Status in clinical and molecular characteristics of differentiated thyroid carcinoma in children and adolescents / 中华外科杂志

The epidemiological, clinical, and molecular characteristics of differentiated thyroid carcinoma (DTC) in children and adolescents are different from those in adults. The incidence of DTC in children and adolescents is very low, with high rates of lymph node metastasis, extra-thyroidal extension and recurrence, but mortality is lower than that in adults. Younger children with DTC tend to show a higher rate of recurrence, more lymph node metastases, and more extra-thyroidal extension. Furthermore, studies on molecular characteristics suggest that the diversity of gene mutations causes the clinical manifestations of DTC in children and adolescents that are different from those in adults. The incidence of gene fusion is significantly higher than in adults, while the incidence of point mutations is lower than in adults, which may be closely related to clinicopathological characteristics such as high tumor aggressiveness and poor prognosis.

Protective effect of recombinant Schistosoma japonicum cystatin against acute kidney injury associated with acute liver failure in mice / 中国血吸虫病防治杂志

OBJECTIVE@#To evaluate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute kidney injury induced by acute liver failure and unravel the underlying mechanism, so as to provide insights into the clinical therapy of acute kidney injury.@*METHODS@#Twenty-four male C57BL/6J mice at ages of 6 to 8 weeks were randomly divided into the normal control group, rSj-Cys control group, lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) model group and LPS/D-GaIN + rSj-Cys treatment group, of 6 mice each group. Mice in the LPS/D-GaIN group and LPS/D-GaIN + rSj-Cys group were intraperitoneally injected with LPS (10 μg/kg) and D-GaIN (700 mg/kg), and mice in the LPS/D-GaIN + rSj-Cys group were additionally administered with rSj-Cys (1.25 mg/kg) by intraperitoneal injection 30 min post-modeling, while mice in the rSj-Cys group were intraperitoneally injected with rSj-Cys (1.25 mg/kg), and mice in the normal control group were injected with the normal volume of PBS. All mice were sacrificed 6 h post-modeling, and mouse serum and kidney samples were collected. Serum creatinine (Cr) and urea nitrogen (BUN) levels were measured, and the pathological changes of mouse kidney specimens were examined using hematoxylin-eosin (HE) staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were detected using enzyme-linked immunosorbent assay (ELISA), and the expression of inflammatory factors and pyroptosis-related proteins was quantified in mouse kidney specimens using immunohistochemistry. In addition, the expression of pyroptosis-related proteins and nuclear factor-kappa B (NF-κB) signaling pathway-associated proteins was determined in mouse kidney specimens using Western blotting assay.@*RESULTS@#HE staining showed no remarkable abnormality in the mouse kidney structure in the normal control group and the rSj-Cys control group, and renal tubular injury was found in LPS/D-GaIN group, while the renal tubular injury was alleviated in LPS/D-GaIN+rSj-Cys treatment group. There were significant differences in serum levels of Cr (F = 46.33, P < 0.001), BUN (F = 128.60, P < 0.001), TNF-α (F = 102.00, P < 0.001) and IL-6 (F = 202.10, P < 0.001) among the four groups, and lower serum Cr [(85.35 ± 32.05) μmol/L], BUN [(11.90 ± 2.76) mmol/L], TNF-α [(158.27 ± 15.83) pg/mL] and IL-6 levels [(56.72 ± 4.37) pg/mL] were detected in the in LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (all P values < 0.01). Immunohistochemical staining detected significant differences in TNF-α (F = 24.16, P < 0.001) and IL-10 (F = 15.07, P < 0.01) expression among the four groups, and lower TNF-α [(106.50 ± 16.57)%] and higher IL-10 expression [(91.83 ± 5.23)%] was detected in the LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (both P values < 0.01). Western blotting and immunohistochemistry detected significant differences in the protein expression of pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3 (NLRP3) (F = 24.57 and 30.72, both P values < 0.001), IL-1β (F = 19.24 and 22.59, both P values < 0.001) and IL-18 (F = 16.60 and 19.30, both P values < 0.001) in kidney samples among the four groups, and lower NLRP3, IL-1β and IL-18 expression was quantified in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (P values < 0.05). In addition, there were significant differences in the protein expression of NF-κB signaling pathway-associated proteins p-NF-κB p-P65/NF-κB p65 (F = 71.88, P < 0.001), Toll-like receptor (TLR)-4 (F = 45.49, P < 0.001) and p-IκB/IκB (F = 60.87, P < 0.001) in mouse kidney samples among the four groups, and lower expression of three NF-κB signaling pathway-associated proteins was determined in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (all P values < 0.01).@*CONCLUSIONS@#rSj-Cys may present a protective effect against acute kidney injury caused by acute liver failure through inhibiting inflammation and pyroptosis and downregulating the NF-κB signaling pathway.

Impact of COVID-19 pandemic on the management of imported malaria in China / 中国血吸虫病防治杂志

OBJECTIVE@#To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance.@*METHODS@#All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021).@*RESULTS@#A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ2 = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ2 = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ2 = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ2 = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ2= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ2 = 3.95, P < 0.05).@*CONCLUSIONS@#The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.

Molecular detection and phylogenetic analysis of Wolbachia infection in common mosquito species in Henan Province / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the infection and genotypes of Wolbachia in common mosquito species in Henan Province, so as to provide insights into management of mosquito-borne diseases.@*METHODS@#Aedes, Culex and Anopheles samples were collected from cowsheds, sheepfolds and human houses in Puyang, Nanyang City and Xuchang cities of Henan Province from July to September, 2022, and the infection of Wolbachia was detected. The 16S rDNA and wsp genes of Wolbachia were amplified and sequenced. Sequence alignment was performed using the BLAST software, and the obtained 16S rDNA gene sequence was compared with the sequence of the 16S rDNA gene in GenBank database. In addition, the phylogenetic trees were created based on 16S rDNA and wsp gene sequences using the software MEGA 11.0.@*RESULTS@#A total 506 female adult mosquitoes were collected from three sampling sites in Nanyang, Xuchang City and Puyang cities from July to September, 2022. The overall detection of Wolbachia was 45.1% (228/506) in mosquitoes, with a higher detection rate in A. albopictus than in Cx. pipiens pallens [97.9% (143/146) vs. 50.6% (85/168); χ2 = 88.064, P < 0.01]. The detection of Wolbachia in Cx. pipiens pallens was higher in Xuchang City (96.8%, 62/64) than in Nanyang (15.6%, 7/45) and Puyang cities (27.1%, 16/59) (χ2 = 89.950, P < 0.01). The homologies of obtained Wolbachia 16S rDNA and wsp gene sequences were 95.3% to 100.0% and 81.7% to 99.8%. Phylogenetic analysis based on wsp gene sequences showed Wolbachia supergroups A and B in mosquito samples, with wAlbA and wMors strains in supergroup A and wPip and wAlbB strains in supergroup B. Wolbachia strain wAlbB infection was detected in A. albopictus in Puyang and Nanyang Cities, while Wolbachia strain wPip infection was identified in A. albopictus in Xuchang City. Wolbachia strain wAlbA infection was detected in Cx. pipiens pallens sampled from three cities, and one Cx. pipiens pallens was found to be infected with Wolbachia strain wMors in Nanyang City.@*CONCLUSIONS@#Wolbachia infection is commonly prevalent in Ae. albopictus and Cx. pipiens pallens from Henan Province, and Wolbachia strains wAlbB and wAlbA are predominant in Ae. albopictus, while wPip strain is predominant in Cx. pipiens pallens. This is the first report to present Wolbachia wMors strain infection in Cx. pipiens pallens in Henan Province.

Clinicopathological analysis of nuclear protein in testis midline carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype and prognosis of nuclear protein in testis (NUT) midline carcinoma. Methods: Twenty-four resection cases of NUT midline carcinoma diagnosed at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China from January 2018 to September 2022, were collected, and retrospectively analyzed for their clinicopathological characteristics. Relevant literature was reviewed. Results: All 24 cases of NUT midline carcinoma occurred in the chest or head and neck, including 14 men and 10 women, with a median age of 40 years. Histological examination showed that the tumors were poorly differentiated, with solid nested or sheet-like arrangement, small to medium-sized cells, sparse cytoplasm and coarse granular chromatin, including 5 cases with abrupt squamous epithelial differentiation. Immunohistochemistry showed that all 24 cases were positive for NUT protein, while 16 cases were p63 positive, 19 cases were p40 positive, 15 out of 18 cases were CK5/6 positive. Follow-up data were obtained for 21 patients (follow-up time range, 1-21 months), of which 11 survived, 10 died, and 3 were lost to follow-up. Conclusions: NUT midline carcinoma is a rare and highly aggressive malignancy with unique histological, immunophenotypic and molecular features. It has a poor prognosis.

Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder / 中华病理学杂志

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

Deep-learning based bioactive therapeutic peptides generation and screening

Many bioactive peptides demonstrated therapeutic effects over-complicated diseases, such as antiviral, antibacterial, anticancer, etc. Similar to the generating de novo chemical compounds, with the accumulated bioactive peptides as a training set, it is possible to generate abundant potential bioactive peptides with deep learning. Such techniques would be significant for drug development since peptides are much easier and cheaper to synthesize than compounds. However, there are very few deep learning-based peptide generating models. Here, we have created an LSTM model (named LSTM_Pep) to generate de novo peptides and finetune learning to generate de novo peptides with certain potential therapeutic effects. Remarkably, the Antimicrobial Peptide Database has fully utilized in this work to generate various kinds of potential active de novo peptide. We proposed a pipeline for screening those generated peptides for a given target, and use Main protease of SARS-COV-2 as concept-of-proof example. Moreover, we have developed a deep learning-based protein-peptide prediction model (named DeepPep) for fast screening the generated peptides for the given targets. Together with the generating model, we have demonstrated iteratively finetune training, generating and screening peptides for higher predicted binding affinity peptides can be achieved. Our work sheds light on to the development of deep learning-based methods and pipelines to effectively generating and getting bioactive peptides with a specific therapeutic effect, and showcases how artificial intelligence can help discover de novo bioactive peptides that can bind to a particular target.

Comparación de los programas de residencia en urología de Estados Unidos y China / Comparison of urology residency training between the United States and China

Objetivo: Este estudio compara el estado actual y las características de los programas de formación de la residencia de urología de EE. UU. y China.Métodos: Se realizó una evaluación comparativa de la trayectoria, la estructura, el plan de estudios, la experiencia quirúrgica, las actividades académicas, los sistemas de evaluación y otros aspectos de la formación de los residentes en China y EE. UU.Resultados: Los programas de residencia de urología de China y EE. UU. difieren entre sí en muchos aspectos. Los requisitos de acceso al programa de residencia de urología de EE. UU. son más rigurosos, y la especialización de la formación en EE. UU. está más condensada. Además, en EE. UU. la formación clínica e investigativa es más práctica y el sistema de evaluación es más diverso y basado en competencias. Adicionalmente, las oportunidades laborales tras la residencia difieren sustancialmente entre estos dos países. Convertirse en cirujano urológico independiente no es el objetivo específico de la formación de la residencia urológica en China, y esto requiere mucho más tiempo de formación que en EE. UU.Conclusión: Los programas de residencia de urología en EE. UU. y China tienen un formato y unas características propias. La formación en China se centra en técnicas y procedimientos generales, mientras que los programas en EE. UU. siguen un plan de estudios más estandarizado. Tanto EE. UU. como China pueden ser un buen complemento para la creación de programas de formación que, en última instancia, proporcionen una atención de alta calidad a los pacientes (AU)

Objective: This study compares the present status and traits of urology residency programs in the United States and China.Methods: The flow path, structure, curriculum, operative experience, scholarly activities, evaluation systems and other aspects of training were comparatively evaluated between China and the United States.Results: Urology residency training programs are different between China and the United States in many aspects. Admission requirements for the United States urology residency program are more rigorous, and the specialty training program in the United States is more concentrated. Furthermore, residency programs in USA have much more practical clinical and research training, and their evaluation process is more diverse, and it has been designed to assess competencies. Moreover, job opportunities after residency substantially differ between these two countries. Becoming an independent urologic surgeon is not the specific goal of the Urology residency training program in China, and it would require more training time than in the United States.Conclusion: Urology residency training programs in the United States and China have a unique format and characteristics. The training programs in China are focused on general techniques and procedures, while training programs in USA follow a more standardized curriculum. Both USA and China may complement each other to create training programs that would ultimately provide high-quality patient care (AU)

El papel de los parámetros metabólicos de la 18F-FDG PET/TC en el linfoma linfoblástico pediátrico / The role of 18F-FDG PET/CT metabolic parameters in pediatric lymphoblastic lymphoma

Objetivo: Este estudio retrospectivo tuvo como objetivo evaluar el papel de los parámetros metabólicos de la 18F-FDG PET/TC en el linfoma linfoblástico pediátrico (LBL).Métodos: Treinta pacientes con LBL se sometieron a 42 exploraciones. Los parámetros metabólicos, que incluyeron el valor máximo de captación estandarizado (SUVmax), el volumen tumoral metabólico total (TMTV) y la glucólisis de lesión total (TLG), se midieron en la PET/TC basal. Se realizaron análisis univariantes y multivariantes de la supervivencia para evaluar su valor pronóstico. Doce pacientes se sometieron a PET/TC después del régimen de reinducción, y se calcularon la sensibilidad, la especificidad, el valor predictivo positivo (VPP), el valor predictivo negativo (VPN) y la precisión de la PET/TC para predecir la recaída.Resultados: Los pacientes con estadio IV tuvieron una TMTV más alta que los que tenían un estadio III (p=0,031). Además, los pacientes con T-LBL o afectación mediastínica tenían una TMTV y TLG altos (p<0,05). No hubo diferencias significativas en los parámetros metabólicos de la PET/TC entre los pacientes con diferente evolución (p>0,05). Los niños con una TMTV baja (<242,91cm3) tuvieron una mejor EFS a los 3 años comparados con aquellos con una TMTV elevada (88.9% vs. 56,3%; p=0,036). El SUVmax y el TLG no fueron predictivos de la EFS (p=0,874; p=0,152). Sin embargo, ninguno de los parámetros metabólicos de la PET/TC basales fueron factores pronósticos independientes para los resultados del LBL pediátrico. La PET/TC realizada después del régimen de reinducción presentó una mayor sensibilidad (50% vs. 0%) y VPN (90% vs. 83,3%) para predecir la recaída que la TC sola.Conclusiones: Los parámetros metabólicos de la PET/TC de referencia no fueron predictivos de los resultados en los niños con LBL. La PET/TC realizada después del régimen de reinducción tuvo una mejor sensibilidad y VPN que la TC sola, y una exploración

Objective: This retrospective study aimed to evaluate the role of metabolic parameters of 18F-FDG PET/CT in pediatric lymphoblastic lymphoma (LBL).Methods: Thirty patients with LBL underwent 42 scans. Metabolic parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) were measured at baseline PET/CT. Univariate and multivariate analysis for survival were performed to assess their prognostic value. Twelve patients underwent PET/CT after reinduction regime, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for predicting relapse were calculated.Results: Patients with stage IV had a higher TMTV than those with stage III (P=0.031). Besides, patients with T-LBL or mediastinal involvement had a high TMTV and TLG (P<0.05). There was no significant difference in PET/CT metabolic parameters between patients with different outcomes (P>0.05). Children with a low TMTV (<242.91cm3) had a better 3-year EFS compared with those with a high TMTV (88.9% vs. 56.3%; P=0.036). SUVmax and TLG were not predictive of EFS (P=0.874; P=0.152). However, none of the metabolic parameters of baseline PET/CT were independent prognostic factors for outcomes of pediatric LBL. PET/CT underwent after reinduction regime present with higher sensitivity (50% vs. 0%) and NPV (90% vs. 83.3%) for predicting relapse than CT alone.Conclusions: Metabolic parameters of baseline PET/CT were not predictive of outcomes in children with LBL. PET/CT done after the reinduction regime had better sensitivity and NPV than CT alone, and a negative scan could be a reliable indicator for sustained remission (AU)

Fatality assessment and variant risk monitoring for COVID-19 using three new hospital occupancy related metrics

BackgroundThough case fatality rate (CFR) is widely used to reflect COVID-19 fatality risk, its use is limited by large temporal and spatial variation. Hospital mortality rate (HMR) is also used to assess the severity of COVID-19, but HMR data is not directly available except 35 states of USA. Alternative metrics are needed for COVID-19 severity and fatality assessment. MethodsNew metrics and their applications in fatality measurements and risk monitoring are proposed here. We also introduce a new mathematical model to estimate average hospital length of stay for death (Ldead) and discharges (Ldis). Multiple data sources were used for our analysis. FindingsWe propose three new metrics, hospital occupancy mortality rate (HOMR), ratio of total deaths to hospital occupancy (TDHOR) and ratio of hospital occupancy to cases (HOCR), for dynamic assessment of COVID-19 fatality risk. Estimated Ldead and Ldis for 501,079 COVID-19 hospitalizations in US 34 states between Aug 7, 2020 and Mar 1, 2021 were 14.0 and 18.2 days, respectively. We found that TDHOR values of 27 countries are less spatially and temporally variable and more capable of detecting changes in COVID-19 fatality risk. The dramatic changes in COVID-19 CFR observed in 27 countries during early stages of the pandemic were mostly caused by undiagnosed cases. Compared to the first week of November, 2021, the week mean HOCRs (mimics hospitalization-to-case ratio) for Omicron variant decreased 34.08% and 65.16% in the United Kingdom and USA respectively as of Jan 16, 2022. InterpretationThese new and reliable measurements for COVID-19 that could be expanded as a general index to other fatal infectious diseases for disease fatality risk and variant-associated risk monitoring. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, medRxiv, and bioRxiv for peer-reviewed articles, preprints, and research reports on risk and health care evaluation for COVID-19 using the search terms "hospital occupancy mortality rate", "ratio of total deaths to hospital occupancy", "ratio of hospital occupancy to case" up to Jan 20, 2022. No similar concepts or studies were found. No similar mathematical models based on "hospital occupancy mortality rate" for the estimation of hospital length of stay for deaths and discharges have been identified to date. Added value of the studyOur new metrics, HOMR and TDHOR, mimic HMR for COVID-19 fatality risk assessment but utilize readily available data for many US states and countries around the world. HOCR mimics hospitalization-to-case ratio for COVID-19. We also provide evidence that explains why COVID-19 CFR has such dramatic changes at the beginning of a COVID-19 outbreak. We have additionally provided new metrics for COVID-19 fatality risk dynamic monitoring including Omicron variant and showed that these metrics provided additional information. Implications of all the available evidenceThe results of this study, including average hospital length of stay for deaths and discharges for over 500,000 COVID-19 hospitalizations in the US, can aid county, state, and national leaders in making informed public health decisions related to the ongoing COVID-19 pandemic. This is the first study to provide quantitative evidence to address why CFR has a such a large variation at the beginning of the COVID-19 pandemic in most countries and will hopefully encourage more countries to release hospital occupancy data, which we show is both useful and easy information to collect. The new metrics introduced by our study are effective indicators for monitoring COVID-19 fatality risk, as well as potentially fatal COVID-19 variants, and could also be expanded to other fatal infectious diseases.

Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

The immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.

Recommended Strategies for Physician Burnout, a Well-Recognized Escalating Global Crisis Among Neurologists

Several indexes are used to classify physician burnout, with the Maslach Burnout Inventory currently being the most widely accepted. This index measures physician burnout based on emotional exhaustion, detachment from work, and lack of personal achievement. The overall percentage of physicians with burnout is estimated to be around 40%, but the proportion varies between specialties. Neurology currently has the second-highest rate of burnout and is projected to eventually take the top position. The purpose of this review is to provide a comprehensive overview focusing on the causes and ramifications of burnout and possible strategies for addressing the crisis. Several factors contribute to burnout among neurologist, including psychological trauma associated with patient care and a lack of respect compared to other specialties. Various interventions have been proposed for reducing burnout, and this article explores the feasibility of some of them. Burnout not only impacts the physician but also has adverse effects on the overall quality of patient care and places a strain on the health-care system. Burnout has only recently been recognized and accepted as a health crisis globally, and hence most of the proposed action plans have not been validated. More studies are needed to evaluate the long-term effects of such interventions.

Autonomic Disturbances in Acute Cerebrovascular Disease / 神经科学通报·英文版

Autonomic disturbances often occur in patients with acute cerebrovascular disease due to damage of the central autonomic network. We summarize the structures of the central autonomic network and the clinical tests used to evaluate the functions of the autonomic nervous system. We review the clinical and experimental findings as well as management strategies of post-stroke autonomic disturbances including electrocardiographic changes, cardiac arrhythmias, myocardial damage, thermoregulatory dysfunction, gastrointestinal dysfunction, urinary incontinence, sexual disorders, and hyperglycemia. The occurrence of autonomic disturbances has been associated with poor outcomes in stroke patients. Autonomic nervous system modulation appears to be an emerging therapeutic strategy for stroke management in addition to treatments for sensorimotor dysfunction.

Analysis on long-term trends of cervical cancer mortality and years of life lost in Tianjin, 1999-2015 / 中华流行病学杂志

Objective: To analyze the mortality and years of life lost (YLL) trends of cervical cancer in Tianjin, and provide references for the research and prevention programs of cervical cancer. Methods: Mortality rate, standard mortality rate, cumulative rate (0-74 years-old) and truncated rate (35-64 years-old) of cervical cancer from 1999 to 2015 were calculated. The annual percentage change of the mortality rate and YLL rate were analyzed by using Joinpoint regression analysis, and the trend in different age-groups were analyzed. Results: From 1999 to 2015, 1 741 cases died of cervical cancer in Tianjin, the average crude mortality rate was 2.15/100 000. The average age-standardized rate of (ASR) China and ASR world were 1.47/100 000 and 1.50/100 000 respectively. The average YLL was 3 347.97 person-years. Deaths occurred in those aged 0-34 years, 35-64 years and 65 years and over accounted for 3.10%, 57.84% and 39.06% of the total, respectively. The mortality rate of cervical cancer in urban area was higher than that in rural area, with a ratio of 1.37∶1 between urban area and rural area. The age-specific mortality rate of cervical cancer during 1999-2015 increased with age. Two peaks of mortality rate were observed in those aged 50 years and aged 75 years, during 2014-2015. From 1999 to 2011, the mortality rate of cervical cancer was stable (APC=-0.2%, P=0.80), but there was a rapid increase from 2011 to 2015 (APC=21.6%, P<0.01). But group aged 20-49 years, it showed an upward trend from 1999 to 2015 (APC=6.9%, P<0.01). For group aged 50-69 years, it showed a downward trend from 1999 to 2007 (APC=-9.2%, P<0.01), and an upward trend from 2007 to 2015 (APC=14.5%, P<0.01). For group aged 70 years and over, it showed a downward trend from 1999 to 2009 (APC=-10.2%, P<0.01), but the difference in the mortality were not significant from 2009 to 2015 (APC=7.8%, P=0.10). Since 2008, the YLL rate of cervical cancer in group aged 50-70 years had exceeded that in group aged >70 years and the gap gradually widened. Conclusions: There had been a rapid increase trend of cervical cancer mortality since 2011 in Tianjin. Women aged 50-70 years were the main group of life loss.

Application of computer-assisted system in surgery for pediatric solid pseudopapillary tumor / 中华实用儿科临床杂志

Objective@#To explore the value of Hisense computer-assisted surgical systems (CAS) for precise surgery of pediatric solid pseudopapillary tumor.@*Methods@#A total of 5 cases with pancreatic solid pseudopapi-llary tumor who were admitted at the Affiliated Hospital of Qingdao University from June 2015 to September 2018 were adopting.Upper abdominal 64-slice dynamic enhanced computed tomography (CT) scan was performed.3D models were created by computer-assisted surgery systems.Based on 3D model, surgical planning, preoperative simulated tumor resection, intraoperative assisted guidance were performed.Operation time, intraoperative blood loss volume, blood transfusion rate were analyzed.@*Results@#Hisense CAS three-dimensional reconstruction could clearly show the adjacent relationship between pancreas, tumor and peripheral vascular organs.According to the preoperative virtual resection, pancreatic tumor resection was more accurate.Postoperative pathological results were solid pseudopapillary tumor of the pancreas.Among them, 2 tumors were located in the head of the pancreas, 1 case was located in the pancreatic neck, and 2 cases in the tail of the pancreas.The operation time was 150-360 min, with an average of 279 min.The average intraoperative blood loss was 40 mL, of which the minimum amount of bleeding was 5 mL, and the blood transfusion rate was 40%(2/5 cases). Surgical tumor removal was achieved successfully in 5 cases.All children were followed up for 6 months to 3 years, and no recurrence or metastasis was observed.@*Conclusions@#Three-dimensional reconstruction of computer-assisted surgery system can clearly show the adjacent relationship between tumor and surroun-ding vascular organs, and help to make the best surgical plan before surgery to improve the accuracy and safety of the operation.

Abuse of diphenoxylate and related factors of forced drug abstainer in Gansu province / 中华流行病学杂志

Objective: To investigate the prevalence of diphenoxylate abuse and related factors of forced drug abstainer in Gansu province. Methods: By using a self-designed questionnaire, an epidemiologic investigation was carried out among 2 108 forced drug abstainer selected from the compulsory isolation detoxification center of Gansu province. A case-control study was conducted to analyze the factors related with diphenoxylate abuse. Results: The diphenoxylate abuse rate among forced drug abstainer in Gansu was 19.8% (406/2 046), ranking first in medical drug abuse. Multiple logistic regression analysis showed that factors as relieving withdrawal symptoms (OR=2.08, 95%CI: 1.01- 4.32), ways to obtain diphenoxylate (other ways: OR=1.00; regular clinic: OR=27.67, 95%CI: 2.64-289.82; friend: OR=0.01, 95%CI: 0.01-0.03), degree of euphoria (high: OR=1.00; medium: OR =3.36, 95%CI: 1.18-9.55; low: OR=26.16, 95%CI: 10.30-66.42), years of drug abuse (<5 years: OR=1.00; 10-15 years: OR=2.48, 95%CI: 1.02-6.04), abuse at home or in friend's house (OR=3.04, 95%CI: 1.08-8.68), abuse in car (OR=0.05, 95%CI: 0.00-0.68) and detoxification for the first time (OR=0.61, 95%CI: 0.43-0.86) were the possible influencing factors for diphenoxylate abuse. Conclusions: The prevalence of diphenoxylate abuse in forced drug abstainer in Gansu was relatively high. Reasons of abusing, the way to obtain diphenoxylate, whether using drug together with friends, degree of euphoria, years of abuse, abuse place and times for detoxification were related factors influencing the abuse of diphenoxylate.

Association between AOX1, IRF4 methylation in peripheral blood leukocyte DNA and the risks of breast cancer: a case-control study / 中华流行病学杂志

Objective: To understand the relationship between AOX1, IRF4 gene methylation status in peripheral blood leukocyte DNA, as well as its interaction with environmental factors, and the risk of breast cancer. Methods: A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014. Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4. The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression, and Excel software was used to analyze the additive interaction effect. Results: Individuals without AOX1 methylation had a 1.37-fold (95%CI: 1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation. AOX1 methylation interacted with fungi intake (OR=2.06, 95%CI: 1.12-3.79) and physical activity (OR=2.18, 95%CI: 1.16-4.09) synergistically, on the risk for breast cancer, but no additive interaction effects were observed. Non-methylation of IRF4 could increase the risk for breast cancer, with statistical significance (OR=1.71, 95%CI: 0.99-7.43). Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors. Conclusion: Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.

Epidemiological and pathogenic characteristics of mumps in Fujian province, 2005-2017 / 中华流行病学杂志

Objective: To understand the epidemiological and etiological characteristics of mumps in Fujian province, 2005-2017. Methods: All the reported mumps cases were collected through the National Notifiable Disease Information Management System, 2005-2017. Active search and interviews were conducted to collect the information on vaccination of mumps. Throat swab specimens were collected for cells culture, genotyping and gene sequence analysis on mumps virus (MuV). Results: A total of 83 959 cases of mumps were reported in Fujian province from 2005 to 2017, with an average annual incidence of 17.6 per 100 000. Since 2007, the incidence appeared increasing but then decreasing, reaching the lowest level (7.5 per 100 000), after the setup of a monitoring program. Annually, the onset time of mumps showed an obvious two seasonal peaks, one from April to July, with a weakening trend, and the other from October to January with a rising trend. Most of the mumps cases occurred among students, kindergarten and scattered children (89.2%, 5 814/6 517), children aged 5-9 years (38.8%, 2 527/6 517), with cases reported from every region. Program from the pathogen surveillance showed that the transmission chain of G genotype mumps virus did exist in Fujian. Data from the sequence analysis revealed that mutations in the nucleotide of G genotype strain in 2015 had led to mutation of 6 amino acid sites in the SH gene coding region, resulting in the differences appearing in both nucleotide and amino acid homology with type A vaccine strain. Conclusions: The incidence of mumps decreased annually, in Fujian. Prevention programs should focus on primary and secondary school students. In Fujian province, we also noticed the transmission chain of mumps G genotype with some amino acid mutations in the SH gene coding region. Monitor programs on both epidemiologic and etiology, should be strengthened.

Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.