OBJECTIVE: To investigate the biological activity and antitumor effect of pegylated recombinant human interleukin 2 (PEG-rhIL-2) obtained by site-specific conjugation of polyethylene glycol (PEG) with non-natural amino acids, and to explore its antitumor mechanism. METHODS: The binding activities of PEG-rhIL-2 at three different sites (T41, Y45, and V91) to human interleukin 2 receptors α (IL-2R_α) and β (IL-2R_β) and were detected by surface plasmon resonance (SPR) technology. Western blot was used to detect the levels of the Janus kinase-signal transducer and activator of transcription 5 (JAK-STAT5) signaling pathway activated by different doses of rhIL-2 and PEG-rhIL-2 in CTTL-2 and YT cells. Blood was collected after a single administration in mice to detect the drug concentration at different time points and evaluate the pharmacokinetic parameters of Y45-PEG-rhIL-2. Mouse hepatoma cell line Hepa1-6, pancreatic cancer cell line Pan-02, and colon cancer cell line MC-38 were selected. Tumor models were constructed in C57BL/6 mice. Different doses of Y45-PEG-rhIL-2 and excipient control were administrated respectively to evaluate the tumor suppression effect of the drug. In the MC-38 colon cancer model, the tumor suppression effect of Y45-PEG-rhIL-2 combined with anti-programmed death-1 (PD-1) monoclonal antibody was evaluated. Hepa1-6 mouse tumor models were constructed and rhIL-2, Y45-rhIL-2 and Y45-PEG-rhIL-2 were administrated respectively. The proportion of tumor-infiltrating lymphocytes was analyzed by flow cytometry. RESULTS: The SPR detection results showed that the binding activities of PEG-rhIL-2 to IL-2R_α/IL-2R_β were both reduced. The affinity of Y45-PEG-rhIL-2 to IL-2R_α was reduced to approximately 1/250, and its affinity to IL-2R_β was reduced to 1/3. Western blot results showed that the activity of Y45-PEG-rhIL-2 in stimulating JAK-STAT5 signaling in CTLL-2 cells expressing heterotrimeric IL-2 receptor complex IL-2R_αβγwas reduced to approximately 1/300, while its activity in YT cells expressing heterodimeric IL-2 receptor complex IL-2R_βγwas reduced to approximately 1/3. The pharmacokinetic evaluation after a single dose in the mice showed that the elimination half-life of Y45-PEG-rhIL-2 was 17.7 h. Y45-PEG-rhIL-2 has pharmacokinetic characteristics superior to those of rhIL-2. Y45-PEG-rhIL-2 showed dose-dependent tumor suppression activity, and the combination of Y45-PEG-rhIL-2 and anti-PD-1 antibody had a better tumor-inhibiting effect than the single use of Y45-PEG-rhIL-2 or anti-PD-1 antibody. Flow cytometry analysis demonstrated that 72 h after the administration of Y45-PEG-rhIL-2, the proportion of tumor-infiltrating cytotoxic T lymphocytes (CD8⁺T cells) increased by 86.84%. At 120 h after administration, the ratio of CD8⁺T cells to regulatory T cells (Treg) increased by 75.10%. CONCLUSION Y45-PEG-rhIL-2 obtained by site-specific conjugation via non-natural amino acids changed its receptor binding activity and inhibited tumor growth in dose-dependent manner in multiple tumor models by regulating CD8⁺T cells.
Interleukin-2/pharmacokinetics* ; Animals ; Mice ; Humans ; Recombinant Proteins/pharmacology* ; Polyethylene Glycols/chemistry* ; Cell Line, Tumor ; Antineoplastic Agents/pharmacokinetics* ; Signal Transduction/drug effects* ; STAT5 Transcription Factor/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-2 Receptor beta Subunit/metabolism*

Objective: To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies. Methods: Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed. Results: A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05). Conclusions The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:To investigate the value of musculoskeletal ultrasound examination in the evaluation of rheumatoid arthritis.Methods:A total of 89 patients with rheumatoid arthritis who received treatment in Zhejiang Rongjun Hospital from January 2020 to January 2023 were included in this study. According to the Disease Activity Score-28 for Rheumatoid Arthritis, these patients were divided into a low activity group ( n = 32), a medium activity group ( n = 36), and a high activity group ( n = 21). An additional 32 healthy controls who concurrently underwent physical examinations in Zhejiang Rongjun Hospital were included in the control group. All participants underwent a musculoskeletal ultrasound examination. Serum interleukin-1β, interleukin-6, and interleukin-23 levels were determined by an enzyme linked immunosorbent assay. Results:In the rheumatoid arthritis group, semi-quantitative scores of musculoskeletal ultrasound in terms of joint effusion, bone erosion, synovial blood flow signal, synovial hyperplasia, and total scores were (1.53 ± 0.36) points, (1.70 ± 0.45) points, (1.75 ± 0.38) points, (1.98 ± 0.42) points, and (6.97 ± 1.43) points, which were significantly higher than (0.11 ± 0.03) points, (0.14 ± 0.02) points, (0.07 ± 0.03) points, (0.15 ± 0.04) points, and (0.47 ± 0.08) points in the control group ( t = 22.23, 19.55, 24.92, 24.54, 25.63, all P < 0.05). Serum interleukin-1β, interleukin-6, and interleukin-23 levels in the rheumatoid arthritis group were (66.49 ± 15.45) ng/L, (12.33 ± 3.27) ng/L, and (206.85 ± 24.37) ng/L], which were significantly higher than (15.42 ± 4.36) ng/L, (6.58 ± 1.39) ng/L, and (124.52 ± 18.29) ng/L in the control group ( t = 18.39, 9.62, 17.41, all P < 0.05). The semi-quantitative scores of musculoskeletal ultrasound in terms of joint effusion, bone erosion, synovial blood flow signal, synovial hyperplasia, and total scores in the high activity group were significantly higher than those in the medium activity and low activity groups, and the semi-quantitative scores of musculoskeletal ultrasound in terms of joint effusion, bone erosion, synovial blood flow signal, synovial hyperplasia, and total scores in the medium activity group were significantly higher than those in the low activity group (all P < 0.05). Serum interleukin-1β, interleukin-6, and interleukin-23 levels in the high activity group were significantly higher than those in the medium activity and low activity groups, and the scores in the medium activity group were significantly higher than those in the low activity group (all P < 0.05). According to Spearman analysis, the semi-quantitative total score of musculoskeletal ultrasound was positively correlated with the severity of disease activity, interleukin-1β, interleukin-6, and interleukin-23 ( r = 0.68, 0.57, 0.52, 0.62, P < 0.05). Conclusion:Musculoskeletal ultrasound is of good value in the evaluation of rheumatoid arthritis. Musculoskeletal ultrasound results are closely related to the degree of rheumatoid arthritis and inflammatory factors.

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.

Objective:To apply the best evidence of perioperative enhanced recovery nursing for lung cancer patients to clinical practice, and to evaluate the effect of practice.Methods:Following the 5 steps of the Stetler model of research utilization, an evidence-based protocol was formed through literature search, quality assessment, evidence synthesis and revision by expert group meetings. From January to July 2021, convenience sampling was used to select 160 lung cancer patients admitted to the Thoracic Surgery of Shanghai Chest Hospital as the research object. Patients admitted from January to April 2021 were set as the control group ( n=80) for baseline review. Patients admitted from May to July 2021 were set as the intervention group ( n=80) , and an evidence-based protocol was applied. Results:Finally, one guideline and 7 consensus articles were included. The evidence-based protocol covered 10 modules of preoperative nursing assessment, nutritional management, dietary preparation, health education, postoperative dietary management, functional exercise, pipeline management, pain management, venous thrombosis management and symptom management, with a total of 22 recommendations. There were significant differences in the time of first ambulation, the completion of ambulation on the day of operation, the pain score of first ambulation, the time for the first eating, and the time for the first exhausting between the two groups ( P<0.05) . There were no complications and venous thrombosis in the two groups during hospitalization. Conclusions:The development of the evidence-based practice project is beneficial to accelerate the postoperative recovery of lung cancer patients, and is conducive to standardizing the nursing path, thereby promoting the improvement of nursing quality.

Objective:To understand the characteristics and diagnosis and treatment of brucellosis with joint pain as the first clinical manifestation, and summarize the clinical classification of brucellosis complicated with joint pain, so as to provide reference for clinical diagnosis and treatment.Methods:Cases of brucellosis with first symptom of joint pain diagnosed in the 940th Hospital of PLA Joint Logistic Support Force from January 2015 to January 2020 were selected. The main clinical features, laboratory examination, diagnosis and treatment were analyzed.Results:A total of 82 patients with joint pain of the first symptom were selected, including 61 males and 21 females. Joint pain was the main complaint of the patients, 63.4% (52/82) of the patients visited spine surgery department, 17.1% (14/82) visited minimally invasive orthopedics department, 12.2% (10/82) visited rheumatic immunology department, and 7.3% (6/82) visited traditional Chinese medicine department. Brucellosis patients with cervical lesions accounted for 22.0% (18/82), combined with lumbar lesions accounted for 51.2% (42/82). The patients with elevated C-reactive protein accounted for 68.3% (56/82), abnormal liver function accounted for 52.4% (43/82), anti "O" positive accounted for 3.7% (3/82), abnormal autoantibodies accounted for 6.1% (5/82), and human leukocyte antigen-B27 (HLA-B27) positive accounted for 12.2% (10/82). Four patients with HLA-B27 positive had sacroiliac arthritis. All patients were cured after standard and full course therapy.Conclusion:Joint pain may be the first symptom of brucellosis, and the lumbar spine and cervical spine are the most vulnerable parts.