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 explore the effect of comprehensive moxibustion with Huolong cupping in patients with lung-spleen qi deficiency type allergic rhinitis.Methods:This study was a randomized controlled trial. From October 2022 to April 2023, convenience sampling was used to select 66 patients with lung-spleen qi deficiency type allergic rhinitis who visited the Otolaryngology Head and Neck Clinic of Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine as the research subject. The patients were randomly divided into an experimental group ( n=33) and a control group ( n=33). Both groups received routine oral Chinese medicine treatment. On the basis of routine treatment, the experimental group performed comprehensive moxibustion with Huolong cupping on the meridians of the Du meridian and bladder meridian. This study compared the scores of Nasal Airway Resistance (NAR), Total Nasal Symptom Score (TNSS), Visual Analogue Scale (VAS), and Chinese version of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) between two groups of patients before and after intervention. Results:Eventually 30 patients in each of the experimental group and control group completed the study. After intervention, the NAR score of the experimental group was lower than that of the control group, and the difference was statistically significant ( P<0.05). Repeated measures analysis of variance showed that with the increase of treatment time, the TNSS, VAS, and RQLQ scores of the experimental group were lower than those of the control group with statistical differences ( P<0.05), and the time effect, inter group effect, and interaction effect were statistically significant ( P<0.05) . Conclusions:Huolong cupping comprehensive moxibustion can reduce nasal resistance, meliorate nasal symptoms and accompanying nasal symptoms, and improve the quality of life of patients.

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.

Immune checkpoint inhibitors (ICIs) exert a therapeutic effect on liver cancer by enhancing the body's anti-tumor immunity and have become an important treatment method in the field of liver cancer. However, while ICIs activate the anti-tumor immunity, they also bring a series of special toxic and side effects, i.e., immune-related adverse events (irAEs). With the wide application of ICIs, irAEs have become a major challenge in clinical practice. Such irAEs have a wide potential disease spectrum and include more than 70 different pathological states, and the most common types of irAEs associated with PD-1/PD-L1 inhibitors are skin toxicity, endocrine toxicity, pneumonia, and digestive tract toxicity, while rare irAEs include the toxicity of the central nervous system and the cardiovascular, renal, and blood systems. The wide disease spectrum of irAEs requires multidisciplinary collaborative management, and at present, many academic institutions or platforms in China and globally have formulated various guidelines for irAE management. However, the management of irAEs currently lacks the support of the results of high-level prospective trials, and the characteristics of irAEs are different from the original immune diseases of various systems; therefore, its management needs to be further optimized. This article elaborates on the epidemiology of irAEs in immunotherapy for liver cancer, related risk and predictive factors, clinical features of irAEs involving different systems, and precautions for treatment and management.

Objective:To analyze the effects of the main drug resistance mutations in the integrase (IN) region on the resistance of HIV-1 CRF01_AE strains, and compare the differences with subtype B strains.Methods:Seven IN region mutations or combined mutations (T66K, F121Y, Q148K, N155H, G118R, R263K, Q148K/N155H) were selected from the HIV drug resistance database of Stanford University in the United States, and introduced to the IN region of HIV-1 B subtype infectious clone pNL4-3 and CRF01_AE infectious clone pGX002 by seamless cloning, homologous recombination and point mutation. The mutant plasmids were transfected into 293T cells for virus packaging. The culture was expanded in MT2 cells and infectious titers were detected. Half maximal inhibitory concentrations (IC 50) of four integrase inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC), against 14 mutant viruses were detected and compared with the IC 50 against the wild-type viruses. Results:B subtype and CRF01_AE plasmids carrying seven IN region mutations or combined mutations were successfully constructed, and 14 recombinant viruses were packaged with an infectious titer of 10 4-10 6 median tissue culture infective dose (TCID 50)/ml. The recombinant viruses replicated efficiently in MT2 cells. The concentrations of HIV-1 p24 antigen contained in the supernatants of cell culture reached 830-2 700 ng/ml. Five mutations or combined mutations (T66K, F121Y, Q148K, N155H, Q148K/N155H) caused CRF01_AE and B subtype strains to be highly resistant to RAL and EVG, resulting in an increase in the IC 50 by 200 times and 2 000 times or more as compared with the IC 50 against the wild-type viruses. The same mutation-caused fold changes of IC 50 of RAL and EVG against CRF01_AE were significantly lower than that of subtype B ( P<0.01). Q148K/N155H mutation caused B subtype and CRF01_AE to be highly resistant to DTG and BIC, with IC 50 increased by more than 50 times. Other mutations had little effects on the sensitivity to DTG and BIC. Conclusions:Fourteen HIV-1 strains carrying seven INSTI resistance mutations based on B subtype and CRF01_AE were constructed. Five mutations resulted in high resistance to RAL and EVG, and there was a high level of cross-resistance. Resistance to RAL and EVG caused by the same mutation was higher in B subtype than in CRF01_AE. The combined mutation of Q148K and N155H was associated with greater resistance to DTG and BIC, indicating that the genetic barrier of DTG and BIC resistance was high. DTG and BIC could effectively inhibit the strains carrying INSTI resistance mutations without obvious subtype difference.

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.

Medicinal plant Paris L. has high medicinal value. There are 8 varietas of 4 kinds of Sect. Euthya which could be used as Chinese medicine. Sect. Euthya with stout rhizomes are the source of Chinese herb Paris L. and the core source of the medicinal plants in every place of origin. Shaanxi Province is one of the major areas. This paper summarizesand analizes the research progress of Paris L. grew in Shaanxi Province including its medicinal status, effective component, pharmacological, endophytic microorganisms sequencing, resource distribution and utilization, as well as the standardized production and planting and provides suggestions for the further research and rational exploitation and utilization of medicinal plant resources of Paris L. in Shaanxi Province.

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.