Optimized Sugar-Free Citrus Lemon Juice Fermentation Efficiency and the Lipid-Lowering Effects of the Fermented Juice.

Aging and obesity make humans more prone to cardiovascular and metabolic syndrome diseases, leading to several serious health conditions, including hyperlipidemia, high blood pressure, and sleep disturbance. This study aimed to explore the hypolipidemic effect of fermented citrus lemon juice using a hyperlipidemic hamster model. The sugar-free lemon juice's fermentation was optimized, and the characteristics of fresh and fermented lemon juice (FLJ) were evaluated and compared, which contained polyphenols and superoxide dismutase-like activity. Results showed that the absorption and utilization efficiency of FLJ was higher compared with the unfermented lemon juice. This study's prefermentation efficiency evaluation found that 21-30 days of bacterial DMS32004 and DMS32005 fermentation of fresh lemon juice provided the best fermentation benefits, and 21-day FLJ was applied as a remedy after the efficiency compassion. After six weeks of feeding, the total cholesterol (TC) and triglyceride (TG) values in the blood and liver of the FLJ treatment groups were decreased compared with the high-fat diet (HFD) group. In addition, the blood low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced in the FLJ treatment groups compared with the HFD group. In contrast, the blood high-density lipoprotein (HDL-C) to LDL-C ratio increased considerably in the FLJ treatment groups, and the total to HDL ratio was significantly lower than in the HFD group. Compared with the HFD group, the TC content in the FLJ treatment groups' feces increased significantly. This study demonstrated that the sugar-free fermentation method and fermentation cycle management provided FLJ with the potential to regulate blood lipids. Further research and verification will be carried out to isolate specific substances from the FLJ and identify their mechanisms of action.

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer.

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.

Preliminary results of anti-vascular endothelial growth factor treatment for macular edema secondary to branch retinal vein occlusion in Lhasa Tibet / 中华眼底病杂志

Objective:To observe and evaluate the safety and efficacy of anti-vascular endothelial growth factor (VEGF) in the treatment of eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in Lhasa, Tibet.Methods:A retrospective case series. From September 2018 to January 2022, a total of 41 patients (41 eyes) with BRVO-ME, who were diagnosed in Department of Ophthalmology of Tibet Autonomous Region People’s Hospital, were included in this study. There were 21 eyes in 21 males and 20 eyes in 20 females. The median age was 53 (31,75) years. There were 24 patients with hypertension (58.8%, 24/41). Best corrected visual acuity (BCVA), ocular pressure, fundus color photography and optical coherence tomography (OCT) were performed in all eyes. The BCVA was performed using the international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The foveal macular thickness (CMT) was measured by OCT. All eyes were treated with intravitreous injection of anti-VEGF drugs, once a month, among which 23 eyes (56.1%, 23/41) received intravitreous injection of ranibizumab (IVR), and 18 eyes (43.9%, 18/41) received intravitreous injection of conbercept (IVC), and were grouped accordingly. There was no significant difference in age ( Z=-0.447), gender composition ( Z=-0.485), logMAR BCVA ( t=-1.591), intraocular pressure ( t=-0.167) and CMT ( t=-1.290) between two groups ( P>0.05). During the follow-up, the same devices and methods were used at baseline to perform relevant examinations, and the changes of BCVA, intraocular pressure, CMT and new cardiovascular and cerebrovascular events were compared between baseline and the last follow-up. logMAR BCVA, intraocular pressure and CMT were compared between baseline and last follow-up using Student t test. The comparison of injection times and follow-up time between IVR group and IVC group was conducted by Mann-Whitney U test. Results:At baseline, logMAR BCVA, intraocular pressure, and CMT were 0.852±0.431, (12.5±2.5) mm Hg (1 mm Hg= 0.133 kPa), and (578.1±191.1) μm, respectively. At the last follow-up, the number of anti-VEGF drug treatments was (2.7±1.2) times; logMAR BCVA and CMT were 0.488±0.366 and (207.4±108.7) μm, respectively, with CMT > 250 μm in 14 eyes (34.1%, 14/41). Compared with baseline, BCVA ( t=4.129) and CMT ( t=-0.713) were significantly improved, with statistical significance ( P<0.001). The injection times of IVR group and IVC group were (2.6±0.9) and (3.0±1.5) times, respectively. There were no significant differences in the number of injection times ( t=-1.275), logMAR BCVA ( t=-0.492), intraocular pressure ( t=0.351) and CMT ( t=-1.783) between the two groups ( P>0.05). No new hypertension, cardiovascular and cerebrovascular events occurred in all patients during follow-up. At the last follow-up, there were no eye complications related to treatment modalities and drugs. Conclusion:Short-term anti-VEGF treatment can improve the visual acuity of BRVO secondary ME patients and alleviate ME in Lhasa, Tibet. The safety and efficacy of ranibizumab and conbercept were similar.

Poisonous substances and geographical distribution of poisoning in hospitalized children based on data from 25 hospitals in China from 2016 to 2020 / 中华儿科杂志

Objective: To investigate the poisonous substances and geographical distribution of poisoning in children in China. Methods: A cross-sectional study. The clinical data of 8 385 hospitalized children from January 2016 to December 2020 were extracted from the FUTang Updating Medical Records database. These children aged 0 to 18 years and were admitted due to poisoning. They were grouped according to age (newborns and infants, toddlers, preschoolers, school-age children, adolescents), place of residence (Northeast China, North China, Central China, East China, South China, Southwest China, Northwest China), and mode of discharge (discharge under medical advice, transfer to another hospital under medical advice, discharge without medical advice, death, other). The poisonous substance and causes of poisoning in different groups were analyzed. Results: Among these 8 385 children, 4 734 (56.5%) were male and 3 651 (43.5%) female, with a male-to-female ratio of 1.3∶1. The age was 3 (2, 7) years. The prevalence of poisoning was 51.8% (4 343/8 385) in toddlers, 16.5% (1 380/8 385) in adolescents, 14.8% (1 242/8 385) in preschoolers, 14.4% (1 206/8 385) in school-age children, and 2.5% (214/8 385) in newborns and infants. Drug poisoning accounted for 43.5% (3 649/8 385) and pesticide accounted for 26.8% (2 249/8 385). Drug poisoning was more common in adolescents (684/1 380, 49.6%) and toddlers (2 041/4 343, 47.0%); non-drug poisoning was more common in school-age children (891/1 206, 73.9%), of which carbon monoxide was mainly in newborns and infants (41/214, 19.2%) and food poisoning in children of school age (241/1 206, 20.0%). Regarding regional characteristics, drug poisoning was more frequent in South China (188/246, 64.2%) and non-drug poisoning was more frequent in Southwest China (815/1 123, 72.5%). For drugs, anti-epileptic drugs, sedative-hypnotic drugs and anti-Parkinson's disease drugs had a higher proportion of poisoning in North China (138/1 034, 13.0%) than that in other regions. For non-drug poisoning, pesticides (375/1 123, 33.3%), food poisoning (209/1 123, 18.6%) and contact with poisonous animals (86/1 123, 7.7%) were more common in Southwest China than in other regions; carbon monoxide poisoning was more common in North China (81/1 034, 7.6%) and Northwest China (65/1 064, 6.3%). In Central China, poisoning happened more in toddlers (792/1 295, 61.2%) and less in adolescents (115/1 295, 8.8%) than in other regions. Regarding different age groups, poisoning in adolescent happened more in Northeast China (121/457, 26.5%), North China (240/1 034, 23.2%), and Northwest China (245/1 064, 23.0%). The rate of discharge under medical advice, discharge without medical advice, and mortality rate within the 5 years were 77.0% (6 458/8 385), 20.8% (1 743/8 385), 0.5% (40/8 385), respectively. Conclusions: Poisoning is more common in male and toddlers. Poisonous substances show a regional characteristic and vary in different age groups, with drugs and insecticides as the most common substances.

Diagnosis and treatment of pediatric septic shock in pediatric intensive care units from hospitals of different levels / 中华儿科杂志

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ2=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ2=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.

Occurrence of early epilepsy in children with traumatic brain injury: a retrospective study.

BACKGROUND: Early post-traumatic seizures (EPTS) refer to epileptic seizures occurring within one week after brain injury. This study aimed to define the risk factors of EPTS and the protective factors that could prevent its occurrence. METHODS: This is a single-center retrospective study in the PICU, Beijing Children's Hospital. Patients diagnosed with traumatic brain injury (TBI), admitted with and without EPTS between January 2016 and December 2020 were included in the study. RESULTS: We included 108 patients diagnosed with TBI. The overall EPTS incidence was 33.98% (35/108). The correlation between EPTS and depressed fractures is positive (P = 0.023). Positive correlations between EPTS and intracranial hemorrhage and subarachnoid hemorrhage had been established (P = 0.011and P = 0.004, respectively). The detection rates of EPTS in the electroencephalogram (EEG) monitoring was 80.00%. There was a significant difference in the EEG monitoring rate between the two groups (P = 0.041). Forty-one (37.86%, 41/108) post-neurosurgical patients were treated with prophylactic antiepileptic drugs (AEDs), and eight (19.51%, 8/41) still had seizures. No statistical significance was noted between the two groups in terms of prophylactic AEDs use (P = 0.519). Logistic regression analysis revealed that open craniocerebral injury and fever on admission were risk factors for EPTS, whereas, surgical intervention and use of hypertonic saline were associated with not developing EPTS. CONCLUSIONS: Breakthrough EPTS occurred after severe TBI in 33.98% of pediatric cases in our cohort. This is a higher seizure incidence than that reported previously. Patients with fever on admission and open craniocerebral injuries are more likely to develop EPTS.

MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1.

As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.

Changes of aqueous cytomegalovirus DNA in patients with cytomegalovirus retinitis after allogeneic bone marrow hematopoietic stem cell transplantation / 中华眼底病杂志

Objective:To observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment.Methods:A retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration.Results:At the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [ R2=0.385, P<0.000 1, B=-0.237 log 10 copies/(ml·time)], and the duration of treatment [ R2=0.394, P <0.000 1, B=-0.301 log 10 copies/(ml·week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity ( t=-1.223), intraocular pressure ( t=1.538), aqueous humor CMV-DNA load ( t=-0.109), retinitis lesion area ( Z=-0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved ( Z=-0.024) and whether the macula was involved ( Z=-1.826), combined with anterior segment inflammation ( Z =-0.499), combined with high intraocular pressure ( Z=-1.342), terminal visual acuity ( t =-0.845), intraocular pressure ( t=-0.068), total IVG times ( Z=0.907), age ( Z=-0.832), gender composition ( Z=-1.074), etc. The difference was not statistically significant ( P>0.05). Conclusion:The CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.

Clinical analysis of 6 critically ill children with acute chlorine poisoning / 中华儿科杂志

Objective: To analyze the clinical characteristics and treatment of critically ill children with acute chlorine poisoning and explore the risk factors and effective strategies. Methods: This retrospective study collected the clinical data, including general state, clinical characteristics, treatment and follow-up(till 1 year and 6 months after discharge), of 6 critically ill children who were hospitalized in the Pediatric Intensive Care Unit of Beijing Children's Hospital due to acute chlorine poisoning in August 2019. Results: There were 6 children characterized by severe dyspnea in this accident, among whom 4 were boys and two girls, aged 4-12 years. When the accident occurred, they were within 5 m of the chlorine source. These patients underwent tracheal intubation and mechanical ventilation in 3.5-7.0 h after poisoning. The child who was the closest to the chlorine source (1.5 m) and took the longest time (5 min) to evacuate was the most severe one. He suffered hypoxia which could not be corrected by conventional mechanical ventilation and severe shock, then had veno-arterial extracorporeal membrane oxygenation(ECMO) treatment started 10 h after the accident. All the 6 children in this study survived. Following-up found no growth and developmental abnormality. The pulmonary function tests were normal except for one case with increased small airway resistance due to previous suspected asthma, and the lung CT, electhoencephalogram, and brain magnetic resonance imaging were all normal. Conclusions: Severe chlorine poisoning is mainly characterized by respiratory failure. Mechanical ventilation is often required within a few hours after poisoning. When conventional mechanical ventilation is ineffective, ECMO could save live. Timely treatment could improve prognosis.

Retinal toxicity study of different-dose intravitreal ganciclovir in albino rabbit / 中华眼底病杂志

Objective:To explore safe dosage of single intravitreal injection of ganciclovir (IVG) in healthy rabit eyes, and to explore retinal toxicity of different dosage of ganciclovir after continues intravitreal injection into the vitreous cavity of healthy albino rabbit eyes.Methods:Ten healthy New Zealand albino rabbits were divided into 5 groups with 2 rabbits in each group. Each group was injected with 1 mg/0.025 ml,2 mg/0.025 ml, 5 mg/0.025 ml, 10 mg/0.025 ml ganciclovir or 0.025 ml saline (control group). After 1 week of intervention, rabbits were examined by ultra-wide-angle fundus photography, optical coherence tomography (OCT) and full field electroretinogram (ERG). The maximum mixed response of rod and cone cells (Max-R) was measured under dark adaption conditions, cone response (Cone-R) and 30 Hz flicker response (30 Hz-R) were measured under light adaption conditions. Twenty-four healthy New Zealand albino rabbits were randomly divided into a low-dose experimental group, a low-dose control group, a high-dose experimental group, and a high-dose control group, with 6 rabbits in each group, with the right eye as the experimental eye. The rabbits in the high-dose experimental group were continuously injected with ganciclovir 2 mg/0.025 ml, once a week, for a total of 4 times. The rabbits in the low-dose experimental group were injected with 1 mg/0.025 ml ganciclovir, the induction period was 2 times/week, a total of 4 times; the maintenance period was 1 time/week, a total of 2 times. The rabbits in the high-dose control group and the low-dose control group were injected with 0.025 ml normal saline into the vitreous cavity respectively. Full-field ERG examination was performed 1 day before each injection and 1 week after the last injection. Max-R was measured under dark-adapted conditions, and Cone-R and 30 Hz-R were measured under light-adapted conditions. OCT was recorded before the first injection and one week after the last injection. One week after the last injection, the experimental rabbits in each group were sacrificed for hematoxylin-eosin staining, and the retinal structure was observed under a light microscope. The comparison of a-wave and b-wave amplitude of Max-R, Cone-R and 30 Hz-R amplitude at different time was performed by two independent sample nonparametric test.Results:There were no abnormal results of fundus photography, OCT and ERG after single intravitral injection of 1 mg or 2 mg ganciclovir. One week after single 5 mg IVG, fundus photography of rabbits showed vascular occlusion and preretinal hemorrhage and ERG showed slight decrease of amplitude of Max-R, Cone-R and 30 Hz-R. One week after single 10 mg IVG, retinal necrosis and exudative changes were also observed. OCT showed edema and unclear retinal structure in the necrotic area. ERG showed significant decrease of amplitude of Max-R, Cone-R and 30 Hz-R. After continuous IVG in high dose and low-dose experimental group, the amplitude of Max-R a wave ( Z=-0.160, 0.000) and b wave ( Z=-0.321, 0.000), Cone-R a wave ( Z=-0.641,-0.641) and b wave ( Z=-0.321, -0.160), and 30 Hz-R ( Z=-0.321,-0.160) showed no difference compared to control group. No histologic evidences of retinal microstructure abnormalities were found in both groups. OCT and fundus photography before and after the intervention did not show any difference, either. Conclusion:There was no retinal toxicity of continuous 1 mg or 2 mg IVG recorded in albino rabbits.

Research status on immunotherapy trials of gastric cancer.

The breakthrough of immune checkpoint inhibitor (ICI) therapy has created extensive opportunities for cancer immunotherapy. Especially, the block of programmed death-1/programmed death ligand 1 (PD-L1) axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer (GC). However, in the past decade, single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory, including clinical trials for advanced GC. However, after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs, the objective response rate and progression-free survival of patients with gastric cancer were improved significantly. The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instability-high/mismatch repair deficiency. In this review, the updated data from the latest trial results of combination immunotherapy for GC are presented. Based on the outcome of combination therapy, we discuss its possible molecular mechanism and summarize effective predictive biomarkers. We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.

Comparison of efficacy and safety of insulin aspart injection Rishulin and NovoRapid for treatment of diabetes: a multicenter, randomized, open-labeled, controlled trial / 中华内科杂志

Objective:To compare the efficacy and safety of Tonghua Dongbao′s insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes.Methods:A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment.Results:For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% ( P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % ( P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95% CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% ( P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% ( P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L ( P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L ( P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group ( P=0.320). Ratios of negative to positive were 7.43% and 10.61% ( P=0.360), and ratios of positive to negative were 10.40% and 7.58% ( P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% ( P=0.371), and the incidence of adverse events was 76.60% and 77.70% ( P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions:Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

Comparison of the effects of different intraocular infusion solutions on histology and function of retina / 中华实验眼科杂志

Objective:To compare the effects of different intraocular infusion solutions on histology and function of retina.Methods:Human corneal endothelial cells (HCEC), human retinal pigment epithelium (HRPE) cells and rat retinal ganglion cells (RGC) were divided into normal control group, balanced saline solution (BSS) group and compound electrolyte intraocular irrigating solution (CEIIS) group, and the cells were cultured in 10% DMEM/F12 medium, BSS and CEIIS for 12, 24 and 48 hours, respectively, according to grouping.The proliferation absorbance value of cultured cells was measured by cell counting kit-8 (CCK8) method.The expression of apoptosis related proteins in cultured cells was detected by cellular immunofluorescence staining.The cell apoptosis rate and cell cycle were measured by flow cytometry.The mitochondrial damage was detected by lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) quantitative detection kit.Fifteen New Zealand white rabbits were randomly divided into control group ( n=3), BSS group ( n=6) and CEIIS group ( n=6). The left eyes were taken for vitrectomy and different intraocular perfusion fluids were used during vitrectomy according to grouping.The retinal function of operative eyes was measured by flash electroretinogram (ERG) before operation and 24 hours after operation, and the structural changes of each layer of retina were detected by optical coherence tomography (OCT). The early apoptosis of retinal cells was detected by TUNEL staining.The expressions of cytochrome C and bax protein in retina were detected by immunohistochemical staining.The ultrastructural changes of retina were observed under a transmission electron microscope.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Peking University People's Hospital (No.2019PHE059). Results:The three kinds of cultured cells in BSS and CEIIS groups were damaged in various degrees.With the extension of culture time, proliferated cells were decreased and the number of apoptotic cells was increased.Compared with the BSS group, cultured cells in the CEIIS group were dense and in orderly arrangement with uniform morphology and size.The apoptosis rates of HRPE cells and RGC in the BSS group were (37.157±6.918)% and (29.993±12.330)%, respectively, which were significantly higher than (4.163±1.310)% and (6.337±1.903)% in the CEIIS group ( P=0.003, 0.045). There was no significant difference in G0/G1+ S phase ratio of HCEC and HRPE cells among the normal control group, BSS group and CEIIS group (HCEC: F=2.226, P=0.189; HRPE: F=2.634, P=0.151), and the proportion of G2/M division arrest phase of RGC in the BSS group was significantly higher than that in the normal control group and CEIIS group ( P=0.047, 0.024). The proliferation absorbance values of HCEC, HRPE cells and RGC in the CEIIS group were significantly higher than those in the BSS group at each culture time point (all at P<0.05). The fluorescence intensity of cytochrome C, bax, caspase-3 and caspase-9 proteins in the BSS group was stronger than that in the normal control group and CEIIS group, and the fluorescence intensity of bcl-2 was weaker than that in the CEIIS group, and the fluorescence intensity of zonula occluden-1 (ZO-1) was weaker than that in the normal control group and CEIIS group.The release level of LDH in the BSS group was significantly higher than that in the CEIIS group at different time points (all at P<0.001). After 48 hours of culture, the release level of SDH in the BSS group was significantly higher than that in the CEIIS group ( P<0.05). No retinal histological abnormalities was found through OCT examination of rabbit eyes after vitrectomy in the two groups, but transmission electron microscopy showed that there were different degrees of loose arrangement of retinal photoreceptor cells, a large number of photoreceptor outer membrane discs falling off and vacuolar degeneration in the two groups, especially in the BSS group.TUNEL staining showed that the apoptotic cells were mainly located in the inner nuclear layer and RGC layer.The number of apoptotic retinal cells was (135.2±22.8)/high-power field of vision in the BSS group, which was significantly higher than (81.3±17.7)/high-power field of vision in the CEIIS group ( t=4.175, P=0.002). Full field flash ERG showed that the amplitudes of scotopic 3.0 ERG a- and b-wave in the CEIIS group after operation were significantly lower than those before operation, but the differences were not statistically significant (all at P>0.05). The amplitudes of scotopic 3.0 ERG a- and b-wave in the BSS group after operation were significantly lower than those before operation ( P=0.026, 0.010). Conclusions:In vivo and in vitro research results show that compared with BSS, there were few apoptotic cells in retinal tissue after vitrectomy perfused by CEIIS.

Systemic risk factors and epidemiology of cytomegalovirus retinitis status-post allogeneic bone marrow hematopoietic stem cell transplantation / 中华眼底病杂志

Cytomegalovirus (CMV) retinitis (CMVR) is a common opportunistic infection of the eye after allogeneic hematopoietic stem cell transplantation in patients with hematological diseases. It often occurs within 3 months after the operation, with CMV activation and high blood CMV peaks. It often occurs on patients with long-term CMV viremia, human leukocyte antigen incompatible transplantation, unrelated donor transplantation, haploid transplantation, childhood hematopoietic stem cell transplantation, delayed lymphocyte engraftment, acute and chronic graft-versus-host disease after surgery. The visual prognosis of patients is related to the area of CMVR lesions on the retina, the number of quadrants involved, whether the macula is involved, and the CMV load of the vitreous body is involved, and it is not related to whether the Epstein-Barr virus infection is combined with blood and vitreous humor. The incidence of CMVR is increasing year by year. It is helpful that paying attention to systemic risk factors and epidemiology can provide more effective guidance for ophthalmologists during diagnosis and treatment, help patients improve the prognosis of vision, and reduce or even avoid the occurrence of blindness caused by CMVR.

Measurement and analysis of corneal biological parameters from Tibetan junior middle school students in high altitude area / 中华实验眼科杂志

Objective:To measure and analyze the corneal biological parameters of Tibetan junior middle school students who have lived in Mozhugongka County of Lhasa city for a long time.Methods:A cross-sectional study was performed.The basic information including gender, age and grade of 1 784 Tibetan junior high school students who have lived in Mozhugongka County of Lhasa city for a long time was collected, and the corneal biological parameters were measured in May, 2020.The available data of 690 students were obtained in this study.Unilateral eye of each subject was randomly selected for statistical analysis using computer random number method.Three hundred and forty-five right eyes and 345 left eyes from 366 males and 324 females were included.There were 461 eyes from students aged 12 to 15 years, and 229 eyes from students aged 16 to 20 years.Sirius 3D corneal topography and anterior segment analysis system were used to measure the thinnest corneal thickness (TCT), central corneal thickness (CCT), anterior chamber depth (ACD), iridocorneal corneal angle, simulated K1 and simulated K2, thinnest point position.Histogram and Q-Q chart were used to assess the distribution of continuous variables except the thinnest point position of cornea.The differences in biological parameters were compared between males and females, 12-15 years group and 16-20 years group as well as right eyes and left eyes.The literature of corneal biological parameters from other ethnic group was reviewed and compared with the Tibetan subjects.This study complied with the Declaration of Helsinki and was approved by an Ethics Committee of Tibet Hospital (No.QZYY2019-IRBPJ-21).Results:The ACD of the right eye of the students was (3.31±0.27)mm, which was significantly greater than (3.26±0.26)mm of the left eye ( t=0.745, P=0.012). Mean TCT, CCT, iridocorneal angle, simulated K1 and simulated K2 were (504.99±30.73)μm, (509.10±35.82)μm, (47.45±5.70)°, (43.15±1.89)D, and (44.16±2.29)D of the right eye, and thoes of the left eyes were (503.34±29.22)μm, (508.36±28.75)μm, (47.86±5.88)°, (43.06±1.40)D and (44.16±1.53)D, respectively, with no significant differences between the right and left eyes (all at P>0.05). The ACD and iridocorneal angle were significantly greater, and the simulated K1 and simulated K2 were significantly smaller in males compared with females (all at P<0.05). There were no significant differences in TCT and CCT between males and females (both at P>0.05). The corneal biological parameters were not signficantly different between different age groups (all at P>0.05). The thinnest point of cornea distributed mainly at inferior temporal quadrant zone for the right eyes, and superior temporal quadrant zone for the left eyes. Conclusions:Corneal biological parameters of Tibetan junior high school students in high altitude areas might be different from those of other ethnic students.Ophthalmologists should pay attention to this population in diagnosis and treatment of corneal diseases and refractive error.

Regime for cytomegalovirus retinitis based on aqueous virology and inflammatory cytokine determination / 中华眼底病杂志

Objective To observe the safety and efficacy of regime that based on aqueous cytomegalovirus-DNA (CMV-DNA) load and IL-8 determination for therapeutic monitoring and local treatment cessation of cytomegalovirus retinitis (CMVR) patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A prospective case series study.A total of 14 CMVR patients (22 eyes) after allogeneic HSCT diagnosed in Ophthalmology Department of Peking University People's Hospital between January 2016 and December 2018 were involved in this study.All patients were CMV-DNA seronegative at baseline and were treated with intravitreous injection of ganciclovir (IVG,3 mg in 0.05 ml) twice per week for 4 times in the induction stage and once a week in the maintenance stage.Aqueous humor sample was collected during the first time of IVG every week.CMV-DNA and the level of IL-8 were measured by real time quantitative PCR and ELISA,respectively.During follow-up,negative CMV-DNA (＜ 103/ml) or level of IL-8 ＜ 30 pg/ml in aqueous sample was set as local treatment cessation.Then patients were followed every 2 weeks for at least 6 months.BCVA,intraocular pressure and fundus examination were taken for each visit.The BCVA examination was performed using the international standard visual acuity chart,which was converted into logMAR visual acuity.BCVA and intraocular pressure at the baseline and the last follow-up were compared by the Student t matching test.Results Of the 14 CMVR patients (22 eyes) after allogeneic HSCT,8 patients (16 eyes) were bilateral,6 patients (6 eyes) were unilateral.At the baseline,the mean logMAR BCVA was 0.814 ± 0.563,the intraocular pressure was 17.2 ± 7.8 mmHg (1 mmHg=0.133 kPa),the mean aqueous CMV-DNA load was (3.43 ± 4.96)× 105/ml,the mean level of IL-8 was 518 ± 541 pg/ml.At cessation of local treatment,the median number of intravitreal injections was 5 times.Nine eyes showed negative CMV-DNA in aqueous humor,of which,7 eyes showed negative IL-8 in aqueous.CMV-DNA could still be detected in 13 eyes,while IL-8 was negative.Only one eye's retinal lesion was completely quiet.Six months after local treatment cessation,the mean logMAR B CVA was 0.812 ± 0.691,the intraocular pressure was 14.8± 5.4 mmHg;which was not significantly different from baseline (t=-0.107,1.517;P=0.916,0.137).Recurrence of CMVR happened in only 1 eye because of systemic EB virus infection.Retinal lesions progressively improved and became completely quiet in all the remaining 20 eyes.In 22 eyes,iatrogenic vitreous hemorrhage occurred due to low platelet count during treatment (＜ 30 × 109/ml) in 4 eyes.When the treatment was terminated for 6 months,the fundus of hematoma absorption was clearly visible.At the time of CMVR diagnosis,there were 2 eyes (9％) with posterior subcapsular opacity,which may be caused by systemic glucocorticoid therapy after allogeneic HSCT.Conclusion Aqueous CMV-DNA load and level of IL-8 could be used as quantitative variables for monitoring the therapeutic effect and determining time for local treatment cessation for CMVR after HSCT safely and efficiently.

Construct a diagnostic thinking for intraocular inflammatory diseases / 中华眼底病杂志

The etiology of intraocular inflammatory disease and its diagnosis is complicated. Currently available and newly emerging systemic and ocular examinations are of important to determine etiology of intraocular inflammatory disorders. But there also exists multiple misunderstanding, and the strategy of their application is not well defined, or even exaggerated. Unprincipled or randomly selection of auxiliary examination would not help for etiology determination, but bring unnecessary pain and economic burden to patients. Establishment of diagnosis thinking of intraocular inflammatory disease is helpful to standardize the diagnosis process of the disease, improve the diagnostic efficiency, and relief patients from the pain and financial burden that caused by too many useless examinations.

Blood purification therapy for sepsis / 中国实用儿科杂志

Sepsis is a life-threatening organ dysfunction caused by the body's dysfunctional response to infection. There is currently no definitive symptomatic treatment for sepsis inflammatory response in the clinic. Blood purification treatment exerts immunomodulatory effects by non-specifically eliminating endotoxin and/or inflammatory mediators and shows a good prospect of application in sepsis. However,most studies on the treatment of sepsis with blood purification have not shown significant improvement in patients' prognosis. This article reviews the research progress of immunoregulation mechanism of blood purification therapy for sepsis,as well as the advantages and disadvantages of different blood purification methods.

Chinese guidelines for the assessment and provision of nutrition support therapy in critically ill children.

BACKGROUND: This document represents the first evidence-based guidelines to describe best practices in nutrition therapy in critically ill children (> 1 month and < 18 years), who are expected to require a length of stay more than 2 or 3 days in a Pediatric Intensive Care Unit admitting medical patients domain. METHODS: A total of 25,673 articles were scanned for relevance. After careful review, 88 studies appeared to answer the pre-identified questions for the guidelines. We used the grading of recommendations, assessment, development and evaluation criteria to adjust the evidence grade based on the quality of design and execution of each study. RESULTS: The guidelines emphasise the importance of nutritional assessment, particularly the detection of malnourished patients. Indirect calorimetry (IC) is recommended to estimate energy expenditure and there is a creative value in energy expenditure, 50 kcal/kg/day for children aged 1-8 years during acute phase if IC is unfeasible. Enteral nutrition (EN) and early enteral nutrition remain the preferred routes for nutrient delivery. A minimum protein intake of 1.5 g/kg/day is suggested for this patient population. The role of supplemental parenteral nutrition (PN) has been highlighted in patients with low nutritional risk, and a delayed approach appears to be beneficial in this group of patients. Immune-enhancing cannot be currently recommended neither in EN nor PN. CONCLUSION: Overall, the pediatric critically ill population is heterogeneous, and an individualized nutrition support with the aim of improving clinical outcomes is necessary and important.