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Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

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Objective To clarify whether the use of dynamic coronary artery roadmap(DCR)technology in a low-dose mode with 7.5 frames per second during coronary intervention can further reduce the total radiation dose,fluoroscopy time,and contrast agent usage.Methods A total of 94 patients,who received coronary angiography at the Shanghai Tongji Hospital of China between July 2022 and December 2022,were enrolled in this study.The patients were randomly divided into DCR group(n=53)and control group(n=41).DCR technology was used in the DCR group to guide the performance of percutaneous coronary intervention(PCI),while low-dose mode coronary angiography was adopted in the control group.The total air kerma(AK),dose-area product(DAP),intraoperative fluoroscopy time,and contrast agent usage were compared between the two groups.Results In the DCR group AK was(597.9±222.8)mGy,which was significantly lower than(717.0±326.8)mGy in the control group(P=0.039);DAP was(33.2±13.3)Gycm2/s,which was also remarkably lower than(41.3±21.5)Gycm2/s in the control group(P=0.027).In the DCR group and the control group,the intraoperative fluoroscopy time was(9.8± 3.3)min and(12.1±4.3)min respectively(P＜0.01),and the contrast agent usage was(122.3±19.0)mL and(130.5± 28.5)mL respectively(P=0.116).Conclusion In a low-dose mode during coronary intervention,the use of DCR technology can further reduce radiation dose,fluoroscopy time,and contrast agent usage.(J Intervent Radiol,2024,33:236-239)

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Objective To explore the drug resistance mechanism and characteristics of carbopenem-resistant pseudo-monas aeruginosa(CRPA)in our hospital.Methods BD phoenix 100 automatic bacterial identification and drug sensitivity an-alyzer was used to identify and detect the drug sensitivity of the strains.The minimum inhibitory concentration(MIC)of ceftazi-dime/acibactam was detected by micro broth dilution method.The modified carbapenem inactivation method(mCIM)and colloi-dal gold immunochromatography were used to detect the carbapenemase phenotype of the strains.The whole genome sequencing was used to detect the carbapenemase resistance gene and ST typing of the screened positive strains.Results A total of 22 strains of clinically isolated CRPA were collected,of which the antibacterial drugs with the lowest resistance rate were ceftidine/avibatan(22.7% ),followed by gentamicin and amikacin(27.3% ),pyracillin/tazobactam(59.09% ),cefuroxime(63.6% ).Ceftazide and aminotransferrane(77.27% ),ciprofloxacin(86.36% ),levofloxacin(95.45% ).There are a total of 5 strains(22.7% )of carbapenems in 22 CRPA by phenotypic detection.The whole genome sequencing results show that 4 strains of ST549 CRPA carry metal β-lactamase IMP-45 and serine β-lactamase OXA-1,OXA-50,one strain is ST245 CRPA carries metal β-lactamase NDM-1,that is,all five CRPA strains produce metal β-lactamase.Conclusion The resistance rate of CRPA to ceftazidime/avibactam is low in our hospital.Carbapenemase-producing is not the main mechanism of CRPA resistance to car-bapenems,while metal β-Lactamase-producing is the main mechanism of CRPA resistance to ceftazidime avibactam.

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Objective:To assess the clinical significance of next-generation sequencing (NGS)-based IGH/ IGK gene rearrangement analysis versus flow cytometry (FCM) in diagnosing minimal residual disease (MRD) of children with acute B-cell lymphoblastic leukemia (B-ALL). Methods:Clinical data, NGS-MRD and FCM-MRD findings at the initial diagnosis and after induction chemotherapy of 85 children diagnosed as B-ALL in Children′s Hospital of Nanjing Medical University from July 2019 to July 2021, were retrospectively analyzed.The sensitivity of the two methods, and the positive rate were compared by χ2 test or Fisher′ s test.The correlation was identified by Spearman correlation analysis. Results:Dominant clone sequences were detected in all children at the initial diagnosis by NGS, while selection markers were identified by FCM in 75(88.2%) patients.Positive MRD rate detected by NGS-MRD was significantly higher than that of FCM-MRD at the same time point after induction chemotherapy[31.8%(27/85) vs.9.4%(8/85), P<0.001]. Compared with those of FCM-MRD, NGS-MRD had good sensitivity (100.0%), specificity (75.3%) and negative predictive value (100.0%), and the positive predictive value was 29.6%.MRD results detected by NGS were consistent with that of FCM ( r=0.569, P<0.001). By July 27, 2022, 2 patients with NGS-MRD (+ )FCM-MRD (-)relapsed during maintenance chemotherapy. Conclusions:NGS is highly consistent with FCM in the detection of MRD in children with B-ALL, which is more sensitive.The combination of NGS-MRD and FCM-MRD benefits more in monitoring MRD in children with B-ALL after induction chemotherapy.

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Virtual reality (VR) medical education resources are widely used in theoretical teaching and clinical skill training, but they are still in the primary stage. VR medical education resources have higher requirements for the compatibility of resource management platforms, greater difficulties and costs in resource construction, and stronger demand for copyright protection, but there is still a lack of effective VR medical resource management platforms and operating mechanisms to mobilize the enthusiasm of all participants in resource construction and application. For the key problems in VR medical education resource management, this article proposes a cloud VR medical education resource management framework based on blockchain and cloud VR technology, specifically designs the function of each module, elaborates on its operation and management mechanisms, and analyzes the effect of such framework, so as to improve the efficiency of cloud VR medical education resource management and promote the construction and shared application of cloud VR medical education resources.

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In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

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Objective:To investigate the clinicopathological features of metastatic ovarian tumors from digestive system.Methods:The clinicopathological and follow-up data of 21 patients with metastatic ovarian tumor from digestive system were collected from April 2006 to January 2020 in the Maternity Hospital of Dalian Women and Children′s Medical Group. The pathological slides were reviewed, immunostained by EnVision method, and the clinicopathological features were summarized.Results:Twenty-one cases, aging from 26 to 66 years (average 41.5 years), were treated with chief complaint of abdominal pain, menstrual disorder or pelvic mass. The incidence of bilateral ovarian tumor was 81.0% (17/21), with a diameter of 0.2 to 20.0 cm. Most of tumors were solid and cystic, nodular or lobulated. Microscopically, tumor cells diffusely infiltrated ovarian stroma, accompanied with stromal proliferation and luteinization obviously. Metastatic gastric cancers were mainly signet-ring cell carcinomas, with cytokeratin 7 (CK7) positive, tail homeobox transcription factor 2 (CDX2) and cytokeratin 20 (CK20) partially positive, paired-box gene 8 (PAX8) and special AT-rich sequence binding protein 2 (SATB2) negative; metastatic colorectal cancers were mainly characterized by atypical glands, forming single cells or cribriform structure; metastatic appendix tumors were mostly low-grade tumor cells similar to ovarian borderline tumors and abundant extracellular mucinous, accompanied by peritoneal pseudomyxoma. The CK7 and PAX8 were negative, while the CK20, CDX2 and SATB2 were positive in patients with metastatic ovarian tumor from colorectal cancer and appendix tumor. The average follow-up time was 36 months, 18 patients relapsed within 5 years, 15 patients died; 3 patients were lost to follow-up.Conclusions:The ovarian metastatic tumors from digestive system are mostly bilateral, mainly solid and cystic. Microscopically, they show diffuse interstitial infiltration of tumor cells. The diagnosis should be combined with medical history, clinical symptoms, gross and histological features of tumor and immunohistochemistry, which should be mainly differentiated from primary mucinous ovarian tumor. The overall prognosis is poor.

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Objective:To evaluate the clinical value of human papillomavirus (HPV) E6/E7 mRNA testing in cervical cancer screening under 30 years old.Methods:The clinical data of 330 young women (less than 30 years old) with minor abnormalities of thinprep cytologic test (TCT) screening for in Dalian Women′s and Children′s Medical Center (Group) Chunliu Region from January 2020 to June 2021 were retrospectively analyzed. Among them, 165 patients underwent HPV DNA typing test (DNA group), and 165 patients underwent HPV E6/E7 mRNA typing test (mRNA group). The positive rate of cervical intraepithelial neoplasia (CIN) Ⅱ and above (CIN Ⅱ +) was compared between two groups, and the positive rates of CIN Ⅱ + in different high risk HPV types. Results:The positive rate of high risk HPV types in mRNA group was significantly lower than that in DNA group: 32.7% (54/165) vs. 47.9% (79/165), and there was statistical difference ( χ2 = 7.87, P<0.05). There was no statistical difference in the incidence of CIN Ⅱ + of patients with positive of high risk HPV types between DNA group and mRNA: 45.6% (36/79) and 59.3% (32/54), P>0.05. There was no statistical difference in the incidence of CIN Ⅱ + of patients with HPV 16, 18 or 45 positive between DNA group and mRNA group: 38.5% (10/26) and 6/10, P>0.05. The incidence of CIN Ⅱ + of patients without HPV 16, 18 or 45 positive in mRNA group was significantly higher than that in DNA group: 60.9% (28/46) vs. 41.3% (26/63), and there was statistical difference ( P<0.05). Conclusions:Without increasing the rate of missed diagnosis, HPV E6/E7 mRNA testing plays an important shunt role in women under 30 years old, and the predicted value of CIN Ⅱ + is higher for patients who are not infected with HPV16/18/45 with HPV E6/E7 mRNA testing.

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Objective:To determine the effects of menopausal stage, age and other associated risk factors on symptoms of anxiety and depression among women in a community in Beijing.Methods:This study was a community-based prospective cohort. Participants who had transitioned through natural menopause, completed two or more depressive and anxiety symptoms evaluations, aged 35 to 64 years, and did not use hormone therapy were selected from the Peking Union Medical College Hospital aging longitudinal cohort of women in midlife to this analysis. The primary outcome variables were depressive and anxiety symptoms, assessed by hospital anxiety and depression scale (HADS). The generalized estimation equation was used in the statistical analysis.Results:Followed up from 2006 to 2014, 430 women and 2 533 HADS assessments were retained in the cohort. Depressive symptoms were more common than anxiety symptoms during all menopausal stages. The incidences of depressive and anxiety symptoms were 14.5% (19/191) and 3.1% (4/191) in the premenopausal -3 stage, respectively. The incidence increased in both menopausal transition and postmenopausal stage, with the highest incidence in the +1c stage [20.6% (155/751) and 8.8% (66/751), respectively]. However, these differences were not statistically significant (all P>0.05). Depressive symptoms were highest in the ≥60-<65 age group [20.8% (74/355)], and anxiety symptoms were highest in the ≥50-<55 age group [8.2% (62/754)]; but there were no statistical significances between different age groups and depressive and anxiety symptoms (all P>0.05). Multivariable analysis showed that high body mass index, low education status, and poor health status were independently associated with depressive symptoms (all P<0.05), and that poor health status, trouble falling asleep, and early awakening were independently associated with anxiety symptoms (all P<0.01). Conclusions:Depressive and anxiety symptoms are more common during menopausal transition and postmenopausal stage compared with reproductive stage. Depressive symptoms are more common than anxiety symptoms. To screen and assess depressive and anxiety symptoms in perimenopausal women is essential, especially for women with high risk factors.

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Objective:To investigate the clinical efficacy and safety of fruquintinib in elderly patients with advanced metastatic colorectal cancer who failed chemotherapy.Methods:Ninety-nine elderly patients with advanced metastatic colorectal cancer who failed chemotherapy in No. 904 Hospital of Joint Logistics Support Force from September 2018 to July 2020 were selected. All patients were given furquintinib capsules, 1 time/d, 5 mg/time, and 28 days was 1 cycle. All patients were treated continuously for 2 cycles and the effect was observed. The patient's recent anti-tumor efficacy was counted. The serum levels of carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) in patients before and after treatment were compared. The safety of the medication during the patient's treatment was recorded, and the Kaplan-Meier method was used for survival analysis.Results:A total of 99 elderly patients with advanced metastatic colorectal cancer who failed chemotherapy were treated for 2 cycles, with an objective response rate (ORR) of 22.22% (22/99) and a clinical control rate (CCR) of 75.76% (75/99). The serum levels of CA125, CA199 and CEA after treatment were lower than those before treatment (all P<0.05). The drug adverse reactions in 99 patients during the treatment were mostly grade Ⅰ-Ⅱ, and grade Ⅲ-Ⅳ were rare. The most common gradeⅠ-Ⅱ adverse reactions were hypertension (45.45%, 45/99), hand-foot syndrome (40.40%, 40/99), and elevated aspartate transferase (36.36%, 36/99). Followed up for 12 months, 5 cases were lost to follow-up, the follow-up rate was 94.95%, the median progression-free survival time of the remaining 94 patients was 5.62 months (95% CI 3.57-8.75 months), and the median overall survival time was 8.41 months (95% CI 4.85-11.14 months). Conclusions:Fruquintinib has good efficacy in the treatment of elderly patients with advanced metastatic colorectal cancer who failed chemotherapy. It can reduce the levels of tumor markers, the survival status of patients is good, and the adverse reactions are controllable.

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BACKGROUND: Nattokinase is a fibrinolytic enzyme that has huge market value as a nutritional supplement for health promotion. In order to increase nattokinase yields, fermentation conditions, strains, cultivation media, and feeding strategies have been optimized. Nattokinase has been expressed using several heterologous expression systems. Pichia pastoris heterologous expression system was the alternative. RESULTS: This report aimed to express high levels of nattokinase from B. subtilis natto (NK-Bs) using a Pichia pastoris heterologous expression system and assess its fibrinolytic activity in vivo. Multicopy expression strains bearing 1-7 copies of the aprN gene were constructed. The expression level of the target protein reached a maximum at five copies of the target gene. However, multicopy expression strains were not stable in shake-flask or high-density fermentation, causing significant differences in the yield of the target protein among batches. Therefore, P. pastoris bearing a single copy of aprN was used in shake-flask and high-density fermentation. Target protein yield was 320 mg/L in shake-flask fermentation and approximately 9.5 g/L in high-density fermentation. The recombinant nattokinase showed high thermo- and pH-stability. The present study also demonstrated that recombinant NK-Bs had obvious thrombolytic activity. CONCLUSIONS: This study suggests that the P. pastoris expression system is an ideal platform for the large-scale, low-cost preparation of nattokinase.

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Methyl parathion hydrolase (MPH) hydrolyses methyl parathion efficiently and specifically. Herein, we produced MPH from Plesiomonas sp. M6 using a Pichia pastoris multi-copy expression system. The original signal peptide sequence of the target gene was removed, and a modified coding sequence was synthesised. Multi-copy expression plasmids containing MPH were constructed using pHBM905BDM, and used to generate recombinant strains containing 1, 2, 3 or 4 copies of the MPH gene. The results showed that a higher target gene copy number increased the production of recombinant MPH (MPH-R), as anticipated. The expression level of the recombinant strain containing four copies of the MPH gene was increased to 1.9 U/ml using 500 ml shake flasks, and the specific activity was 15.8 U/mg. High-density fermentation further increased the target protein yield to 18.4 U/ml. Several metal ions were tested as additives, and Ni2+, Co2+ and Mg2+ at a concentration of 1 mM enhanced MPH-R activity by 196%, 201% and 154%, respectively. Enzyme immobilisation was then applied to overcome the difficulties in recovery, recycling and long-term stability associated with the free enzyme. Immobilised MPH-R exhibited significantly enhanced thermal and long-term stability, as well as broad pH adaptability. In the presence of inhibitors and chelating agents such as sodium dodecyl sulphate (SDS), immobilised MPH-R displayed 2-fold higher activity than free MPH-R, demonstrating its potential for industrial application.

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Depression is one of most common psychiatric disorders, and the detailed molecular mechanism remains to be fully elucidated. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophic factor that is decreased and closely involved in the development of depression. Noncoding RNAs are central regulators of cellular activities that modulate target genes. However, the roles of long noncoding RNA (lncRNA) MIR155HG and miRNA-155 (miR-155) in the pathophysiology of depression are unclear. In the present study, we aimed to explore the effects of lncRNA MIR155HG and miR-155 on the development of depression and uncover the underlying molecular mechanism. Real-time quantitative polymerase chain reaction was used to examine the expression of MIR155HG and miR-155. Western blotting was applied to measure the expression of BDNF. A luciferase reporter assay was utilized to determine the regulatory relationship between MIR155HG and miR-155. Our current work found that lncRNA MIR155HG and BDNF levels decreased while miR-155 levels increased in the hippocampal region of CUMS (chronic unpredictable mild stress) mice, a well-accepted mouse model of depression. Moreover, MIR155HG rescued while miR-155 exacerbated the depression-like behaviors of CUMS mice. Through bioinformatics analysis and luciferase reporter assays, we found that MIR155HG directly bound to and negatively modulated the expression of miR-155. Moreover, increased miR-155 was found to repress the expression of BDNF, a critical neurotrophic factor that has been reported to alleviate the depression-like behaviors of CUMS mice. Our present study revealed that lncRNA MIR155HG protected CUMS mice by regulating the miR-155/BDNF axis. Our study aimed to understand the pathophysiology of depression and provided potential therapeutic targets to diagnose and treat depression.

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Objective:To explore the clinical characteristics, possible causes and treatment methods of anaphylactoid reactions related to PICC catheterization.Methods:A retrospective analysis of the data of 27 patients with anaphylactoid reactions in 3 933 PICC catheters from October 2018 to February 2020.Results:The incidence of anaphylactoid reactions was 0.69%(27/3 933), its clinical symptoms were mainly skin reactions, some of which were complicated with respiratory, digestive, cardiovascular system and other symptoms. There was no difference in the incidence of different genders, diagnosis, and history of allergy ( χ2 value was 2.233, 0.839, 0.027, P>0.05). The incidence of patients younger than 60 years old was higher than that of patients older than 60 ( χ2 value was 12.821, P<0.01); the incidence of two catheters with different coatings was higher than that of uncoated catheters ( χ2 value was 27.195, 84.203, P<0.01). Twenty six patients continued the catheterization after the symptoms relieved, and one patient stopped the catheterization. Conclusion:The incidence of anaphylactoid reactions related to PICC, which is more common in catheters or the stylet wire is coated. It is recommended to use a large amount of saline to flush the catheter to reduce or avoid coating materials into the blood, so as to effectively control the occurrence and severity of such complications.

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Objective:To analyze the clinical phenotypes and prenatal diagnosis of a pedigree with oculo-facio-cardio-dental (OFCD) syndrome.Methods:A pregnant woman at 17 gestational weeks was admitted to the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School in 2017 for genetic counseling. Genetic tests as performed for the proband (the pregnant woman), her husband, and the induced fetus of last pregnancy genetic test and the detected variants were analyzed and verified by chromosomal microarray analysis (CMA), multiplex ligation-dependent probe amplification (MLPA) and quantitative real time-polymerase chain reaction (Q-PCR). The detection platform established by MLPA and Q-PCR technology was used to perform prenatal diagnosis of the present pregnancy. Other family members were screened for BCOR gene mutation. Related mutation types were retrieved from ClinVar database with term of " BCOR", and related literature from CNKI and PubMed with terms of "OFCD syndrome", " BCOR gene", and "oculo facio cardiac dental syndrome" to summarize the clinical manifestations, mutation type and pathogenesis of this disease. Results:The proband has congenital cataracts, long face, congenital atrial septal defect, and severe dental malformations, which were consistent with the clinical features of OFCD syndrome. WES suggested that the proband and her induced fetus were suspected of having a large submicroscopic deletion of the exons of BCOR gene, which was confirmed by CMA, MLPA and Q-PCR, with a 105 kb deletion containing BCOR exons 1-15. The amniotic fluid genetic analysis of the present pregnancy showed that the fetus has a normal female karyotype, and did not carry the same BCOR gene copy number abnormality as the proband. The child grew and normally developed without any characteristic manifestations of OFCD syndrome during follow-up. Other families of the proband did not show clinical features of OFCD syndrone, and no BCOR gene copy number abnormality was detected. A total of 35 cases of BCOR gene mutation types related to OFCD syndrome were retrieved from ClinVar database. The data analysis revealed that the differences in clinical manifestations between Lenz microphthalmos syndrome and OFCD syndrome were mainly caused by different mutation types of BCOR gene. Among the 90 retrieved cases of OFCD syndrome obtained through literature, only one case was reported in China. Analysis of these 90 cases showed that the characteristic manifestations of OFCD syndrome, involving the eye, face, heart, teeth, and skeletal system. OFCD syndrome were confirmed in the proband and her induced fetus according to the clinical manifestation and the mutation type of BCOR gene. Conclusions:The clinical manifestations of OFCD syndrome are complicated, caused by various mutation types of BCOR. Systematic molecular genetic technology can be effectively applied for gene and prenatal diagnosis of OFCD syndrome.

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Higher alcohols are one of the main by-products of Saccharomyces cerevisiae in brewing. High concentration of higher alcohols in alcoholic beverages easily causes headache, thirst and other symptoms after drinking. It is also the main reason for chronic drunkenness and difficulty in sobering up after intoxication. The main objective of this review is to present an overview of the flavor characteristics and metabolic pathways of higher alcohols as well as the application of mutagenesis breeding techniques in the regulation of higher alcohol metabolism in S. cerevisiae. In particular, we review the application of metabolic engineering technology in genetic modification of amino transferase, α-keto acid metabolism, acetate metabolism and carbon-nitrogen metabolism. Moreover, key challenges and future perspectives of realizing optimization of higher alcohols metabolism are discussed. This review is intended to provide a comprehensive understanding of metabolic regulation system of higher alcohols in S. cerevisiae and to provide insights into the rational development of the excellent industrial S. cerevisiae strains producing higher alcohols.

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Early non-pharmaceutical interventions (NPIs) are crucial to prevent and control of COVID-19 pandemic. We established a stochastic non-classical SEIR NPIs model (ScEIQRsh) which can quantify the three kinds of NPIs measures simultaneously to mimic the clustered intra-family or intra-acquaintance spreading pattern of COVID-19 under the effective integrated NPIs in Mainland China. Model simulation demonstrated that measures to diminish contactable susceptible (Sc), such as home confinement, travel constraint, social distancing etc. and measures to avoid delay of diagnosis and hospitalized isolation ({eta}) were more effective but consumptive than contact tracing ({kappa}, {rho}). From fitted model by MCMC method, the proportion of asymptomatic infectors was 14.88% (IQR 8.17%, 25.37%). The association between air temperature and the fitted transmission rate ({beta}) of COVID-19 suggests that COVID-19 pandemic would be seasonal with the optimal temperature range of 5{degrees}C-14{degrees}C and peak of 10{degrees}C for spreading, and vaccine is indispensable to ultimate prevention COVID-19.

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Over 10 percent of recovered and discharged patients retested positive for SARS-CoV-2, raising a public health concern whether they could be potential origins of infection. In this study, we found that detectable viral genome in discharged patients might only mean the presence of viral fragments, and could hardly form an infection origin for its extremely low concentration.

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BackgroundAntiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. MethodsOur study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. FindingsThis study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoints, the average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14, were similar between groups (all P>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical(P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. ConclusionsLPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. FundingThis study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004 and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).

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Objective To investigate the clinicopathological characteristics of primary ovarian mucinous adenocarcinoma.Methods The clinical data of 28 patients with primary ovarian mucinous adenocarcinoma from April 2006 to December 2018 in Dalian Maternity Hospital Affiliated to Dalian Medical University were retrospectively analyzed.The pathological sections were reviewed,and the clinicopathological characteristics were analyzed by immunohistochemical staining.Results Among 28 patients,the average age of patients was 46.5 (22 to 64) years.Ten cases were found by health examination,15 cases showed lower abdominal discomfort,and 3 cases had irregular vaginal bleeding.Pelvic ultrasound examination showed heterogeneous internal echoes in adnexal region,and serum tumor marker levels did not significantly increase.The diameters of tumors were 8 to 32 cm,with an average of 16.5 cm.The unilateral ovarian tumor was in 26 cases,and bilateral ovarian tumor was in 2 cases.Most of tumors were solid-cystic with viscous liquid or jelly-like substance inside the cystic,accompanied with solid papillae or nodules.Microscopically,tumors were composed with gastrointestinal epithelium.Eighteen cases had borderline mucinous tumors with focal fusion infiltrating carcinoma;10 cases had fusion infiltrating carcinoma dominant,while there were 2 cases whose tumor exhibited focal invasive infiltration.Immunohistochemical result showed that the positive rates of cytokeratin (CK) 7,CK20 and tail-type homeobox gene (CDX) 2 were 100.0％ (28/28),71.4％ (20/28) and 53.6％ (15/28);the positive rates of paired box gene (PAX) 8 and special AT-rich sequence-binding protein (SATB) 2 were 14.3％ (4/28) and 10.7％ (3/28).According to the ovarian carcinoma stage standard of International Federation of Gynecology and Obstetrics (FIGO) 2014,Ⅰ stage was in 21 cases,Ⅱ stage in 4 cases,Ⅲ stage in 2 cases,and Ⅳ stage in 1 case.The patients were followed up for 3 to 120 months,with an average of 55 months.No recurrence or metastasis was in 17 cases (FIGO Ⅰ stage 16 cases,FIGO Ⅱ stage 1 case);recurrent within 2 years was in 5 cases (FIGO Ⅱ stage 2 cases,Ⅲ stage 2 cases,Ⅳ stage 1 case),of which 4 cases died within 5 years (FIGO Ⅱ stage 1 case,Ⅲ stage 2 cases,Ⅳ stage 1 case);lost to follow-up was in 6 cases (FIGO Ⅰ stage 5 cases,FIGO Ⅱ stage 1 case).Conclusions Primary ovarian mucinous adenocarcinoma is rare,and it has no specific clinical symptoms.It is mainly characterized by fusion infiltration.Immunohistochemical result shows that CK7 is always positive,the expressions of CK20 and CDX2 are different degree,and SATB2 and PAX-8 are mostly negative.Prognosis is closely related with FIGO stage,and the patients with FIGO Ⅰ stage have good prognoses,Ⅲ and Ⅳ stage have poor prognoses.It should be distinguished from ovarian metastatic mucinous tumor.