[3-O-ß-chacotriosyl glycyrrhetinic acid derivatives as potential small-molecule SARS-CoV-2 fusion inhibitors against SARS-CoV-2 entry into host cells].

OBJECTIVE: To study the inhibitory activities of 3-O-ß-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells. METHODS: With pentacyclic triterpene saponin glycyrrhizic acid (a natural SARS-CoV-2 entry inhibitor) as the lead compound, a series of 3-O-ß-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle, and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirusinfected cells. The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance (SPR) assay, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion. Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein. RESULTS: The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28 µmol/L (P < 0.05), and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus. Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S proteinmediated cell-cell fusion. Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment (S1) and fusion (S2) subunits at the 3-fold axis, where it formed multiple hydrophobic interactions with Glu309, Ser305, Arg765 and Lys964 residues with a KD value of -8.6 kcal/mol. The compound 1b at 10, 5, 2.5 and 1.25 µmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765, Lys964, Glu309 and Leu303 (P < 0.01). CONCLUSION: 3-O-ß-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane, and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

[A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou].

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

[Clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions due to atherosclerosis and dissection].

Objective: To compare the clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions caused by atherosclerosis or dissection. Methods: A retrospective cohort study. A total of 98 patients with anterior circulation tandem lesions undergoing endovascular therapy in the Wuhan NO.1 Hospital (March 2016 to March 2022) were analyzed. Median age was 64(55,71) years old, and 82.7% (81/98 cases) were males. According to the lesion etiology, the patients were divided into atherosclerosis and dissection groups. The differences in clinical outcomes between the two groups were investigated, including favorable 90-day functional outcome (modified Rankin Scale score of 0-2), successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction score of 2b-3), symptomatic intracranial hemorrhage, stroke-associated pneumonia, 90-day all-cause mortality, and average hospitalization days. Logistic regression analysis was used to adjust for potential confounders affecting functional outcomes in both groups, and to determine odds ratios and 95% confidence intervals. Results: Seventy-one patients were grouped into the atherosclerotic cause and 27 into the dissection cause cohorts. The rate of favorable 90-day functional outcome was 43.7% (31/71 cases) in the atherosclerosis group versus 55.6% (15/27 cases) in the dissection group (adjusted odds ratio=1.339; 95% confidence interval, 0.374-4.798; P=0.654). No significant differences were found in other clinical outcomes between the two groups (all P>0.05). Conclusion: The clinical prognosis of patients with tandem lesions caused by atherosclerotic stenosis or artery dissection was similar after endovascular therapy. Future studies are still needed to verify our results.

[CIC-rearranged sarcoma: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features and differential diagnosis of CIC-rearranged sarcoma (CRS). Methods: Five CRSs of 4 patients (2 biopsies of pelvic cavity and lung metastasis from case 4) diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2019 to 2021. All cases were evaluated by clinical presentation, H&E, immunohistochemical staining and molecular analysis and the related literature was reviewed. Results: There were one male and three females, the age at diagnosis ranged from 18 to 58 (mean 42.5) years. Three cases were from the deep soft tissues of the trunk and one case from the skin of foot. Grossly, the tumor size ranged from 1 to 16 cm. Microscopically, the tumor was arranged in nodules or solid sheets. The tumor cells were typically round or ovoid, with occasional spindled or epithelioid morphology. The nuclei were round to ovoid with vesicular chromatin and prominent nucleoli. Mitotic figures were brisk (>10/10 HPF). Rhabdoid cells were seen in four of five cases. Myxoid change and hemorrhage were observed in all samples and two cases showed geographic necrosis. Immunohistochemically, CD99 was variably positive in all samples, while WT1 and TLE-1 were positive in four of five samples. Molecular analysis showed CIC-rearrangements in all cases. Two patients succumbed within 3 months. One had mediastinal metastasis 9 months after surgery. One underwent adjuvant chemotherapy and remained tumor-free 10 months after diagnosis. Conclusions: CIC-rearranged sarcoma is uncommon and shows aggressive clinical course with dismal prognosis. The morphological and immunohistochemical characteristics can largely overlap with a variety of sarcomas; hence, knowledge of this entity is vital to avoid potential diagnostic pitfalls. Definitive diagnosis requires molecular confirmation of CIC-gene rearrangement.

Bilateral transfer of motor performance as a function of motor imagery training: a systematic review and meta-analysis.

Objective: The objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects. Data sources: We searched 6 online-databases (Jul-Dec 2022) using terms: "mental practice," "motor imagery training," "motor imagery practice," "mental training," "movement imagery," "cognitive training," "bilateral transfer," "interlimb transfer," "cross education," "motor learning," "strength," "force" and "motor performance." Study selection and data extraction: We selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis. Data synthesis: The meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT). Results: MIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57-0.98). The effect of MIT on BT was similar to that of PT (ES = -0.02, 95% CI = -0.15-0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57-2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74-1.17), and mixed-task (ES = 1.68, 95% CI = 1.26-2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14-0.78) and normal-task (ES = 0.56, 95% CI = 0.23-0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37-0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59-1.15). Conclusion: This review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors.

[A preliminary study on the tear matrix metalloproteinase 9 point-of-care assay using a domestic kit].

Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's Ⅰ test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.

[Study on in vitro differentiation of human adenoid-derived mesenchymal stem cells into olfactory sensory neurons].

Objective: To investigate the feasibility of isolation and culture of human adenoid-derived mesenchymal stem cells (aMSCs) in vitro, and to observe the differentiation of aMSCs into olfactory sensory neurons. Methods: Adenoid tissues surgically removed from children with adenoid hypertrophy in the Second Xiangya Hospital of Central South University from September to November of 2020 were collected. The adenoid tissues were digested and isolated by trypsin and then cultured with adhesion method. The expressions of cell surface antigens CD45, CD73 and CD90 on aMSCs of P5 generation were tested by flow cytometry, and the ability of osteogenic and adipogenic induction were used to identify cell differentiation ability. Then, aMSCs were induced into differentiation by retinoic acid (RA), sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), RA+SHH, RA+bFGF, SHH+bFGF and RA+SHH+bFGF, respectively. The morphology of differentiated cells was observed under inverted microscope. The expression of ß-tubulin 3, which was the specific marker of sensory neuron, the expressions of growth associated protein-43 (GAP43) and olfactory maker protein (OMP), which were the specific markers of olfactory sensory neuron, were detected by immunofluorescence antibody assay. The expression intensities were compared by Chi-square test of four-grid table data. Results: aMSCs were successively isolated and cultured from human adenoid tissues. P0 cells generation had good adhesion and proliferation performance. P2 cells were basically purified. P5 cells expressed CD73 and CD90 with the purity of 99.3% and 99.75% respectively, without CD45 expression. P5 cells had a good ability of osteogenic differentiation and adipogenic differentiation. Neuron-like morphology and expression of ß-tubulin 3 were found in differentiated cells after induced by RA, SHH, or bFGF, respectively. An induction of expression of GAP43 was found in differentiated cells of bFGF+SHH group and RA+SHH+bFGF group, without expression of OMP of each group. The intensity of GAP43 expression of RA+SHH+bFGF group was stronger than that of bFGF+SHH group (χ2=17.48, P<0.005). Conclusions: aMSCs can be cultured from human adenoid tissues, with the stably passaged and good differentiation ability. As a new population of mesenchymal stem cells, aMSCs have the neuroregenerative properties and could differentiate into immature olfactory sensory neurons under the induction of RA+SHH+bFGF in vitro.

[Outcomes of surgical treatment of congenital cataract with microphthalmia in infancy].

Objective: To examine the outcomes of surgical treatment for infants with congenital cataract and microphthalmia (CATM). Methods: It was a retrospective case series study. Data of 28 (55 eyes) CATM children who underwent cataract surgery at the Qingdao Eye Hospital of Shandong First Medical University and were followed up for more than 5 years between January 2010 and December 2014 under the age of 6 months. There were 15 male and 13 female children. The age at the time of surgery was (3.2±1.3) months, and the follow-up time was (8.2±1.7) years. The data included the basic information of the children, the ocular biological parameters before and after surgery and intraocular lens (IOL) implantation, and the occurrence of complications. Paired t-tests or Wilcoxon signed rank tests were used to compare groups, and logistic regression analysis was used to identify factors related to IOL implantation, secondary glaucoma, and visual axis opacification (VAO). Results: The mean preoperative axial length was (16.6±1.0) mm, and the mean horizontal corneal diameter was (9.5±0.9) mm. The axial growth rate within 2 years after the first stage of surgery was (1.4±0.8) mm/year. None of the children had an IOL implanted before the age of 2. Sixty percent of the eyes (33/55) received IOL implantation within 2 to 4 years after the first stage of surgery, while the remaining 40% (22/55) did not receive IOL implantation at the last follow-up. The axial growth rate was (0.9±0.7) mm/year within two years after the second stage of surgery. Postoperative secondary glaucoma occurred in 7 eyes (12.7%), and VAO occurred in 15 eyes (27.3%). IOL implantation was associated with preoperative axial length (OR=0.072, P<0.001) and age at the first stage of surgery (OR=7.270, P<0.001), but not with preoperative corneal diameter (P=0.735). The incidence of VAO was associated with preoperative corneal diameter (OR=4.124, P=0.011), but not with age at the first stage of surgery (P=0.489) or preoperative axial length (P=0.489). No factors related to the occurrence of secondary glaucoma were found. The best corrected visual acuity at the last follow-up after IOL implantation was (0.37±0.28) logMAR, which was better than that of children without IOL implantation (0.67±0.19) logMAR (U=49.50, P=0.003). Conclusions: Children with CATM can obtain the opportunity for IOL implantation through early surgery and ultimately achieve good visual outcomes. Properly selecting the timing for implanting IOL can keep the incidence of secondary glaucoma at an acceptable level.

Cost-effectiveness analysis of five drugs for treating postmenopausal women in the United States with osteoporosis and a very high fracture risk.

PURPOSE: Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US). METHODS: A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients. RESULTS: In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug. CONCLUSION AND RELEVANCE: Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.

[Measurement and algorithm of healthy life expectancy: a scoping review].

Objective: Healthy life expectancy (HLE), which combines life expectancy with health, is an essential comprehensive measure of life length and quality. This article aimed to systematically review the methods for defining and measuring HLE and describe application studies published, providing a reference for decision makers to select and develop methods suitable for China's conditions to measure HLE. Methods: Seven Chinese and English literature databases were searched up to May 7, 2022, and several related reviews and bibliography were manually retrieved. Systematic reviews and empirical research were included concerning HLE indicators and measurement of HLE. Information including the study area, type of the study, study population, HLE index, measurement method, data sources, and results from application studies published in the last five years were extracted. The evolution of the definition of HLE, the scope of different indicators, the measurement scale of health, and measurement methods, were all collected. Results of the empirical research related to measurement methods of indicators were summarized. The study followed the scoping review framework and was written according to the PRISMA-ScR statement. Results: A total of 84 articles were included, including 13 reviews, 17 original studies related to HLE index definition, ten original studies related to index measurement, and 44 empirical studies conducted in the past five years. There were as many as 20 indicators related to HLE, and each scale had its emphasis. A total of ten methods measuring HLE were identified, which vary in the definition of health, whether using weight, and the data type. The most commonly used indicators in the past five years were disability-free life expectancy and HLE. For the method of HLE calculation, Sullivan's method was mainly used for cross-sectional data, and the multistate life table was mainly used for longitudinal data. Conclusions: There are various definitions and measurement methods of HLE, but none are suitable for all scenarios. To summarize the HLE concept, health evaluation techniques, measurement methods, and application studies published worldwide can provide a reference for the localization of HLE measurement in China.

[The influence of lung metastasis on prognosis of previously untreated gestational trophoblastic neoplasia patients].

Objective: To investigate the impact of lung metastases on the prognosis of patients with gestational trophoblastic neoplasia (GTN). Methods: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage Ⅰ-Ⅲ GTN receiving primary chemotherapy in Peking Union Medical College Hospital between July 2014 and December 2018 were retrospectively analyzed and divided into group 1 with lung metastasis and group 2 without lung metastasis. The baseline characteristics and treatment outcomes of the two groups were compared. The optimal cut-off values of the diameter of largest lung nodule associated with recurrence were identified by receiver operating characteristic (ROC) curves. Logistic regression analyses were performed to identify risk factors for prognosis. Survival analysis was performed by Kaplan-Meier method and Log rank test. Results: Of the 381 GTN patients enrolled (216 with lung metastases and 165 without lung metastases), the pretreatment ß human chorionic gonadotrophin [median: 12 572 IU/L (1 832-51 594 IU/L) vs. 5 614 IU/L (559-26 140 IU/L), P=0.001] and FIGO score [median: 3 (1-6) vs. 2 (1-4), P=0.038] were significantly higher in patients with lung metastases than those without lung metastases. In patients with FIGO score≥5, the emergence of resistance (26.76% vs. 10.26%, P=0.036) and median number of chemotherapy courses to achieve complete remission [6 (6-8) vs. 5 (4-6), P<0.001] were significantly higher than patients with lung metastases. In patients with FIGO score 0-4, no significant difference was found in the treatment outcomes between the two groups(P=0.833). Among all patients with lung metastases, the ROC curve showed a sensitivity and specificity of 62.5% and 78.8%, respectively, for predicting recurrence when the length of the largest lung nodule was 1.6 cm, with an area under the curve (AUC) of 0.711 (95% CI: 0.550, 0.871, P=0.044). Multivariate logistic regression analysis suggested a significantly higher recurrence rate when the largest lung nodule was ≥1.6 cm (OR=7.394, 95% CI: 1.003, 54.520, P=0.049). The 1-year disease-free survival rate was significantly lower in patients with the largest lung nodule ≥1.6 cm than in patients with the nodule <1.6 cm (98.2% vs. 82.4%, P=0.001). Conclusions: Lung metastasis is associated with increased first-line chemotherapy resistance in patients with FIGO scores≥5. The diameter of the largest lung metastatic nodule ≥1.6 cm is an effective factor for predicting recurrence.

Effects of Traditional Chinese Exercises on Frailty, Quality of Life, and Physical Function on Frail and Pre-Frail Older People: A Systematic Review and Meta-Analysis.

PURPOSE: To explore the effects of traditional Chinese exercises (TCEs) on the frailty status, quality of life, and physical function of frail and pre-frail older adults. METHODS: Eight databases were searched from inception to March 28, 2022. Methodological quality and heterogeneity were assessed. Mean difference (MD) or standardized MD (SMD) were pooled using random-effects or fixed-effects meta-analysis, depending on heterogeneity. RESULTS: A total of 12 articles were included. Results showed relieved frailty status of frail and pre-frail older adults (SMD = -1.46; 95% CI [-2.39, -0.53]; p < 0.01); quality of life improved (SMD = 0.91, 95% CI [0.19, 1.63]; p < 0.01); grip strength enhanced doing Badaunjin (MD = 2.51, 95% CI [1.09, 3.93]; p < 0.01), but no significant improvement with Taichi (MD = 0.10, 95% CI [-2.3,2.5]; p = 0.93); dynamic balance ability improved (MD = -2.57, 95% CI [-2.90, -2.25], p < 0.01); 4.5-m walking time shortened (MD = -0.95; 95% CI [-1.70, -0.20]; p < 0.001); gait speed improved (MD = 0.04; 95% CI [0.01, 0.07]; p = 0.003); lower body endurance increased (MD = 33.78; 95% CI [10.99, 56.68]; p = 0.004); Lower limb flexibility improved (SMD = -2.07; 95% CI [-2.94, -1.21]; p < 0.01). CONCLUSIONS: This study showed that TCEs may be helpful in alleviating frailty status and improving the quality of life and physical functions of frail and pre-frail older adults. Lastly, additional high-quality clinical trials are warranted despite the limited strong evidence.

[Research progress on the treatment of presbyopia].

Presbyopia is a physiological aging situation that the plasticity and elasticity of the lens and the function of the ciliary muscle become weaker, resulting in a decreased accommodation and inability to focus on near objects. Nowadays, there are many clinical strategies to correct presbyopia, each of which has its own advantages and disadvantages, however, there is no true sense of way to restore accommodation function. This article reviews both worldwide and domestic research on presbyopia, and analyzes and summaries the status quo as well as research progress of presbyopia correction modalities, surgical approaches, and drug therapies, hoping to provide a reference for clinical works.

[Progress in research of determinants of healthy life expectancy].

Objective: To analyze the influencing factors of healthy life expectancy (HLE). Methods: Seven Chinese and English databases were used for the retrieval of related literatures published by May 7, 2022 to identify influencing factors of HLE, including diseases and injuries and their risk factors. Based on the ecological model of health determinants, this study classifies the risk factors of diseases and injuries into five levels: personal characteristics, individual behavior and lifestyle, social network, living and working conditions, and macroscopic socio-economic, cultural and environmental conditions. Contents of research area, HLE indicators, research population, influencing factors, data sources and results were extracted. The frequencies of reported documents of different HLE indicators and influencing factors of different dimensions were visualized by using evidence map, and the empirical studies of four authoritative English medical journals and Chinese core medical journals were further compared and described. Results: A total of 90 studies were selected, in which 26 were conducted in China (28.9%). Fifty-three studies are about diseases and injuries in the first dimension, and all of them have studied non-communicable diseases, accounting for the highest proportion (58.9%). There were 77 studies about the analysis on the determinants of health at five levels by an ecological model, all the studies reported multi-level results. Among them, 53 studies reported personal characteristics (58.9%), 47 studies reported individual behavior and lifestyle (52.2%), 10 studies reported social networks (11.1%), 35 studies reported living and working environment (38.9%), 8 studies reported social economy, culture status and environment condition (8.9%). The literatures about HLE published by 4 authoritative English medical journals and 21 Chinese core medical journals in recent three years were selected. Non-communicable diseases and personal characteristics were the top two most commonly studied factors of HLE, and 11 (52.3%) and 12 (57.1%) studies reported these two kinds of factors respectively. The most important factor contributing to the global disability-adjusted life years of non-communicable diseases was individual behavior and lifestyle, which was the most changeable factor. Conclusions: In recent three years, studies involving influencing factors of HLE were mainly non-communicable diseases and personal characteristics. In the future, individual behavior, lifestyle and working environment should be strengthened.

Effects of betaine on growth performance, intestinal health, and immune response of goslings challenged with lipopolysaccharide.

The objective of this experiment was to investigate the effects of betaine on growth performance, serum parameters, intestinal health, and immune performance of goslings in response to lipopolysaccharide (LPS) challenge. A total of 168 healthy male 15-day-old Jiangnan White Goslings were randomly divided into 4 groups, with 6 replicates per treatment and seven goslings per replicate. A 2 × 2 factorial arrangement included 2 factors, that is, LPS challenge (injection of LPS or physiological saline) and betaine (added 0 or 0.06% betaine in diet). The results indicated that LPS challenge significantly reduced the average daily feed intake (ADFI), average daily gain (ADG), and body weight (BW) at 21 D of the goslings, while dietary betaine supplementation tended to increase the ADFI during the LPS stress period (P = 0.08) and BW at 21 D of the goslings (P = 0.09). The LPS-challenged goslings showed higher pro-inflammatory cytokines (interleukin-1 [IL-1ß], interleukin-6 [IL-6], tumor necrosis factor-α (TNF-α), and Interferon-gamma [IFN-γ]) and lower anti-inflammatory cytokine (Interleukin-10 [IL-10]) (P < 0.05) at 21 D of age. Dietary betaine supplementation alleviated LPS-induced increase in pro-inflammatory cytokines. The LPS challenge significantly decreased duodenal and jejunal villus height (VH) and villus height and crypt depth ratio (VCR), while the addition of betaine significantly increased duodenal VH and VCR (P < 0.05). On the other hand, addition of betaine significantly alleviated decline of enzyme activity on lipase, amylase, trypsin, and chymotrypsin in the intestinal of goslings. The LPS challenge significantly increased the content of serum D-lactic acid (D-LA) and the activity of diamine oxidase (DAO) at 21 D of the goslings. The LPS challenge and betaine addition significantly increased the mRNA expression of Occcludin (OCLN) in jejunal mucosa at 28 D of the goslings (P < 0.05). In conclusion, our research demonstrated that betaine can alleviate the decline of growth performance and immune performance in goslings caused by LPS. The results also indicate betaine possesses anti-inflammation properties and improves intestinal barrier functions. We recommend that 0.06% betaine be added into the diet to improve the intestinal health and immune performance of goslings.

[Three cases of hemodiafiltration for the treatment of CAR-T related grade 3 - 4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors].

Objective: To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors. Methods: Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out. Results: The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months. Conclusion: HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

Safety and efficacy of extra-ventricular drainage combined with urokinase administration in the management of intraventricular hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) is a severe form of stroke. Studies of existing treatment options are controversial. Therefore, we aimed to evaluate the safety and efficacy of extra ventricular drainage (EVD) combined with uPA administration for the treatment of IVH. METHODS: The clinical data of 157 IVH patients admitted to our department during 2019-2022 were retrospectively analyzed. Based on the Glasgow Outcome Score (GOS) after 30 days, patients were categorized into favorable outcome (GOS4-5) and poor outcome (GOS1-3), and factors with prognostic impact were screened by univariate and multifactorial analysis, followed by propensity score matching and screening of paired patients for comparative analysis between the uPA and non-uPA groups. RESULTS: Patient age, uPA use, initial GCS score, and intracranial hematoma volume can all influence the patient's GOS. After propensity score-matched screening, 72 patients were finally included, 36 each in the uPA and non-uPA groups. Analysis revealed that at the follow-up after 30 days, 50.0% of patients with a GOS score of 4-5 were in the uPA group compared with 30.6% in the non-uPA group; however, they were not statistically significantly different. In contrast, the mean clearance of hematoma after four days was significantly higher in the uPA group than in the non-uPA group (P<0.05) and did not increase the incidence of postoperative complications (P>0.05). CONCLUSION: uPA treatment may eliminate hematomas faster and reduce the rate of obstruction. However, its effectiveness in improving patient prognosis does not appear to be significant. Therefore, studies with larger samples may be needed to further validate its effectiveness.

[Analysis on liver cancer mortality and cause eliminated life expectancy in key areas of 4 provinces, China, 2008-2018].

Objective: To explore the changes of liver cancer mortality and the effect of liver cancer on life expectancy in key areas of four provinces in China from 2008 to 2018 and provide the basis for the evaluation of comprehensive prevention and control of cancer and promotion of the rational allocation of health resources. Methods: Based on the national cause-of-death surveillance in key areas of the 4 provinces from 2008 to 2018, we analyzed the mortality of liver cancer, cause eliminated life expectancy (CELE) and potential gains in life expectancy (PGLEs). Software Joinpoint 4.9.0.0 was used to calculate the average annual percentage change (AAPC). Arriaga's decomposition method was used to estimate the contribution of the changes of liver cancer mortality in each age group to life expectancy. Results: The standardized mortality of liver cancer in key areas of the 4 provinces showed a downward trend from 2008 to 2018 (AAPC=-4.37%, P<0.001). The changes of liver cancer mortality had a positive effect on the increase of life expectancy, with a contribution value of 0.240 years and a contribution degree of 5.62%. The positive effect was greatest in age group 45-49 years (0.041 years, 0.96%), and the negative effect was greatest in age group 50-54 years (-0.015 years, -0.35%). Compared with 2008, the life expectancy increased by 4.27 years (AAPC=0.59%, P<0.001), the liver cancer CELE increased by 4.20 years (AAPC=0.58%, P<0.001), the PGLEs decreased by 0.07 years (AAPC=-0.62%,P<0.001), and life loss rate decreased by 0.13% (AAPC=-1.18%, P=0.001). The liver cancer PGLEs increased in Yongqiao district, Anhui province (0.09 years), and decreased in other districts (counties), with the largest decline was in Fugou county, Henan province (-0.21 years). Conclusions: From 2008 to 2018, the standardized mortality rate of liver cancer in key areas of the 4 provinces decreased gradually, contributing to the growth of life expectancy. The life loss caused by liver cancer decreased gradually, but the PGLEs varied with districts (counties).