Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective:To screen the HIV standard strains with typical biological characteristics of HIV strains circulating in China through the isolation, culture, genotype and phenotype identification of HIV from the whole blood samples of HIV-infected persons, confirm genetic characteristics, traceability, and in line with the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023).Methods:Whole blood samples were collected from 48 HIV infected patients. Peripheral blood mononuclear cells (PBMCs) were isolated from the samples and co-cultured with PBMCs isolated from healthy persons′ whole blood samples to isolate and culture HIV from infected persons. We determined concentration of p24 antigen and the virus titer in the culture supernatant. The viral RNA was extracted from the successfully isolated strains, and the gag, pol genes and env C2V3 fragments of the viral genome were amplified and sequenced. The genotype, gene recombination and drug resistance sites were determined according to the viral gene sequences. Virus infection and replication were monitored by inoculating the virus culture supernatant into Ghost cells expressing CCR5 or CXCR4 to determine the viral tropism.The formation of syncytium was observed by inoculating the virus culture supernatant into MT-2 cells to determine whether was a syncytium-induced phenotype. Results:Fourteen strains with p24 antigen concentration > 1 ng/ml in culture supernatant were isolated and cultured from 48 fresh EDTA anticoagulated whole blood samples of HIV infected persons. Of the 14 strains, only one strain with a titer≥10 5 TCID 50/ml, 8 strains with titers ≥10 4 TCID 50/ml, and the other 5 strains with titers≥10 3 TCID 50/ml. Phylogenetic analysis showed that the genotypes of the strains were 9 strains of subtype B, 3 strains of CRF01_AE and 2 strains of CRF07_BC recombinant. Genotypic resistance analysis showed that 11 strains contained drug resistance sites. Ghost cells were used to verify the tropism of the strains, and it was found that 8 strains were CCR5 tropism, 6 strains were CXCR4 & CCR5 dual tropism. Only 2 of the 14 strains could induce MT-2 cytopathic effect, which was syncytium-inducing phenotype. Conclusions:Fourteen HIV strains with typical biological and genetic characteristics were isolated to screen the standard HIV strains. Among which, 1 strain was evaluated as a standard HIV strain that meets the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023). This study can also provide technical guidance for the screening of the HIV standard strains. Next step is to complete the application and reserve database construction according to the sharing mechanism of the HIV standard strains, to provide resources for the researches of HIV vaccines and drugs.

Objective:Summarize and analyze the clinical features of immune checkpoint inhibitor (ICI)-related colitis.Methods:From January 2019 to September 2020, the clinical data of 8 patients with ICI-related colitis from Peking Union Medical College Hospital were retrospectively collected and including the onset of ICI-related colitis, clinical symptoms, endoscopic and pathological findings, treatment, comorbidities and resuming of ICI. Independent sample t test was used for statistical analysis. Results:Eight patients were all male, and the median age (range) was 66 years old (55 to 74 years old), 7 cases were diagnosed with stage Ⅳ lung cancer and 1 case was diagnosed with stage Ⅲc pyelo-carcinoma. Among 8 patients, 4 cases of ICI-related colitis occurred during combination of anti-programmed death-1 (PD-1) treatment and chemotherapy, 2 cases occurred during anti-PD-1 monotherapy after combination of anti-PD-1 treatment and chemotherapy, and 2 cases occurred after anti-PD-1 monotherapy. The median time (range) was 44 d (27 to 128 d) from initial anti-PD-1 treatment to the onset of ICI-related colitis and the median time (range) was 8 d (6 to 35 d) from last anti-PD-1 treatment to onset of ICI-related colitis. The ICI efficacy of 4 patients had partial response, 2 patients had stable disease, 1 patient had disease progression, and 1 patient′s condition was not assessed. All 8 patients had moderate to severe extensive colitis. The main clinical manifestation was diarrhea (5/8), 3 patients accompanied by abdominal pain. The endoscopic findings were diffuse mucosal erosion, accompanied by ulcer in 2 patients. The main pathologic findings were cryptitis or crypt abscess, accompanied by apoptosis in 2 patients. Eight patients were all treated with glucocorticoids, among them 2 patients were further treated with biologics, due to the insufficient efficacy of glucocorticoid treatment, 4 patients had opportunistic infections. The initial prednisone dose for patients with opportunistic infections and patients without opportunistic infections was (85.00±52.60) and (60.00±23.09) mg, respectively. The prednisone treatment course was (8.75±4.03) and (7.50±3.11) weeks, respectively, and the differences were not statistically significant (both P>0.05). The colitis relapsed in all 3 patients after resuming of ICI. Conclusions:ICI-related colitis had corresponding ICI treatment history and clinical, endoscopic, and histopathological features. Glucocorticoid is the main treatment, and it is prone to relapse after resuming of ICI.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

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 first family cluster of COVID-19 in Lanzhou, so as to provide basis for improving the COVID-19 outbreak prevention capacity. Methods : On January 23, the First Hospital of Lanzhou University reported two suspected cases of COVID-19.According to the COVID-19 Epidemiological Investigation Plan ( second edition ) , general information, disease diagnosis and treatment, clinical symptoms, laboratory test results, household environment, exposure history and close contacts were collected to figure out the source of infection and routes of transmission. Results: This family cluster lasted 29 days, from January 23 to February 21, reporting nine confirmed cases ( one death ) and one asymptomatic case. There were three imported cases from Wuhan, who were the source of the cluster; and seven secondary cases, who all had close contact with the imported cases during daily life or through having dinners. The secondary attack rate was 41.18% ( 7/17 ) . Among 9 confirmed cases, the incubation period ranged from four to ten days, with a median of nine days. Except for seven secondary cases, 24 close contacts were found and detected negative in the nucleic acid tests. Conclusions The first family cluster of COVID-19 in Lanzhou is caused by the imported cases from Wuhan. All the secondary cases have had dinners and/or had contact with the imported cases, thus they are infected through respiratory droplets and close contact.

Objective: To learn the population,virus status and viral types of hantavirus（HV）hosts in Tiantai County of Zhejiang Province from 2011 to 2018,and to provide evidence for hemorrhagic fever with renal syndrome（HFRS）control. Methods: Rodents in Tiantai County were captured by night trapping method. After the species and age of rodents were identified,the composition of rodent species,dominant species and density of rodents were analyzed. The lungs and blood of rodents were sampled to detect the antigen and antibody of HV by immunofluorescence method. The HV antigen-positive lung samples were detected by RT-PCR with specific primers of HV S fragment,then HV was isolated and identified by inoculating Vero-E6 cells. Results: The average rodent density in Tiantai County from 2011 to 2018 was 4.44%. The rodent density in the field and residential areas were 4.94% and 2.23%,respectively. Ten species of rodents were identified,with Apodemus agrarius dominant in the field and Rattus norvegicus in the residential areas. Sixty-seven lung samples were HV antigen positive（4.13%）,one from Rattus norvegicus and the other sixty-six from Apodemus agrarius. Seventy-nine blood samples were HV antibody positive（4.86%）,all from Apodemus agrarius. Thirty-four HV antigen-positive lung samples were positive（50.75%）after RT-PCR amplification. Twenty-two strains of virus were isolated and all of them were from Apodemus agrarius,including twenty-one strains of Hantaan type（HTN）and one strain of Seoul type（SEO）. Conclusion In Tiantai County,Apodemus agrarius is the main source of HFRS infection;the main epidemic type of HV is HTN and SEO is first found in Apodemus agrarius.

Objective: By investigating the genotype and evolutionary variation of hantavirus (HV) in Tiantai county, a national surveillance site for hemorrhagic fever with renal syndrome (HFRS) was set in Zhejiang province, from 2011 to 2018, to reveal the molecular epidemiological characteristics of hantavirus (HV) in Tiantai. Methods: Total RNA was extracted from ultrasound treated HV antigen- positive rat lung samples in Tiantai from 2011 to 2018. After cDNA was prepared, nested PCR was used to amplify partial sequence of M fragments by using specific primers of HV. The sequences of HV in Tiantai from 2011 to 2018 were compared with other known HV sequences in order to identify the genotype and analyze the evolution and variation of the virus. Results: In 67 HV antigen-positive lung specimens, 31 were positive in nested PCR amplification with type-specific primers, including 30 Hantaan virus (HTNV) positive samples, 1 Seoul virus (SEOV) positive sample, and all the 31 samples were from Apodemus agrarius. The phylogenetic tree based on partial M segment was divided into monophyletic group, 30 strains were distributed in HTNV group and 1 was in SEOV group. The HTNV strain Tiantai T2018-130 was independently in one branch, sharing 84.8%-87.9% homology with other strains both at home and abroad, including 29 strains in HTNV group in Tiantai. The other 29 HTNV strains in Tiantai showed closer relationship. The SEOV strain T2016-31 from Apodemus agrarius showed closer relationship with previous strains of SEOV, Tiantai ZT71, ZT10 and Z37 strains of Wenzhou, Zhejiang province. Conclusions HTNV, the main genotype of HV in Tiantai of Zhejiang province, showed obvious geographic clustering, but the strain T2018-130 was distinct from the others in Tiantai. Meanwhile, by sequence analysis, we confirmed that The SEOV strain T2016-31 existed in in Apodemus agrarius, indicating there was a phenomenon of "spillover" between virus and host in SEOV evolution.

Objective To describe and compare the attitude and actual participation of decision-making regarding nursing care of patients with breast cancer, and to identify the related factors. Methods To investigate 480 cases of inpatients with breast cancer in 3 Grade ⅢA hospitals in Wuhan through questionnaire and self-designed general information questionnaire. Results There were significant differences (χ2=28.3, P<0.01) between the attitude and actual participation of decision making regarding of nursing care. The results of Logistic regression analysis showed that patients with higher education level (B=1.574, P=0.002), less children (B=-2.716, P<0.01) and higher income (B=0.323, P<0.01) , had a more active attitude to participate decision making; patients who were younger (B=-6.001, P=0.015), with higher education level (B=1.643, P=0.000), shorter duration of disease (B=-2.413, P=0.022), and lower degree of TNM stage (B=0.618, P=0.012), actually participated more often in decision making. Conclusions The actual participation was inconsistent with the attitude of decision-making regarding nursing care among patients with breast cancer. And patients′ demographic characters were related to their participation of decision making, which suggested that nurses should make a comprehensive assessment of willingness and capacity of patients′decision-making participation, identify the facilitators and barriers, and take measures to support patients to take an active part in the decision making to improve the quality of nursing care.

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.