Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

Objective To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome(NRDS)using invasive respiratory support.Methods A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital,involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS.The infants were randomly divided into a supine group(37 infants)and a prone group(40 infants).Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position,continuing in this cycle until weaning from the ventilator.The effectiveness and safety of the two approaches were compared.Results At 6 hours after enrollment,the prone group showed lower arterial blood carbon dioxide levels,inspired oxygen concentration,oxygenation index,rates of tracheal intubation bacterial colonization,and Neonatal Pain,Agitation and Sedation Scale scores compared to the supine group(P<0.05).There were no significant differences between the groups in terms of pH,arterial oxygen pressure,positive end-expiratory pressure,duration of mechanical ventilation,accidental extubation,ventilator-associated pneumonia,air leak syndrome,skin pressure sores,feeding intolerance,and grades II-IV intraventricular hemorrhage(P>0.05).Conclusions Compared to supine positioning,prone ventilation effectively improves oxygenation,increases comfort,and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS,without significantly increasing adverse reactions.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

Globally, metabolic-asssociated fatty liver disease has become a significant health burden due to its complex pathogenesis, and there are no specific and effective therapeutic drugs to date. The onset and progression of metabolic-asssociated fatty liver disease is closely associated with improper dietary habits. The cornerstone to treat metabolic-asssociated fatty liver disease is weight loss through a well-balanced diet. This article summarizes and discusses the research progress at home and abroad in relationship to metabolic-asssociated fatty liver disease and dietary patterns such as the Mediterranean diet, the DASH diet, an energy-restricted balanced diet, a low fat diet, a low carbohydrate diet, a western diet, an animal food diet, a traditional diet, and others. In addition, it categorizes the effects of various dietary patterns on the prevention, treatment, or induction of several issues that need further metabolic-asssociated fatty liver disease research for subsequent reference.
Animals ; Non-alcoholic Fatty Liver Disease/etiology* ; Diet, Fat-Restricted ; Weight Loss ; Diet, Mediterranean ; Liver

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective:To investigate the acceptance and attitude toward a novel fecal immunochemical test (FIT) in colorectal cancer screening among populations in China.Methods:From May 2018 to May 2019, 2 474 people aged 50-74 years were recruited from five provinces of China (Zhejiang, Anhui, Jiangsu, Hunan and Yunnan). The general demographic characteristics, acceptance of the new FIT technology and operational difficulties through the whole screening process were obtained through questionnaire survey. Multivariate logistic regression model was used to analyze the factors related to difficulties encountered in sampling stool, reading and uploading results.Results:The subjects were (60.0±6.4) years old, and female, high school of above educated, unemployed/retired/other, married and with medical insurance status of “new rural cooperative medical care (NRCMC)” accounted for 61.7% (1 526), 29.0%(718), 34.3% (849), 92.7% (2 293) and 31.3%(775), respectively. The population's acceptance of the FIT technology was 94.8%. In the process of FIT screening, the percentage of occurred difficulties in sampling stool, reading and uploading results were 33.1% (819), 46.4% (1 147) and 62.9% (1 557), respectively. The main difficulties were the uncertainty about whether the sampling operation was standard (28.0%), the inability to accurately judge the result displayed (32.5%) and the need for help without using a smartphone (44.2%). The results of multivariate logistic regression model analysis showed that people aged 65-74 years old and with medical insurance status of “NRCMC” were more likely to encounter difficulties in sampling, and those who were unemployed/retired/other and living with 3 or more family members were less likely to encounter difficulties in sampling. Those aged 65-74 years old, farmers or migrant workers, and those with “NRCMC” were more likely to encounter difficulties in readingresults, and those with 3 or more family members were less likely to encounter difficulties in reading result. Those with “NRCMC” were more likely to encounter difficulties in uploading results, and those with education level of high school or above, living with more than 3 family members were less likely to encounter difficulties in uploading results.Conclusion:The acceptance of the new FIT technology is relatively high among the subjects. Age, education level, occupation, number of family members living together and medical insurance status might be related to difficulties encountered in sampling stool, reading and uploading results, and it can be further strengthened in terms of the technology and characteristics of sub-populations.

Objective:To investigate the acceptance and attitude toward a novel fecal immunochemical test (FIT) in colorectal cancer screening among populations in China.Methods:From May 2018 to May 2019, 2 474 people aged 50-74 years were recruited from five provinces of China (Zhejiang, Anhui, Jiangsu, Hunan and Yunnan). The general demographic characteristics, acceptance of the new FIT technology and operational difficulties through the whole screening process were obtained through questionnaire survey. Multivariate logistic regression model was used to analyze the factors related to difficulties encountered in sampling stool, reading and uploading results.Results:The subjects were (60.0±6.4) years old, and female, high school of above educated, unemployed/retired/other, married and with medical insurance status of “new rural cooperative medical care (NRCMC)” accounted for 61.7% (1 526), 29.0%(718), 34.3% (849), 92.7% (2 293) and 31.3%(775), respectively. The population's acceptance of the FIT technology was 94.8%. In the process of FIT screening, the percentage of occurred difficulties in sampling stool, reading and uploading results were 33.1% (819), 46.4% (1 147) and 62.9% (1 557), respectively. The main difficulties were the uncertainty about whether the sampling operation was standard (28.0%), the inability to accurately judge the result displayed (32.5%) and the need for help without using a smartphone (44.2%). The results of multivariate logistic regression model analysis showed that people aged 65-74 years old and with medical insurance status of “NRCMC” were more likely to encounter difficulties in sampling, and those who were unemployed/retired/other and living with 3 or more family members were less likely to encounter difficulties in sampling. Those aged 65-74 years old, farmers or migrant workers, and those with “NRCMC” were more likely to encounter difficulties in readingresults, and those with 3 or more family members were less likely to encounter difficulties in reading result. Those with “NRCMC” were more likely to encounter difficulties in uploading results, and those with education level of high school or above, living with more than 3 family members were less likely to encounter difficulties in uploading results.Conclusion:The acceptance of the new FIT technology is relatively high among the subjects. Age, education level, occupation, number of family members living together and medical insurance status might be related to difficulties encountered in sampling stool, reading and uploading results, and it can be further strengthened in terms of the technology and characteristics of sub-populations.

OBJECTIVE: To investigate the clinical significance of tissue factor (TF) and vascular endothelial growth factor (VEGF) expression on peripheral blood CD14 positive monocytes in patients with diffuse large B cell lymphoma (DLBCL). METHODS: The expressions of TF and VEGF on peripheral CD14 monocytes in 41 patients with DLBCL (DLBCL group) before chemotherapy and after 4 chemotherapeutic courses, and in 20 healthy subjects (control group) were detected by flow cytometry respectively, meanwhile, the relationship of the expression of TF and VEGF with international prognostic indexes (IPI) and short-term effects were analysed. RESULTS: The expression levels of TF and VEGF on peripheral CD14 monocytes in DLBCL group were significantly higher than those in control group (P<0.01), and a positive correlation was found between the two groups (r=0.755, P<0.01). The expression of TF and VEGF on CD14 monocytes in patients with prognostic risk factors significantly increased as compared with those in patients without prognostic risk factors (P<0.05), but there were no significant differences of TF and VEGF expressions on CD14 monocytes in DLBCL group with different sex, age, subtypes (P＞0.05). As compared with patients without prognostic risk factors, the expression levels of TF and VEGF on CD14 monocytes of patients with prognostic risk factors significantly increased (P<0.05). The expression of TF and VEGF on CD14 monocytes in DLBCL group showed an increasing tendency along with the increase of IPI index (P<0.01). The expression levels of TF and VEGF on CD14 monocytes in remission group before chemotherapy were lower than those in non-remission group (P<0.01); after chemotherapy, the expression levels of TF and VEGF on CD14 monocytes in remission group were lower than those before chemotherapy (P<0.05), while the TF and VEGF expression levels in non-remission group were no singnificauly different from TF and VEGF levels before chemtherapy (P>0.05), the survival of patients in group with low expression of TF and VEGF was superior to that in group with high expression of TF and VEGF (P<0.05). CONCLUSION The paripheral blood CD14 monocytes in DLBCL patients highly express the TF and VEGF, which relate with IPI, therapeutic efficacy and survival, thus the TF and VEGF expression levels are of reference significance for evaluating the therapeutic efficacy and prognosis of patients.
Antineoplastic Combined Chemotherapy Protocols ; Humans ; Lipopolysaccharide Receptors ; Lymphoma, Large B-Cell, Diffuse ; Monocytes ; Prognosis ; Thromboplastin ; Vascular Endothelial Growth Factor A

One new lignan, named Z-pinnatifolin A, along with ten known analogues, were isolated from the stem bark of Syringa pinnatifolia by various chromatographic methods. Their structures were extensively determined on basis of MS and NMR spectroscopic data analyses, and comparison with those in literature. Among them, compounds 3,4, and 8-11 were isolated from this genus for the first time, and 5-7 were isolated from the specie for the first time. Compound 1 showed a moderate inhibition on NO production in BV-2 cells. The present study provides a preliminary data for clarification of bioactive ingredients of S.pinnatifolia with anti-myocardial ischemic effect.