Objective To explore the clinical characteristics and risk factors of death during hospitalization in patients with community-acquired pneumonia(CAP)complicated with diabetes mellitus(DM).Methods A retrospective analysis was performed on 566 patients with CAP hospitalized in the Second Affiliated Hospital of Kunming Medical University from January 2018 to January 2022.The patients were divided into simple CAP group(n=478)and CAP combined with diabetes(CAP+DM)group(n=88)according to whether they had diabetes,and then CAP+DM group(n=88)was divided into survival group(n=69)and death group(n =19)according to whether the patients died during hospitalization.The clinical data and laboratory test indicators of patients in different groups were compared.Cox regression analysis was used to screen the risk factors of death during hospitalization in the CAP+DM group.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of independent risk factors on hospitalization death.Results Compared with the simple CAP group,the CAP+DM group had significant differences in age,concomitant hypertension,coronary heart disease,CURB-65 score,neutrophil to lymphocyte ratio(NLR),C-reactive protein(CRP),procalcitonin(PCT),albumin(ALB),prealbumin(PA),glucose(GLU),serum potassium(K),calcium(Ca),phosphorus(P),magnesium(Mg),lactic acid(Lac),non-invasive ventilation time,ICU occupancy rate and mortality rate(P<0.05);Compared with the survival group,there were statistically significant differences in CURB-65 score,NLR,CRP,PCT,GIU,ALB,PA,serum iron(Fe),Ca,non-invasive ventilation time,and ICU admission rate among the death group patients(P<0.05).Cox regression analysis showed that the increase of NLR level and the decrease in PA level were the risk factors for in-hospital death in patients with CAP complicated with diabetes(P<0.05).When the PA cutoff value was 91 mg/L,the AUC,sensitivity,and specificity for predicting in-hospital death of CAP patients with diabetes were 0.849,84.2%and 81.2%,respectively.Conclusion Patients with CAP combined with diabetes are more serious and have worse prognosis than those with CAP alone.PA has a good predictive value for the prognosis of these patients.Early detection and active intervention should be carried out to reduce the in-hospital mortality of patients.

Objective To analyze the deep venous thrombosis(DVT)after plasma infusion in a patient with congenital dysfibrinogene-mia(CD),and explore the relationship between the CD and DVT.Methods The clinical data were collected and the pedigree was investigated(3 subjects of 2 generations in total).The relevant indexes of coagulation factors of the patient and her family members were detected.The genomic DNA of peripheral blood was extracted for PCR amplification.All the exons,flanking sequences,5'and 3'untranslated regions of FGA,FGB and FGG genes of fibrinogen(Fg)of the patient were analyzed by direct sequencing.The corre-sponding mutation site was subjected to sequence in the other members of this family.The PyMol software was used to construct the pro-tein model before and after gene mutation.Results The patient was admitted to hospital for hysteromyomectomy.DVT appeared in 3 days after surgery.The prothrombin time(PT),thrombin time(TT),Fg activity(Fg∶C)and Fg antigen(Fg∶Ag)of the patient was 14.9 s,33.3 s,0.94 g/L and 2.10 g/L,respectively.The above four indicators in her mother were 14.7 s,32.8 s,0.97 g/L and 2.35 g/L,respectively.Gene sequencing revealed that both the patient and her mother had a heterozygous missense mutation c.2185G＞A(p.Glu729Lys)in exon 6 of the FGA gene.The protein model analysis demonstrated that p.Glu729Lys mutation changed the amino acid side chain and reduced the number of hydrogen bonds originally formed with Arg854.Conclusion A heterozygous missense mutation c.2185G＞A(NM_000508)in exon 6 of the FGA gene should be responsible for the low fibrinogen level in this pedigree,which might be the main reason for DVT after plasma infusion in this patient.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

Objective:To explore the effects of internet-based group cognitive-behavioral therapy(IGCBT)on the depressive and anxiety symptoms in patients with major depressive disorder(MDD).Methods:Eighty pa-tients with MDD were recruited and randomly divided into IGCBT combined drug therapy group and control group with drug therapy.Blind assessments were performed using the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)three times at baseline,4 weeks after treatment and 8 weeks after treatment,respectively.Results:The effective rates of HAMD and HAMA at the end of the 4th and 8th week,and the effective rates of HAMA at the end of the 8th week were higher in the combined treatment group than those in the control group(Ps＜0.05).The total scores of HAMD and HAMA in the combined treatment group and the control group were lower at the end of the 4th and 8th week than those at baseline(Ps＜0.001).The total scores of HAMD and HAMA were lower in the combined treatment group than those in the control group at the baseline,4 weeks and 8 weeks after treatment(Ps＜0.01).Conclusion:It suggests that intemet-based group cognitive-behavioral therapy combined with antidepressant medication has a better effect on relieving depressive and anxiety symptoms in patients with ma-jor depressive disorder than drug therapy alone,and especially has a better effect on improving anxiety symptom.

Objective:To construct recombinant influenza viruses expressing Gaussia luciferase (Gluc) with different influenza virus backbones and analyze their growth characteristics, genetic stability, ability to express Gluc and in vitro anti-influenza drug activity. Methods:The C-terminal of PR8NA was modified by inserting the porcine teschovirus-2A autocleavage peptide (P2A) and the Gluc-coding gene. Recombinant viruses, PR8NAGluc/PR8 and PR8NAGluc/WSN, were rescued using the eight-plasmid system of influenza virus reverse genetics, with seven plasmids derived from A/Puerto Rico/8/34(PR8) (H1N1) and A/WSN/1933 (WSN) H1N1. The genetic stability of the recombinant viruses was verified by RT-PCR. The fluorescence activity and the growth kinetics of the two recombinant viruses were compared. The correlation between the fluorescence activity of PR8NAGluc/WSN and median tissue culture infective dose (TCID 50), and the anti-drug activity of PR8NAGluc/WSN against oseltamivir, favipiravir, and Lianhua Qingwen in vitro were also analyzed. Results:The Gluc-expressing recombinant viruses constructed using PR8 and WSN backbones were successfully rescued by reverse genetics. Compared with the PR8 backbone, the WSN backbone significantly improved the fluorescence activity of Gluc. Moreover, the PR8NAGluc/WSN virus expressed stably in embryonated egg, and its replication kinetics was slightly lower than that of wild type. The fluorescence activity of PR8NAGluc/WSN virus had a good correlation with its TCID 50. The PR8NAGluc/WSN virus was sensitive to oseltamivir, favipiravir and Lianhua Qingwen. Conclusions:The recombinant virus with a WSN backbone exhibited higher fluorescence expression intensity as compared with the recombinant virus with a PR8 backbone. This study provided reference for high-throughput screening of anti-influenza drugs and the development of influenza virus vector vaccines.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective:To investigate the clinical features of Epstein-Barr virus associated lymphoproliferative disease in children and to improve the understanding of this disease.Methods:This study included the children with Epstein-Barr virus associated lymphoproliferative disease admitted to the First Affiliated Hospital of College of Medicine of Zhejiang University from January 2014 to December 2018.Data of these children were collected, including age, clinical manifestations, laboratory results, treatment and outcome.The clinical features and therapeutic effects were analyzed.Results:A total of 114 cases(mean age 6 years, 0~17 years)were enrolled in this study, including 53 males and 61 females.There were 107 cases(93.86%) in the mild group (38 cases of EBV infection and 69 cases of infectious mononucleosis) and 7 cases in the severe group (6.14%). Six cases of the severe group were T cell or NK cell proliferation.Compared with the mild group, the load of EBV-DNA was higher in the severe group, but there was no significant difference( χ2=0.957, P>0.05). The IgM in severe group was significantly lower( Z=-2.041, P<0.05). But the differences in the level of immune function including IgA, IgG, CD4 + cell and CD8 + cell between the severe group and the mild group were not significant.The cases in the mild group had improved after antiviral treatments.Among the severe group, 3 cases survived after treatment, another 1 case was diagnosed as hydroa vacciniforme-like EBV-related proliferative disease (HV-like LPD). After antiviral treatment, the effect was not good, then after high-dose IVIG treatment and Bortezomib combined with methylprednisolone treatment, the EBV-DNA load decreased and the condition improved.While 1 case lost to follow-up, there were 2 cases with EBV-associated hemophagocytic syndrome and 1 case with EBV-associated lymphoma died after chemotherapy or transplantation. Conclusion:EBV-associated lymphoproliferative disease may manifest as a condition similar to infectious mononucleosis.High IgE, low IgM or high DNA load may indicate poor prognosis.Immune function after EBV infection may have different effects on prognosis.When the infected lymphocyte types are NK or T cells, it may indicate poor prognosis.The efficacy of transplantation and chemotherapy in severe cases is still uncertain.

Since the Global Polio Eradication Initiative was launched by the World Health Assembly in 1988, significant progress has been made in global polio prevention and control. But the occurrence of vaccine-associated paralytic poliomyelitis cases and vaccine-derived poliovirus related cases have become a major challenge during the post-polio era. While coronavirus disease 2019(COVID-19) has brought serious disease burden and economic burden to all countries in the world, prevention and control of vaccine-preventable infectious diseases such as polio should not be neglected under the background of the global common fight against COVID-19. Taking the type Ⅲ VDPV cycle event in Shanghai as an example, the paper discussed how to do a good job of routine inoculation under the prevention and control of COVID-19 to strictly prevent the outbreak of vaccine-preventable infectious diseases.
COVID-19 ; China ; Humans ; Poliovirus ; Poliovirus Vaccine, Oral ; SARS-CoV-2 ; Vaccination

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values ( = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.

Objective:To evaluate the effects of supra-arch branches bypass on cerebral oxygen saturation and hemodynamics in patients with Stanford type B aortic dissection.Methods:From January to December 2018, consecutive 27 patients with Stanford type B aortic dissection were enrolled in the study. All patients received hybrid treatment, including supra-arch branches bypass(right axillary artery-left common carotid artery-left subclavian artery) and thoracic endovascular aortic repaire(TEVAR). All the operations were performed by the same surgical team. The left and right cerebral oxygen saturation were measured after anesthesia(T1), left carotid artery occlusion(T2) and after operation(T3); peak systolic velocity(PSV) and resistance index(RI) of left and right carotid arteries were measured before(t1) and after operation(t2).Results:The left cerebral oxygen saturation was 0.62 ±0.01, 0.54±0.01 and 0.62±0.01 at T1, T2 and T3, respectively. There was significant difference between T2 and T1 and T3( P=0.002, P=0.001), but there was no significant difference between T1 and T3. The PSV of left carotid artery at t1 and t2 were(0.91±0.11)m/s and(0.76±0.09)m/s respectively, with no significant difference( P= 0.191). The RI of left carotid artery at t1 and t2 were 0.83±0.06 and 0.93±0.13 respectively, with no significant difference( P= 0.575). Conclusion:If one side of carotid artery was blocked for a short time during supra-arch branches bypass, the cerebral oxygen saturation would be decreased temporarily, but the changes of cerebral oxygen metabolism could be completely restored after operation. However, the hemodynamics of carotid artery would not change significantly. In the hybrid treatment strategy for the patients with aortic dissection Stanford type B, blocking bilateral carotid arteries can be avoided. Making the right axillary artery-left common carotid artery-left subclavian artery shunt is a safe and effective choice.