OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Antibiotics are chemicals with bactericidal or bacteriostatic activity produced by microorganisms and artificially synthesized. Since the discovery of penicillin by Alexander Fleming in 1928, antibiotics have been widely used in clinical treatments as well as in the animal husbandry and aquaculture, leading to antibiotic residues in soil, water, food and other environments. At the same time, antibiotic resistance is increasingly serious, which necessitates the discovery of novel antibiotics. In recent years, with the development of synthetic biology, researchers have developed a variety of whole-cell biosensors that can respond to antibiotics. These whole-cell biosensors use microbial cells to convert antibiotic signals into readable signals, which can not only perform dynamic detection of antibiotics simply, quickly, sensitively and accurately but also effectively discover novel antibiotics. This review comprehensively summarizes the reported whole-cell biosensors for antibiotics, classifies them into two types (specific and general), and elaborates on the design principles and applications of the two types of antibiotic biosensors. This review will provide reference for the construction and application of other whole-cell biosensors for antibiotics.
Biosensing Techniques/methods* ; Anti-Bacterial Agents/pharmacology*

ObjectiveTo investigate the prevalence and its influencing factors of hyperuricemia (HUA) among the employed individuals who undergo occupational health screening in Shanghai, so as to provide a scientific basis for the prevention and control of HUA and for the health promotion in this population. MethodsCluster sampling methods were performed to recruit all the employed individuals who underwent routine health check-ups at the Shanghai Health and Medical Center from January to December 2023. Relevant data, including physical examination results, laboratory tests, and questionnaire surveys, were collected for analyses. Based on the diagnostic criteria for HUA, participants were categorized into HUA group and non-HUA group. Logistic regression analysis was used to identify the influencing factors of HUA. ResultsThe detection rate of HUA in the employed population of Shanghai was 23.26%, with a significantly higher rate in males (31.12%) than that in females (10.43%) (χ²=381.853,P<0.001). The detection rate of HUA increased with age (χ²_trend=5.728, P_trend=0.017). Logistic regression analysis revealed that males had a higher risk for HUA the females, with overweight, obesity, meat-predominant diet, hypertension, and dyslipidemia being positively correlated with HUA risk. While, individuals aged 40‒ and 50‒ years had a lower risk for HUA compared with those aged 20‒ years. ConclusionThe prevalence of HUA among the employed individuals who undergo health check-ups in Shanghai is relatively high. Attention should be paid to maintaining a healthy lifestyle and keeping a balanced diet. Targeted health management should prioritize for males, individuals with hypertension and BMI overweight and obesity, and those with dyslipidemia to reduce the risk of HUA.

OBJECTIVE To investigate the mechanism of Cistanche deserticola in the treatment of inflammatory bowel disease （IBD）. METHODS The active components of C. deserticola were screened based on TCMSP and literature reports. The targets of active ingredients were obtained via Swiss Target Prediction platform. Then the disease targets were obtained by searching GeneCards and OMIM databases. PPI network and “drug-compound-disease-target” network were constructed. The core components and core targets were screened. GO and KEGG enrichment analyses were performed， and molecular docking verification was conducted for core targets and core components. The IBD mice model was established and divided into model group， positive control group （dexamethasone， 0.4 mg/kg） and C. deserticola extract group （100， 200， 400 mg/kg）； blank control group was set， with 8 mice in each group. Each group was given relevant medicine， once a day， for 7 consecutive days. Disease activity index （DAI） score and colon length were calculated， and the pathological morphology of the colon of mice was observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， myeloperoxidase （MPO），tumor necrosis factor-α （TNF-α）] in colon tissue， and protein expressions of core targets were detected. RESULTS A total of 39 active ingredients and 232 potential targets of C. deserticola in the treatment of IBD were obtained. The treatment of IBD with C. deserticola might be related to core components such as quercetin， suchilactone， β-sitosterol and cistanoside H， and core targets such as TNF， AKT1， STAT3， EGFR and SRC. GO and KEGG pathway analysis predicted that the biological processes of C. deserticola in the treatment of IBD were mainly related to protein phosphorylation， and negative regulation of apoptosis， mainly involving PI3K/AKT and EGFR tyrosine kinase inhibitor resistance signaling pathways. The results of molecular docking showed that the binding energy between the core components and core target of C. deserticola was less than －4.7 kJ/mol. Animal experiment results showed that after intervention with C. deserticola extract， the body weight and colon length of mice significantly increased （P＜0.05 or P＜0.01）， while DAI decreased significantly （P＜0.05 or P＜0.01）. The congestion and edema of colon mucosa were significantly reduced， and the pathological score of colon tissue was significantly decreased （P＜0.05 or P＜0.01）； the levels of IL-6， IL-1β， MPO and TNF-α， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， EGFR， TNF- α， STAT3， phosphorylated STAT3 （p-STAT3）， AKT1， phosphorylated AKT1 （p-AKT1） and SRC in colon tissue were reduced significantly （P＜0.05 or P＜0.01）， while the level of IL-10 was significantly increased in model group （P＜0.01）. CONCLUSIONS C. deserticola may alleviate IBD by regulating the SRC/EGFR/PI3K/AKT signaling pathway.

Objective:To identify the strengths and weaknesses of hospital development through the application of individual scientific research performance assessment, thereby providing a basis for the formulation of science and technology policies.Methods:We established a research performance assessment system and conducted research performance assessments across the hospital for three consecutive years. The assessment results were analyzed in-depth, utilizing the Kruskal-Wallis test to determine if there were differences in the overall level of assessment scores between years and series; the Mann-Whitney test to analyze differences between the promoted and non-promoted groups; the χ2 test to analyze whether age, degree, gender, and maternity situations affected assessment grades. Results:From 2020 to 2022, the individual scientific research performance assessment scores showed an overall upward trend, with the average per capita assessment score increasing significantly from 35.26 points in 2020 to 74.04 points in 2022. There were statistical differences in the assessment scores of different professional titles, indicating that the senior professionals > the associate senior professionals > the intermediates. There was no significant difference between the promoted and non-promoted groups. Additionally, age, degree, gender, and maternity factors affected assessment grades.Conclusions:It has been preliminarily established that the assessment of individual scientific research performance can effectively steer the scientific innovation activities of researchers, and play a positive role in enhancing the overall scientific research strength. The findings from the data analysis indicate that the hospital is expected to continuously enhance its scientific research performance by focusing on newly recruited doctoral personnel, establishing a system of support and guidance, and providing preferential support to female researchers. The assessment results serve as a " benchmark" for management departments and provide data-driven insights for the development of science and technology policies.

Objective:To explore the clinical effects of free anterolateral thigh perforator flaps in repairing diabetic foot ulcers (DFUs) under a multi-disciplinary team (MDT) cooperation model.Methods:The study was a retrospective observational study. From June 2018 to December 2022, 49 DFU patients who met the inclusion criteria were admitted to the Department of Hand and Foot Microscopy and Wound Repair Surgery of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), including 28 males and 21 females, aged from 47 to 68 years, with type 2 diabetes history period ranging from 6 months to 21 years. Under a MDT cooperation model, the physicians from department of endocrinology comprehensively assessed the patients, stabilized the patients' general condition, and controlled their complications, the surgeons from department of vascular surgery assessed and improved the patients' lower limb blood supply, the physicians from department of infectious diseases provided anti-infection treatment plans, the physicians from department of anesthesiology and perioperative medicine assessed the patients' perioperative risk and ensured their perioperative safety, and according to the patients' condition, the physicians from departments such as cardiology, neurology, nutrition, and rehabilitation actively and timely participated in the treatment. The surgeons from department of hand and foot microscopy and wound repair surgery prepared the wound base and used free anterolateral thigh perforator flaps to repair the wounds. After once or multiple debridement in the first stage, the wound area ranged from 5.0 cm×4.5 cm to 17.0 cm×10.0 cm. After once or twice vacuum sealing drainage treatment, the free anterolateral thigh perforator flaps were used to repair the wounds with incision area of 6 cm×5 cm to 18 cm×11 cm in the second stage. The descending branches of lateral circumflex femoral artery and the accompanying veins of flaps were anastomosed to the arteries and veins in the recipient sites, respectively. The wounds in the flap donor sites were sutured directly. After surgery, whether the patient's perioperative period was stable, the survival of flaps, the healing of wounds in the flap donor and recipient sites were observed. During the follow-up, the texture and appearance of flaps, whether there was a new ulcer, and the patient's walking ability were observed.Results:All the patients had stable perioperative period. Among them, the flaps in 46 patients survived successfully; the flaps in 2 patients developed complete necrosis, including 1 case whose ulcer was healed after repair of pedicled flap from the lower leg, and 1 case who underwent amputation of the lower leg; the flap in 1 patient developed partial necrosis, which was healed after dressing change and skin grafting. The wounds in the flap donor and recipient sites healed well. During the postoperative follow-up of 6-24 months, the flaps had good texture and appearance with no new ulcers, and the patients had no obvious impairment in daily walk.Conclusions:The MDT cooperation model can sufficiently ensure the perioperative safety of DFU patients. The free anterolateral thigh perforator flaps can repair the DFU wounds achieving good clinical effects with high flap survival rate and decreased amputation rate.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

Objective:To develop the Cancer-associated Thrombosis (CAT) Prevention Knowledge, Attitude and Practice Questionnaire for Nurses, and conduct reliability and validity tests.Methods:This study was a questionnaire development study. Guided by the theory of knowledge, attitude, and practice, an initial CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses was formed through literature review, group discussion, two rounds of expert consultation, and pre-survey. From April to May 2023, convenience sampling was used to select 700 in-service nurses from Chinese Academy of Medical Sciences & Peking Union Medical College as the research subject, and the reliability and validity of the questionnaire were tested.Results:A total of 700 questionnaires were distributed, and 593 valid questionnaires were collected, with a valid response rate of 84.71% (593/700). The final version of the CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses included three dimensions of knowledge, attitude, and practice, with a total of 39 items. The scale-level content validity index ( S- CVI) was 1.000, with an average S- CVI of 0.971 and an item-level CVI (I- CVI) of 0.860 to 1.000. Exploratory factor analysis extracted a total of seven common factors, with a cumulative variance contribution rate of 77.376%. The total Cronbach's α coefficient of the questionnaire was 0.937, and the Cronbach's α coefficients for each dimension were 0.923, 0.987, and 0.979. The half reliability coefficient was 0.984. After two weeks, the reliability coefficients for each dimension of retesting were 0.959, 1.000, and 0.994. Conclusions:The CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses developed in this study has good reliability and validity, and can be used as an evaluation tool for the cognition of clinical nurses in CAT prevention.

Objective To compare the differences in preoperative hemoglobin changes between subtypes of Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association(AO/OTA)and Evans classifications for intertrochanteric fractures of the femur,and evaluate the feasibility of using the above two classifications to predict preoperative hemoglobin changes.Methods A total of 210 patients with hip fracture admitted to Beijing Shijingshan Hospital from October 2017 to June 2021 were selected.Baseline data,hemoglobin,use of anticoagulants before injury,intravenous fluid volume after injury,and use of low molecular weight heparin sodium after injury were collected,and hemoglobin changes among different subtypes were compared according to AO/OTA and Evans classifications of intertrochanteric fractures of the femur.Results The hemoglobin decreased in patients with intertrochanteric fractures of the femur 3 days after injury.AO/OTA classification:The 3 days after injury,hemoglobin in patients with type A1 was significantly higher than that in patients with type A2 and type A3(P<0.05),and the change of hemoglobin was significantly lower than that in patients with type A2 and type A3(P<0.05),while there was no statistically significant difference between A2 and A3(P>0.05).Evans classification:The 3 days after injury hemoglobin of type Ⅰa was significantly higher than that of type Ⅰc,type Ⅰd and type Ⅱ(P<0.05),and type Ⅰb was significantly higher than that of type Ⅰd and type Ⅱ(P<0.05).Three days after injury,the change of hemoglobin of type Ⅰa was significantly lower than that of type Ⅰc,type Ⅰd and type Ⅰ(P<0.05),type Ⅰb was significantly lower than that of type Ⅰd and type Ⅱ(P<0.05),and typeⅠc was significantly lower than that of type Ⅰd and type Ⅱ(P<0.05),while there is no statistically significant difference betweenⅠd type and Ⅱ type(P>0.05).Conclusion The decrease in hemoglobin levels within 3 days after injury in patients with intertrochanteric fractures of the femur is partially positively correlated with AO/OTA and Evans subtypes.AO/OTA classification and Evans classification may not be ideal fracture classification for predicting preoperative hemoglobin changes.