Deep reinforcement learning-aided autonomous navigation with landmark generators.

Mobile robots are playing an increasingly significant role in social life and industrial production, such as searching and rescuing robots, autonomous exploration of sweeping robots, and so on. Improving the accuracy of autonomous navigation of mobile robots is a hot issue to be solved. However, traditional navigation methods are unable to realize crash-free navigation in an environment with dynamic obstacles, more and more scholars are gradually using autonomous navigation based on deep reinforcement learning (DRL) to replace overly conservative traditional methods. But on the other hand, DRL's training time is too long, and the lack of long-term memory easily leads the robot to a dead end, which makes its application in the actual scene more difficult. To shorten training time and prevent mobile robots from getting stuck and spinning around, we design a new robot autonomous navigation framework which combines the traditional global planning and the local planning based on DRL. Therefore, the entire navigation process can be transformed into first using traditional navigation algorithms to find the global path, then searching for several high-value landmarks on the global path, and then using the DRL algorithm to move the mobile robot toward the designated landmarks to complete the final navigation, which makes the robot training difficulty greatly reduced. Furthermore, in order to improve the lack of long-term memory in deep reinforcement learning, we design a feature extraction network containing memory modules to preserve the long-term dependence of input features. Through comparing our methods with traditional navigation methods and reinforcement learning based on end-to-end depth navigation methods, it shows that while the number of dynamic obstacles is large and obstacles are rapidly moving, our proposed method is, on average, 20% better than the second ranked method in navigation efficiency (navigation time and navigation paths' length), 34% better than the second ranked method in safety (collision times), 26.6% higher than the second ranked method in success rate, and shows strong robustness.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Comparison of the therapeutic efficacy between systemic chemotherapy with and without radiofrequency ablation for colorectal cancer liver metastases: A propensity score matching study.

OBJECTIVE: To compare therapeutic efficacy between systemic chemotherapy (SC) alone and preoperative SC followed by radiofrequency ablation (SC+RFA) in patients with colorectal cancer liver metastases (CRLM). METHODS: This study identified a cohort of patients with CRLM after treatment between 2010 and 2016. Patients who received SC+RFA were compared with SC patients by propensity score matching. Overall survival (OS) and intrahepatic progression-free survival (PFS) were compared using stratified log-rank test. The outcomes after SC and SC+RFA were also assessed in patient subgroups. RESULTS: This study identified 338 patients with CRLM who had underwent SC and had different response to chemotherapy, including non-progressive disease (non-PD) or progressive disease (PD). Of this cohort, 64 patients in SC+RFA group were matched by propensity score to 64 patients who received SC alone. Compared with SC cohort, the SC+RFA cohort yielded better OS (HR, 0.403; 95% CI, 0.271-0.601) and PFS (HR, 0.190; 95% CI, 0.113-0.320). The estimated OS rates at 1, 3 and 5 years were 93.8%, 51.6% and 15.6% for SC+RFA group and 81.3%, 26.6% and 10.9% for SC group (p＜0.001). The cumulative PFS rates at 1, 3, and 5 years were 43.8 %, 14.1% and 3.1% for the SC+RFA group and 1.6%, 0 and 0% for SC group (p＜0.0001). In subgroup analysis, compared with patients with PD response, patients with non-PD response could gain better PFS (HR, 0.207; 95% CI, 0.121-0.354) and OS (HR, 0.390; 95% CI, 0.246-0.617). CONCLUSIONS: RFA was associated with improved OS and intrahepatic PFS in CRLM patients with preoperative SC,especially in non-PD response subgroup after SC. ADVANCES IN KNOWLEDGE: The addition of RFA was advocated for CRLM patients with preoperative SC. This study will provide important reference and evidence to better perform the management of unresectable CRLM.

Sub-Tenon's bupivacaine injection is superior to placebo for pediatric strabismus surgery: A meta-analysis.

Background: The effect of post-operation sub-Tenon's bupivacaine injection for pediatric strabismus surgery is controversial. The objective of this meta-analysis is to compare the outcome of sub-Tenon injection of bupivacaine and placebo duringstrabismus surgery. Methods: We searched the databases (Pubmed, Cochrane library and EMBASE) and reference lists systematically. Randomized controlled trials (RCTs) comparing sub-Tenon's bupivacaine and placebo injection for pediatric strabismus surgery were included. The methodological quality was evaluated by the Cochrane risk of bias (ROB) tool. Outcome measurements were pain score, oculocardiac reflex (OCR), additional drug consumption and related complications. RevMan 5.4 was used for the statistical analysis and graph preparation. For the outcomes that are not suitable for statistical analysis, descriptive analysis was performed. Results: A total of 5 RCTs with 217 patients were finally identified and analyzed. Sub-Tenon's bupivacaine injection showed pain relief within 30 min after operation. But with the extension of time, the analgesic effect gradually disappeared at 1 h. It can reduce the incidence of OCR, vomiting and supplementary drug requirements. However, in terms of nausea, there is no difference between the two groups. Conclusion: Sub-Tenon's bupivacaine injection can relieve short-term postoperative pain, reduce the incidence of OCR and vomiting, and reduce the use of supplementary drugs in strabismus surgery.

Construction of iPSC-derived Inhibitory Neural Network Tissue with Synaptic Transmission Potentials / 中山大学学报(医学科学版)

ObjectiveDirected differentiation of human induced pluripotent stem cells （hiPSCs） into spinal cord γ-aminobutyric acid （GABA）-ergic progenitor cells were implanted into an decellularized optical nerve （DON） bioscaffold to construct a hiPSC-derived inhibitory neural network tissue with synaptic activities. This study aimed to provide a novel stem cell-based tissue engineering product for the study and the repair of central nervous system injury. MethodsThe combination of stepwise directional induction and tissue engineering technology was applied in this study. After hiPSCs were directionally induced into human neural progenitor cells （hNPCs） in vitro， they were seeded into a DON for three-dimensional culture， allowing further differentiation into inhibitory GABAergic neurons under the specific neuronal induction environment. Transmission electron microscopy and whole cell patch clamp technique were used to detect whether the hiPSCs differentiated neurons could form synapse-like structures and whether these neurons had spontaneous inhibitory postsynaptic currents， respectively， in order to validate that the hiPSC-derived neurons would form neural networks with synaptic transmission potentials from a structural and functional perspective. ResultsThe inhibitory neurons of GABAergic phenotype were successfully induced from hiPSCs in vitro， and maintained good viability after 28 days of culture. With the transmission electron microscopy， it was observed that many cell junctions were formed between hiPSC-derived neural cells in the three-dimensional materials， some of which presented a synapse- like structure， manifested as the slight thickness of cell membrane and a small number of vesicles within one side of the cell junctions， the typical structure of a presynatic component， and focal thickness of the membrane of the other side of the cell junctions， a typical structure of a postsynaptic component. According to whole-cell patch-clamp recording， the hiPSC-derived neurons had the capability to generate action potentials and spontaneous inhibitory postsynaptic currents were recorded in this biotissue. ConclusionsThe results of this study indicated that hiPSCs can be induced to differentiate into GABAergic progenitor cells in vitro and can successfully construct iPSC-derived inhibitory neural network tissue with synaptic transmission after implanted into a DON for three-dimensional culture. This study would provide a novel neural network tissue for future research and treatment of central nervous system injury by stem cell tissue engineering technology.

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models / 医学前沿

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

SUN Shen-tian's clinical experience in treating Tourette's syndrome with acupuncture / 中国针灸

To introduce the clinical experience of professor SUN Shen-tian in treatment of Tourette's syndrome (TS) with acupuncture. TS is a psychosomatic disease and the core pathogenesis refers to blood deficiency producing internal wind. The disease is located in the heart and liver. Acupoints are selected according to the functional orientation of the cerebral cortex. The extrapyramidal system area is preferred for tic disorder, and the emotional area is for behavioral disorder. The treatment focuses on regulating the mind by multiple methods, including manual needling technique used the transcranial repeated acupuncture, and regulating the mind by taking multiple acupoints, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Dazhong (KI 4) are stimulated. For abdominal twitching and mental symptoms of TS children, the first and third abdominal areas are selected. The target symptoms (biao) are treated specially by local acupoints, the combination of the starting and ending acupoints of the affected meridian, or the acupoints of the meridians with same name. The modified chaihu longgu muli decoction and siwu decoction are prescribed to sooth liver, nourish blood and soothe wind. In association with the characteristics and target symptoms of TS, the sequential therapy is used with filiform needling, intradermal needling, Chinese herbal medication and psychotherapy.

GAO Wei-bin's clinical experience in treatment of neurogenic bladder with acupuncture / 中国针灸

The paper introduces GAO Wei-bin's clinical experience in acupuncture treatment for neurogenic bladder. In association with the etiology, the location and types of neurogenic bladder and in accordance with nerve anatomy and meridian differentiation, the acupoints are selected accurately in treatment. Four acupoint prescriptions are allocated. For frequent urination and urinary incontinence, the foot-motor-sensory area of scalp acupuncture, Shenshu (BL 23) and Huiyang (BL 35) are used. For all kinds of urine retention, especially the patients who are not suitable for acupuncture at the lumbar region, Zhongji (CV 3), Qugu (CV 2), Henggu (KI 11) and Dahe (KI 12) are selected. For all kinds of urine retention, Zhongliao (BL 33) and Ciliao (BL 32) are applicable. For the patients with both dysuria and urinary incontinence, Zhongliao (BL 33), Ciliao (BL 32) and Huiyang (BL 35) are chosen. In treatment of neurogenic bladder, both biao (root causes) and ben (primary symptoms) are considered, as well as the accompanying symptoms; and electroacupuncture is combined accordingly. During the delivery of acupuncture, the sites where the acupoints located are detected and palpated so as to rationally control the depth of needle insertion and the operation of reinforcing and reducing needling techniques.

Transcatheter closure of rare type Ⅱ Abernethy malformation with pulmonary hypertension in children： A case report / 临床肝胆病杂志

Abernethy malformation， also known as congenital portosystemic shunts， is rare in clinical practice， with less than 300 cases reported in the global literature up to 2019. The disease can have serious complications such as pulmonary hypertension， liver tumor， and liver failure and tends to have an extremely poor prognosis， and early diagnosis and active and effective treatment can reduce and delay the onset of complications. In this case， portography combined with balloon occlusion helped to display the underdeveloped slender portal vein with dysplasia， so that the child who was formerly misdiagnosed with type Ⅰ Abernethy malformation was diagnosed with type Ⅱ Abernethy malformation， and then the child was successfully treated by transcatheter closure. This article gives a detailed report of this case.

Construction of hiPSC-derived Excitatory Neural Network-like Tissue / 中山大学学报(医学科学版)

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

High-Throughput Sequencing Technology for Detection of Gene Mutations in Myeloid Malignancies and Its Clinical Prognostic Significance / 中国实验血液学杂志

OBJECTIVE@#To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis.@*METHODS@#A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed.@*RESULTS@#In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08).@*CONCLUSION@#The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.

Development and clinical application of a new reduction device for the treatment of tibial plateau fracture under arthroscopic monitoring / 中国骨伤

OBJECTIVE@#To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy.@*METHODS@#From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria).@*RESULTS@#All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation(P<0.05).@*CONCLUSION@#The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

Quality evaluation of Commelina communis from different origins based on multicomponent content determination combined with chemometrics / 中国中药杂志

This research established a high-performance liquid chromatography(HPLC) method for simultaneous determination of isoorientin, orientin, vitexin, and isovitexin in Commelina communis to conduct content difference analysis and quality evaluation of 62 batches of C. communis from different origins. The HPLC content determination was performed on a Dikma Platisil ODS chromatographic column(4.6 mm×250 mm, 5 μm), with acetonitrile-0.1% formic acid(14∶86) as the mobile phase. The detection wavelength was set at 348 nm, the flow rate was 1.0 mL·min~(-1), and the column temperature was 35 ℃. The differences in origins and quality of 62 batches of C. communis were studied by chemometrics. The results showed that the determination of four components mani-fested a good linear relationship in the range of mass concentration(r>0.999 9), and the average recovery rate was 96.17%-103.0%. The relative standard deviations(RSDs) of precision, stability, and repeatability were all less than 2.0%. The content of four components from high to low was isoorientin>isovitexin>orientin>vitexin. Forty-seven batches of C. communis with clear origins were classified into six categories by chemometrics. C. communis from different origins had different qualities. Generally, C. communis from Western China, Central China, and South of China had superior qualities. The HPLC method established in this study is specific, simple, and efficient, which provides references for the comprehensive evaluation of the quality of C. communis. The chemometrics shows that the qualities of C. communis from different origins are largely different. Isoorientin can be used as an index to determine the content of C. communis, and its content limit should be set no less than 0.023%.

The prevalence, awareness, management and influencing factors of diabetes in middle-aged and elderly in China, evidence from the CHARLS in 2015.

Diabetes seriously affects the health of middle-aged and elderly. What we can do is to suppress the progression and avoid complications of diabetes. The aim of this study was to evaluate the prevalence, management and influencing factors in middle-aged and elderly diabetics. The data used in our study came from the follow-up survey (2015) of China Health and Retirement Longitudinal Study. After all the questionnaire data of participants was acquired, the first screening step was conducted and the participants without blood glucose or glycosylated hemoglobin test results were excluded. In the second screening step, participants without self-reported diabetes, age <45 were excluded. After data screening, STATA 16.0 software (StataCorp, USA) was used to conduct statistical analysis. Multiple logistics regression was used to analyze the influencing factors of diabetes in middle-aged and elderly. After data screening, A total of 9738 participants were enrolled in the survey of the China Health and Retirement Longitudinal Study in 2015, including diabetes 1965 and control 7773. The prevalence of diabetes in age >60 (22.20%) was significantly higher than that in age 45 to 60 (16.60%). Age, residence, physical activity, drinking, smoking and body mass index were key influencing factors according to the results of logistics regression. 46.92% diabetics were diagnosed in hospital, 22.14% were diagnosed by community medical care. 1298 among 1965 diabetes patients had standardized medication to control blood glucose, the rate was only 66.01%. The awareness rate of diabetes was only 28.75%, and the monitoring, treatment and accepting medical advice rates were 68.32%, 66.01% and 56.99% separately. The follow-up rate of diabetes was only 14.16%. Diabetes is widely prevalent in the middle-aged and elderly with the prevalence of 16.60% in the participants with age 45 to 60. The rate of self-rated diabetics underestimated the true prevalence of diabetes. Age, residence, physical activity, drinking, smoking and body mass index are key influencing factors to diabetes. Although a national diabetes health management model has been established, the awareness of diabetes was only 28.75%. Standardized diabetes registration and regular follow up should also be strictly implemented.

Multiple Mechanistic Models Reveal the Neuroprotective Effects of Diterpene Ginkgolides against Astrocyte-Mediated Demyelination via the PAF-PAFR Pathway.

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.

Population-weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study

The COVID-19 outbreak has caused enormous deaths and profound social and economic disruption globally. Accumulating evidence suggests exposure to greenspace may reduce the risk of COVID-19 mortality. Greenspace exposure enhances immune functioning, reduces inflammation, and replenishes gut microbiota may protect against the risk of mortality among those with COVID-19. However, previous studies often fail to distinguish the health effect of different types of greenspace, explore the dose-response association and optimal buffer distance, and consider the spatial dynamics of population distribution and geographic locations of greenspace. This study examined the associations among ratio of different types of greenspaces, population- weighted exposure to different types of greenspaces, and COVID-19 mortality rates using a negative binomial generalized linear mixed effects model across 3,025 counties in the United States, adjusted for socioeconomic, demographic, pre-existing chronic disease, policy and regulation, behavioral, and environmental factors. The population-weighted measure gave proportionally greater weight to greenspace near areas of higher population density. Exposure to forest and pasture was negatively associated with COVID-19 mortality rates, while developed open space has insignificant or positive associations with mortality rates. Forest outside park has the largest effect size across all buffer distances, followed by forest inside park. The optimal exposure buffer distance is 1km for forest outside park, with 1 unit of increase in exposure associated with a 9.9% decrease in mortality rates (95% confidence interval: 6.9% -12.8%). The optimal exposure buffer distance of forest inside park is 400m, with 1 unit of increase in exposure, associated with a 4.7% decrease in mortality rates (95% confidence interval: 2.4% - 6.9%). Greenspaces, especially nearby forest, may be effective at lowering the mortality risk of COVID-19 patients. Our findings suggest that policymakers and planners should prioritize forestry within walking distance of residential clusters to mitigate mortality rates during current and future respiratory pandemics.

Fibrinogen gamma-chain mutation, p.Ile171His, leads to hereditary hypofibrinogenemia / 中华内科杂志

Objective:To explore the clinical phenotype and genotype of a family with hereditary hypofibrinogenemia.Methods:Activated partial thrombin time (APTT), prothrombin time (PT),thrombin time (TT) and thrombelastogram (TEG) were tested in all family members. Fibrinogen activity and antigen were detected by Clauss method and immunoturbidimetric method respectively. All exons and flanking sequences of fibrinogen FGA,FGB,FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing.Results:The proband represented prolonged PT and TT, low Fg activity and antigen, elevated K value and decreased Angle value in TEG. Other family members reported similar changes including proband′s father,daughter and son, and his elder brother and his niece. Exon 5 c.510_512 of FGG gene in the proband revealed a minor deletion mutation.Conclusion:The novel heterozygous missense mutation of exon 5 c.510_512del (Gln170_Ile171 del ins His) of FGG gene is the molecular mechanism that leads to hereditary hypofibrinogenemia in this family.

Comparison of the detection rates of colorectal cancer liver metastasis using different MRI sequences and enhanced CT / 中华肝胆外科杂志

Objective:To study the detection rates of using different MRI sequences and enhanced CT in colorectal cancer liver metastasis (CRLM).Methods:The imaging data of CRLM patients who were treated at Peking University Third Hospital from March 2018 to September 2021 were retrospectively analyzed. Sixty-six CRLM lesions with a maximum diameter ≤10 mm were selected. Different MRI sequences such as T 1 weighted imaging (T 1WI), T 2 weighted imaging (T 2WI), diffusion weighted imaging (DWI), dynamic enhanced phase of MRI (MR-Dyn), gadolinium-etoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), enhanced hepatobiliary phase of MRI (HBP) and CT enhancement phase (CT-Dyn) were reviewed independently to determine whether the target lesions were detected. The pathological results were used as the gold standard. Paired chi-square test was used to compare the detection rate of CRLM in each group. Results:Among the 66 liver metastases, 15, 31, 55, 21, 56 and 20 were detected by T 1WI, T 2WI, DWI, MR-Dyn, HBP and CT-Dyn, respectively. Their detection rates were 22.7%, 47.0%, 83.3%, 31.8%, 84.8% and 30.3%, respectively. The detection rates of HBP and DWI were higher than those of T 2WI, MR-Dyn, CT-Dyn and T 1WI, respectively (all P<0.05). The detection rate of T 2WI was higher than that of MR-Dyn, CT-Dyn and T 1WI (all P<0.05). The detection efficiencies of non-contrast MRI and Gd-EOB-DTPA enhanced MRI for CRLM were highly consistent ( Kappa=0.745). Conclusions:The detection rates of HBP, DWI and T 2WI for CRLM were high. Non-contrast MRI could replace Gd-EOB-DTPA enhanced MRI for detection of large CRLM.

Prospects and reflections on the research and development of next-generation malaria vaccines / 中国血吸虫病防治杂志

Vaccination is one of the most effective intervention for the containment and elimination of infectious diseases. Recently, the world’s first malaria vaccine RTS, S/AS01 was approved by WHO for use among children living in moderately and highly malaria endemic areas of Africa, which brings a hope for the research and development of malaria vaccines. Here, we review the current status of malaria vaccines development and provide a perspective on the development of next-generation malaria vaccines, so as to provide insights into the successful development of malaria vaccines.