of cordycepin and ergosterol from Cordyceps militaris Link. against xanthine oxidase and cyclooxygenase-2.

Cordyceps militaris Link. (C. militaris) is an entomopathogenic fungus that parasitizes the pupa or cocoon of lepidopteran insect larvae, with various bioactive compounds. Cordycepin and ergosterol are the two active components in C. militaris. This study aimed to evaluate the inhibitory activity of cordycepin and ergosterol against xanthine oxidase (XO) and cyclooxygenase-2 (COX-2), as well as investigate the inhibition mechanism. Cordycepin could better inhibit XO (IC50 = 0.014 mg/mL) and COX-2 (IC50 = 0.055 mg/mL) than ergosterol. Additionally, surface hydrophobicity and circular dichroism (CD) spectra results confirmed the conformational changes in enzymes induced by cordycepin and ergosterol. Finally, cordycepin and ergosterol significantly decreased uric acid (UA) and inflammatory factors to normal level in mice with gouty nephropathy (GN). This study could provide theoretical evidence for utilization of C. militaris in hyperuricemia-management functional foods.

[A cross-sectional survey on the allocation of nursing human resources in burn centers in China].

Objective: To investigate the allocation of nursing human resources in burn centers in China. Methods: A cross-sectional survey was conducted. Using a self-designed questionnaire, a survey was carried out from January to March 2022 to investigate the January to December 2021 status of 39 burn centers in China that met the inclusion criteria based on six strategic regions and other regions, including the hospital grade and the region, the number of nurses and opening beds in the burn centers and burn intensive care units (BICUs), the age, working seniority in burn specialty, educational background, professional title, personnel employment, and turnover of nurses and training of newly recruited nurses in the burn centers. Results: This survey covered 30 provinces, municipalities, and autonomous regions in China (excluding Hong Kong Special Administrative Region, Macao Special Administrative Region, and Taiwan region of China). A total of 39 questionnaires were collected, all of which were valid. The 39 burn centers were located in 38 tertiary A hospitals and 1 tertiary B hospital, with 26 burn centers in strategic areas. The nurse/bed ratio of burn centers in the Greater Bay Area of Guangdong, Hong Kong, and Macao was the highest, while the nurse/bed ratio of burn centers in border ethnic minority area was the lowest. Except for the Chengdu-Chongqing Economic Circle, BICUs had been set up in burn centers in other regions. Among the 39 burn centers, the percentage of nurses aged 25 to 34 years was 51.21% (738/1 441), the percentage of nurses worked in burn specialty for less than 5 years was 31.16% (449/1 441), the percentage of nurses with bachelor's degree was 69.74% (1 005/1 441), and the percentage of nurses with nursing professional title was 44.14% (636/1 441), which were the highest. There were significant differences in the employment of nurses, the percentage of permanent nurses in burn centers in the collaborative development zone of Beijing-Tianjin-Hebei was 82.48% (113/137), while the percentage of permanent nurses in burn centers in important military strategic area was only 9.42% (34/361); the turnover rate of nurses was 9.03% (143/1 584), among which the turnover rate of nurses was 18.14% (80/441) in burn centers in important military strategic area. The training for newly recruited nurses in 39 burn centers was mainly based on the guidance of senior nurses and the pre-job education+specialist training. Conclusions: The burn nursing human resources in strategic areas in China are seriously insufficient and unevenly distributed, with unstable nurse team and lack of standardized specialist training. In particular, the nursing human resources in BICUs need to be equipped and supplemented urgently.

[Change trends and related risk factors of disease burden on mesothelioma in Jiangsu Province from 1990 to 2019].

Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.

[Willingness of HIV non-occupational post-exposure prophylaxis and related factors among men who have sex with men in Beijing].

Objective: To examine the willingness of HIV non-occupational post-exposure prophylaxis (nPEP) among MSM and factors related were also assessed. Methods: The respondent-driven sampling method was used to recruit MSM for a face-to-face interview with a structured questionnaire,the sample size was estimated at 600 subjects. Demographic data, sexual behavior, awareness, and willingness regarding nPEP were collected. The factors related to willingness to nPEP were assessed using complex logistic regression. Results: A total of 14 rounds were recruited and 608 MSM subjects were included in the study. The average age was (41.6±11.0) years. 55.4% (95%CI: 49.4%-59.4%) were aware of nPEP, and 4.5% (95%CI: 2.9%-6.2%) have used its. 35.9% (95%CI: 31.1%-40.7%) expressed interest in taking nPEP if needed. Among the reasons for not being willing to take nPEP, 68.9% (244/354) were never heard of nPEP, and 24.6% (87/354) were a fluke mentality. The multivariate logistic analysis results showed that the willingness of nPEP awareness of MSM was related to the group aged 25-39 years old (aOR=1.80, 95%CI: 1.01-3.20), knowing a group of HIV prevention knowledge (aOR=2.43, 95%CI: 1.52-3.90), group of consistent condom use in anal sex in the past half of year (aOR=1.76, 95%CI: 1.11-2.79). Conclusions: The use rate of nPEP among MSM in Beijing was low, and the willingness to use in the future also needs to be improved. The training of social organizations should be strengthened to improve the role of peer education in promoting nPEP.

[Acetaldehyde dehydrogenase 2 ameliorates lung endothelial barrier and balances mitochondrial dynamics in mice with acute lung injury].

OBJECTIVE: To investigate the protective effects of acetaldehyde dehydrogenase 2 (ALDH2) against lipopolysaccharide (LPS)- induced acute lung injury (ALI) in mice and explore the possible mechanisms. METHODS: Sixty C57BL/6J mice were equally randomized into Sham group, LPS group, LPS + Alda-1 (an ALDH2 agonist) group, and LPS + Daidzin (an ALDH2 inhibitor) group. After the treatment, the wet/dry lung mass ratio of the mice was measured, and the lung permeability was evaluated with Evans Blue (EB). The lung tissue pathologies were evaluated with HE staining and transmission electron microscopy. Serum levels of 4-hydroxynonenal (4-HNE) were measured with ELISA, and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined to measure oxidative stress levels. The expressions of ALDH2, ZO-1, Occludin, Mfn2, OPA1, Drp1, Fis1, and nuclear Nrf2 and HO-1 proteins in the lung tissues were detected using Western blotting. RESULTS: The mice with LPS-induced ALI showed severe disruption of the lung tissue structure and endothelial cell tight junctions with significantly increased the lung permeability (P<0.01), increased levels of 4-HNE and MDA (P<0.01), decreased activities of CAT and SOD (P<0.01), lowered expressions of ALDH2, ZO-1, Occludin, Mfn2, and OPA1 proteins, and increased expressions of Drp1, Fis1, and nuclear Nrf2 and HO-1 proteins (P<0.05, P<0.01). Treatment with Alda-1 significantly improved lung tissue pathologies and mitochondrial damage in ALI mice (P<0.01), increased the expressions of ALDH2, ZO-1, Occludin, OPA1, Mfn2, and nuclear Nrf2 and HO-1 proteins, and lowered the expressions of Drp1 and Fis1 proteins (P<0.05, P<0.01). Compared with Alda-1, treatment with Daidzin significantly increased the lung permeability, exacerbated mitochondrial damage, decreased the expression of ALDH2, ZO-1, Occludin, Mfn2, OPA1, and nuclear Nrf2 and HO-1 proteins, and increased expressions of Drp1 and Fis1 proteins (P<0.05, P<0.01). CONCLUSION: ALDH2 can ameliorate LPSinduced lung endothelial barrier damage in ALI mice by maintaining the balance of mitochondrial dynamics and inhibiting oxidative stress, and the mechanism may be related to the Nrf2/HO-1 pathway.

[HIV infection rate, high-risk behavior and pre-exposure prophylaxis/post-exposure prophylaxis in men who have sex with men in Beijing].

Objective: To understand the incidence of HIV infection, high risk behaviors and pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) utilization in men who have sex with men (MSM) in Beijing. Methods: Sample size was estimated to be 1 227 persons and 207 person year respectively in the survey and the cohort by using Epi Info 7.0 software. Using convenient sampling method, MSM were recruited by using Wechat app. Questionnaire was completed online to collect the information about demographic characteristics, high risk behavior, and utilization of PrEP/PEP of the MSM. MSM collected dry blood spot (DBS) samples by themselves, and mailed the DBS samples to laboratory for HIV nucleic acid testing. Open cohort was established and those with HIV negative nucleic acid testing results were followed up. Non-conditional binary logistic regression method was used to identify the associated factors for high risk anal sex in the last month and having multiple homosexual partners in the last month. Results: A total of 1 147 MSM were recruited, and follow up for 236 person years was conducted in 956 MSM with negative HIV nucleic acid testing results. The detection rate of new HIV infection was 1.3 per 100 person-years (3/236). During the last month, the proportions of consistent condom use in anal sex and oral sex were 50.7% (238/469) and 4.9% (23/469). In the MSM, 5.9% (43/723) had sex with HIV positive partners in the last month. 9.8% (103/1 049) used PrEP, and 8.7% (91/1 049) used PEP. The proportion of consistent condom use in PrEP and PEP were 34.3% (24/70) and 72.2% (39/54) respectively. Logistic regression analysis revealed that compared with those who used no PrEP/PEP, those who used PrEP/PEP were more likely to have unprotected anal sex in the last month (aOR=3.16, 95%CI:1.45-7.18), and more likely to have multiple homosexual partners in the last month (aOR=2.64, 95%CI:1.19-6.30), and compared with those who used no Rush Popper or drugs in the last month, those who used Rush Popper or drugs in the last month were more likely to have unprotected anal sex in the last month (aOR=2.34, 95%CI:1.67-3.30), and more likely to have multiple homosexual partners (aOR=2.42,95%CI:1.76-3.33). Conclusions: It is necessary to strengthen the health education to promote condom use and introduce the harm of drug use in MSM. In PrEP and PEP services, it is still necessary to suggest consistent condom use for MSM.

[Clinical factors affecting the prognosis of lower gingival squamous cell carcinoma].

OBJECTIVE: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them. METHODS: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen). RESULTS: of different invasion depth groups were compared using Mann-Whitney U test.P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio (HR) and 95% confidence interval (CI) of prognostic factors of LGSCC. RESULTS: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible (P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients (P < 0.05). CONCLUSION: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.

[Epidemiological study of incidence of systematic lupus erythematosus in Yinzhou, Ningbo, 2016-2021].

Objective: To characterize the incidence density of systematic lupus erythematosus (SLE) in Yinzhou District of Ningbo from 2016 to 2021, and compare the age and gender specific differences. Methods: A retrospective cohort study was conducted based on the related data from 2015 to 2021 collected from the Health Information Platform of Yinzhou. Suspected SLE cases in local residents were identified by fuzzy matching of International Classification of Diseases 10th edition code "M32" or Chinese text "lupus". The classification criteria from Systemic Lupus International Collaboration Clinics-2012 and The European League Against Rheumatism/American College of Rheumatology-2019 were used for case verification. SLE cases were identified with specific algorithm based on verification results, and new cases were identified with 1 year as the washout period. The incidence density and 95%CI were estimated by Poisson distribution. Results: From 2016 to 2021, a total of 1 551 921 permanent residents were registered in Yinzhou, in whom 51.52% were women. The M(Q1,Q3) age at enrollment was 40.38 (27.54, 53.54) years. The M(Q1,Q3) of follow-up person-years was 3.83 (0.41, 5.83) years. There were 451 new SLE cases, in which 352 were women (78.05%). The 6-year incidence density was 8.14/100 000 person-years (95%CI: 7.41/100 000 person-years-8.93/100 000 person-years) for the total population, 3.68/100 000 person-years (95%CI: 2.99/100 000 person-years-4.48/100 000 person-years) for men and 12.37/100 000 person-years (95%CI: 11.11/100 000 person-years- 13.73/100 000 person-years) for women. The incidence density in men appeared a small peak at 20-29 years old, and began to increase with age from 40 years old. The incidence density in women was highest in age group 20-29 years (16.57/100 000 person-years) and remained to be high until 30-79 years old. The incidence density of SLE in Yinzhou show no significant temporal trend from 2016 to 2021 (men: P=0.848; women: P=1.000). Conclusions: The incidence density of SLE in Yinzhou from 2016 to 2021 was similar to those of other areas in China. SLE has a high incidence in women, especially in the young and elderly, suggesting that more attention should be paid to the diagnosis and treatment of SLE in women.

Evaluation of chronic drug-induced electrophysiological and cytotoxic effects using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Introduction: Cardiotoxicity is one of the leading causes of compound attrition during drug development. Most in vitro screening platforms aim at detecting acute cardio-electrophysiological changes and drug-induced chronic functional alterations are often not studied in the early stage of drug development. Therefore, we developed an assay using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that evaluates both drug-induced acute and delayed electrophysiological and cytotoxic effects of reference compounds with clinically known cardiac outcomes. Methods: hiPSC-CMs were seeded in 48-well multielectrode array (MEA) plates and were treated with four doses of reference compounds (covering and exceeding clinical free plasma peak concentrations -fCmax values) and MEA recordings were conducted for 4 days. Functional-electrophysiological (field-potentials) and viability (impedance) parameters were recorded with a MEA machine. Results: To assess this platform, we tested tyrosine-kinase inhibitors with high-cardiac risk profile (sunitinib, vandetanib and nilotinib) and low-cardiac risk (erlotinib), as well as known classic cardiac toxic drugs (doxorubicin and BMS-986094), ion-channel trafficking inhibitors (pentamidine, probucol and arsenic trioxide) and compounds without known clinical cardiotoxicity (amoxicillin, cetirizine, captopril and aspirin). By evaluating the effects of these compounds on MEA parameters, the assay was mostly able to recapitulate different drug-induced cardiotoxicities, represented by a prolongation of the field potential, changes in beating rate and presence of arrhythmic events in acute (<2 h) or delayed phase ≥24 h, and/or reduction of impedance during the delayed phase (≥24 h). Furthermore, a few reference compounds were tested in hiPSC-CMs using fluorescence- and luminescence-based plate reader assays, confirming the presence or absence of cytotoxic effects, linked to changes of the impedance parameters measured in the MEA assay. Of note, some cardiotoxic effects could not be identified at acute time points (<2 h) but were clearly detected after 24 h, reinforcing the importance of chronic drug evaluation. Discussion: In conclusion, the evaluation of chronic drug-induced cardiotoxicity using a hiPSC-CMs in vitro assay can contribute to the early de-risking of compounds and help optimize the drug development process.

[Clinical analysis of 66 cases of pseudo fever].

Some patients who present with a "fever" may only have a localized increase in body surface temperature, while their core body temperature remains normal. This phenomenon is commonly referred to as pseudo fever. A retrospective analysis of clinical data from January 2013 to January 2020 at our fever clinic showed that 66 adolescents were diagnosed with pseudo fever. These patients typically showed a gradual increase in axillary temperature after their cold symptoms had disappeared. Most patients reported no significant complaints other than mild dizziness. Laboratory tests showed no significant abnormalities, and antipyretics were ineffective in lowering their body temperature. Pseudo fever is a relatively independent clinical phenomenon that is distinct from functional fever or simulated fever, and its underlying mechanism remains to be studied.

[Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype].

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.