Neurogranin as an important regulator in swimming training to improve the spatial memory dysfunction of mice with chronic cerebral hypoperfusion

Background:Vascular cognitive impairment caused by chronic cerebral hypoperfusion(CCH)has become a hot issue worldwide.Aerobic exercise positively contributes to the preservation or restoration of cognitive abilities;however,the specific mechanism has remained inconclusive.And recent studies found that neurogranin(Ng)is a potential biomarker for cognitive impairment.This study aims to investigate the underlying role of Ng in swimming training to improve cognitive impairment.Methods:To test this hypothesis,the clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(Cas9)system was utilized to construct a strain of Ng conditional knockout(Ng cKO)mice,and bilateral common carotid artery stenosis(BCAS)surgery was performed to prepare the model.In Experiment 1,2-month-old male and female transgenic mice were divided into a control group(wild-type littermate,n=9)and a Ng cKO group(n=9).Then,2-month-old male and female C57BL/6 mice were divided into a sham group(C57BL/6,n=12)and a BCAS group(n=12).In Experiment 2,2-month-old male and female mice were divided into a sham group(wild-type littermate,n=12),BCAS group(n=12),swim group(n=12),BCAS+Ng cKO group(n=12),and swim+Ng cKO group(n=12).Then,7 days after BCAS,mice were given swimming training for 5 weeks(1 week for adaptation and 4 weeks for training,5 days a week,60 min a day).After intervention,laser speckle was used to detect cerebral blood perfusion in the mice,and the T maze and Morris water maze were adopted to test their spatial memory.Furthermore,electrophysiology and Western blotting were conducted to record long-term potential and observe the expressions of Ca^(2+)pathway-related proteins,respectively.Immunohistochemistry was applied to analyze the expression of relevant markers in neuronal damage,inflammation,and white matter injury.Results:The figures showed that spatial memory impairment was detected in Ng cKO mice,and a sharp decline of cerebral blood flow and an impairment of progressive spatial memory were observed in BCAS mice.Regular swimming training improved the spatial memory impairment of BCAS mice.This was achieved by preventing long-term potential damage and reversing the decline of Ca^(2+)signal transduction pathway-related proteins.At the same time,the results suggested that swimming also led to improvements in neuronal death,inflammation,and white matter injury induced by CCH.Further study adopted the use of Ng cKO transgenic mice,and the results indicated that the positive effects of swimming training on cognitive impairments,synaptic plasticity,and related pathological changes caused by CCH could be abolished by the knockout of Ng.Conclusion:Swimming training can mediate the expression of Ng to enhance hippocampal synaptic plasticity and improve related pathological changes induced by CCH,thereby ameliorating the spatial memory impairment of vascular cognitive impairment.

3D N,O-Codoped Egg-Box-Like Carbons with Tuned Channels for High Areal Capacitance Supercapacitors

Functional carbonaceous materials for supercapacitors(SCs)without using acid for post-treatment remain a substantial challenge.In this paper,we present a less harmful strategy for preparing three-dimensional(3D)N,O-codoped egg-box-like carbons(EBCs).The as-prepared EBCs with opened pores provide plentiful channels for ion fast transport,ensure the e ective contact of EBCs electrodes and electrolytes,and enhance the electron conduction.The nitrogen and oxygen atoms doped in EBCs improve the surface wettability of EBC electrodes and provide the pseudocapacitance.Consequently,the EBCs display a prominent areal capacitance of 39.8μF cm-2(340 F g-1)at 0.106 m A cm-2 in 6 M KOH electrolyte.The EBC-based symmetric SC manifests a high areal capacitance to 27.6μF cm-2(236 F g-1)at 0.1075 m A cm-2,a good rate capability of 18.8μF cm-2(160 F g-1)at 215 m A cm-2 and a long-term cycle stability with only 1.9%decay after 50,000 cycles in aqueous electrolyte.Impressively,even in all-solid-state SC,EBC electrode shows a high areal capacitance of 25.0μF cm-2(214 F g-1)and energy density of 0.0233 m Wh cm-2.This work provides an acid-free process to prepare electrode materials from industrial by-products for advanced energy storage devices.

Interconnected carbon nanocapsules with high N/S co-doping as stable and high-capacity potassium-ion battery anode

Carbonaceous materials have drawn much attention in potassium-ion batteries (PIBs) due to their low price and superior physicochemical properties. However, the application of carbonaceous materials in PIB anodes is hindered by sluggish kinetics and large volume expansion. Herein, N/S co-doped carbon nanocapsule (NSCN) is constructed for superior K+ storage. The NSCN possesses 3D nanocapsule framework with abundant meso/macropores, which guarantees structural robustness and accelerates ions/electrons transportation. The high-level N/S co-doping in carbon matrix not only generates ample defects and active sites for K+ adsorption, but also expands interlayer distance for facile K+ intercalation/deintercalation. As a result, the NSCN electrode delivers a high reversible capacity (408 mAh g^(−1) at 0.05 A g^(−1)), outstanding rate capability (149 mAh g^(−1) at 5 A g^(−1)) and favorable cycle stability (150m Ah g^(−1) at 2 A g^(−1) after 2000 cycles). Ex situ TEM, Raman and XPS measurements demonstrate the excellent stability and reversibility of NSCN electrode during potassiation/depotassiation process. This work provides inspiration for the optimization of energy storage materials by structure and doping engineering.

Pillar effect boosting the electrochemical stability of Prussian bluepolypyrrole for potassium ion batteries

Due to the high theoretical capacity and electrode potential,Prussian blue is regarded as promising cathode material for potassium ion batteries.However,inferior structural stability,poor electronic conductivity,ambiguous energy storage mechanism have limited the application of Prussian blue materials.Herein,a highly stable Prussian blue-polypyrrole(PB-PPY)composite has been prepared by a facile one-step method.PB-PPY displays higher discharging capacity,better rate capacity,and longer cycling lifespan than that of pure Prussian blue in potassium ion batteries.The superior electrochemical performance can be attributed to the unique synthesis strategy to reduce the content of vacancies and crystal water in Prussian blue and enhance the conductivity.Furthermore,partial K ions have been evidenced that could remain in the Prussian blue framework,which contributes the long-term cycling stability.The K ions in the framework play the role of“pillars”to support the framework of Prussian blue and relieve the structural stress during the intercalation and de-intercalation of K ions.This work will reveal a new energy storage mechanism of Prussian blue and promote the design of high stability Prussian blue in the future.

Evaluating Tislelizumab, Lenvatinib, and FOLFOX4-HAIC as a Conversion Therapy for Unresectable Hepatocellular Carcinoma

Background and aims:Conversion therapy downstages tumors and renders patients with unresectable hepatocel-lular carcinoma(HCC)eligible for radical resection.This study aimed to evaluate the efficacy and safety of tislelizumab plus lenvatinib and hepatic artery infusion chemotherapy with oxaliplatin,fluorouracil,and leuco-vorin(FOLFOX4-HAIC)as a first-line conversion therapy.Methods:Clinical data from HCC patients who were treated with the triple therapy between April 2021 and April 2022 were retrospectively analyzed.The primary outcome included objective response rate(ORR),disease control rate(DCR),conversion resection rate(CRR),and treatment-related adverse events(TRAEs).Results:A total of 18 patients completed conversion therapy assessment,which ended on March 27,2023.The patients had a median age of 55.5(37–72)years,and 94.4%were male.According to mRECIST,tumor shrinkage was observed in all patients,with an ORR of 94.4%(17/18),a DCR of 94.4%(17/18),and a median time to response of 1.4(0.7–3.0)months.Successful conversion was observed in 61.1%(11/18)of patients(mRECIST).The CRR and pathological complete response were 38.9%(7/18)and 57.1%(4/7),respectively.The median progression-free survival(PFS)was 17.8 months,while median overall survival was not reached.The 6-and 9-month PFS rates were 83.3%and 66.7%,respectively.The most common TRAE(16/18 patients,88.9%)was an increase in aspartate aminotransferase levels.Conclusion:Tislelizumab combined with lenvatinib and FOLFOX4-HAIC achieved a high conversion rate and acceptable toxicity in patients with unresectable HCC,suggesting that this combination may represent a new conversion strategy for this population.

Clinical features of adult spinal muscular atrophy:46 cases

BACKGROUND： Spinal muscular atrophy （SMA） is a kind of degenerative disease of nervous system. There are 4 types in clinic, especially types Ⅰ, Ⅱ and Ⅲ are common, and the researches on those 3 types are relative mature. Type IV is a kind of adult spinal muscular atrophy （ASMA）, which has low incidence rate and is often misdiagnosed as amyotrophic lateral sclerosis, muscular dystrophy, cervical syndrome, or others.OBJEETIVE： To observe the clinical features of 46 ASMA patients and analyze the relationship between course and activity of daily living. DESIGN ： Case analysis.SETTING： Departments of Neurology of the 81 Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIPANTS ： A total of 46 ASMA patients were selected from the Departments of Neurology of the 81 Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA between April 1998 and January 2002. All patients were consentient. Among 46 cases, there were 37 males and 9 females with the mean age of 42 years. The patients＇ courses in all ranged from 6 months to 23 years, concretely, courses of 37 cases were less than or equal to 5 years, and those of 9 cases were more than or equal to 6 years.METHODS： ① All the 46 ASMA patients were asked to check blood sedimentation, anti O, serum creatinine, creatine, blood creatine phosphokinase （CPK） and muscular biopsy as early as possible. ②X-ray was used to measure plain film of cervical vertebra borderline film of cranium and neck at proximal end of upper limb of 25 cases and plain film of abdominal vertebra at proximal end of lower limb of 17 cases. ③ Cerebrospinal fluid of lumbar puncture was checked on 42 cases, for routine examination, biochemical examination, and immunoglobulin examination. Electromyogram （EMG） was also examined to 42 cases. ④ Barthel index was used to evaluate activities of daily living （ADL） of patients with various courses. The index ranged from 1 to 100. The more the index of a ASMA was, the stronger his independence was. ⑤ The Barthel indexes of patients with courses ≤ 5 years and those ≥ 6 years were compared with univariate analysis of variance. MAIN OUTCOME MEASURES： ① Incidences of all patients at the first time; ② values of relative blood and blood biochemistry; ③results of muscular biopsy; ④ results of EMG and relative X-ray plain film of 42 cases; ⑤ results of cerebrospinal fluid of 42 cases; ⑥ comparisons of Barthel index of patients with various courses.RESULTS： A total of 46 ASMA patients were involved in the final analysis. ① Incidence on the first time： 25 patients had the disease at the proximal end of upper limb, 17 at the proximal end of lower limb, and 4 at the four limbs. ② Value of serum-blood CPK of one fourth patients was increased slightly （3.034-9.735 μkat/L; normal value： 0.400-3.001 μkat/L）, and other values of blood and blood biochemical indicator were normal. ③Results of muscle biopsy of all patients showed that a small group of muscular atrophy could be observed mostly, and muscle group in the same type and compensatory hypertrophy of muscle fibres were also observed with ATP enzyme staining. ④ Results of EMG of 42 cases suggested that 37 patients had mild and moderate nerve-derived injury and 3 had mild muscle-derived injury. Results of all the X-ray plain films in this study were normal. ⑤ Results of routine, biochemical and immunoglobulin examination in cerebrospinal fluid of lumbar puncture in 42 cases were all normal. ⑥The difference between Barthel indexes of patients with courses ≤ 5 years and those ≥ 6 years was not significant [（64.73±20.38） vs （68.89±21.76） points, P〉 0.05]. CONCLUSION ： ① Amyasthenia is mainly occurred at the proximal end of the four limbs of ASMA patients. A small group of muscular atrophy is its mostly pathological change, and the progression of the disease is slow. ② Most patients have mild and moderate nerve-derived injury under EMG examination.③ The duration of a patient suffered from the disease has no obvious effect on his ADL ability.

Expert consensus on prevention and cardiopulmonary resuscitation for cardiac arrest in COVID-19

Background:Cardiopulmonary resuscitation(CPR)strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest.During CPR,both healthcare and non-healthcare workers who provide resuscitation are at risk of infection.The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients.Main recommendations:1)A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs.2)Psychological counseling and treatment are highly recommended,since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest.3)Healthcare workers should wear personal protective equipment(PPE).4)Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19.5)Hands-only chest compression and mechanical chest compression are recommended.6)Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early.7)CPR should be provided for 20-30 min.8)Various factors should be taken into consideration such as the interests of patients and family members,ethics,transmission risks,and laws and regulations governing infectious disease control.Changes in management:The following changes or modifications to CPR strategy in COVID-19 patients are proposed:1)Healthcare workers should wear PPE.2)Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols.3)Both the benefits to patients and the risk of infection should be considered.4)Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Identification of positive cofactor 4 as a diagnostic and prognostic biomarker associated with immune infiltration in hepatocellular carcinoma

Background and aims:Human positive cofactor 4(PC4)is associated with the development and therapeutic resistance of several malignancies.However,the role of PC4 in hepatocellular carcinoma(HCC)remains obscure.Methods:The expression status of PC4 was explored in Gene Expression Omnibus and The Cancer Genome Atlas datasets.Subsequently,the prognostic and diagnostic significance of PC4 in HCC patients was analyzed.Functional enrichment analyses were conducted to explore biological functions and potential mechanisms.The CIBERSORT algorithm was used for immune infiltration analysis.The risk signature was constructed by LASSO-Cox regression and was validated with the International Cancer Genome Consortium dataset.Quantitative real-time polymerase chain reaction was used to verify the expression levels of all genes.Tumor Immune Dysfunction and Exclusion analysis evaluated immunotherapy response.Finally,using online databases,PC4-related competing endogenous RNA networks were constructed.Results:PC4 levels were significantly upregulated in HCC and positively correlated with the pathological grade and clinical stage.The PC4-high expression group showed worse prognosis.In addition,PC4 could distinguish between tumor and normal tissues with an area under the curve of 0.965.The PC4 level was associated with immune checkpoints and immune cell infiltration.In the training and validation sets,the eight-gene risk signature strongly correlated with HCC patient prognosis.Tumor Immune Dysfunction and Exclusion analysis showed that patients in both the PC4-low and low-risk groups were more likely to benefit from immunotherapy.Finally,an lncRNA/microRNA-101-3p/PC4 network was constructed.Conclusion:We confirmed PC4 as a diagnostic and prognostic biomarker in HCC patients.We also developed and validated an eight-gene risk signature,which will help in clinical decision-making.The competing endogenous RNA network could help explore the regulatory mechanisms of PC4 in HCC.

Promoting rapid development of Chinese minimally invasive medicine journals

In recent years,the development of Chinese scientific journals does not match the scientific development in China,especially in the field of minimally invasive surgery medicine.Scientific journals of minimally invasive medicine in China face competition not only from other traditional journals at home and abroad,but also from new media.Journals of minimally invasive medicine should be more creative,find innovative business solutions,attract professional manuscripts,and even incentivize people to contribute to projects.By doing so,we can constantly improve journals'influence,transmission,guidance and credibility in step with the pace of rapid advances in technology.

Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells

Stem cell therapy is an attractive approach for recovery from myocardial infarction(MI)but faces the challenges of rapid diffusion and poor survival after transplantation.Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI.Forty-five minipigs underwent left anterior descending artery(LAD)ligation and were equally divided into three groups 2 months later(collagen scaffold loading with human umbilical mesenchymal stem cell(hUMSC)group,hUMSC group,and placebo group(only phosphate-buffered saline(PBS)injection)).Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen scaffold.Echocardiography and cardiac magnetic resonance imaging(CMR)showed much higher left ventricular ejection fraction(LVEF)and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment.There were also higher densities of vWf-,α-sma-,and cTnT-positive cells in the infarct border zone in the collagen/cell group,as revealed by immunohistochemical analysis,suggesting better angiogenesis and more cardiomyocyte survival after MI.Thus,the injectable collagen scaffold was safe and effective on a large animal myocardial model,which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.

Interconnected N/P co-doped carbon nanocage as high capacitance electrode material for energy storage devices

Heteroatom doping carbon materials exhibit a huge application potential for energy storage devices(ESDs).Herein,interconnected N/P co-doped carbon nanocage(NP-CNC)was synthesized from pyrene molecules by using nano-MgO as template and melamine-phytic acid supramolecular aggregate as dopant coupled with KOH activation.The as-prepared NP-CNC possesses interconnected nanocages for electron transportation and abundant micropores for ion adsorption.Moreover,co-doped N/P species in NP-CNC provide active sites and additional pseudocapacitance.Consequently,NP-CNC as electrode material for symmetric supercapacitor exhibits a high gravimetric capacitance of 435 F·g^(-1) at 0.05 A·g^(-1),high volumetric capacitance of 274 F·cm^(-3) at 0.032 A·cm^(-3),and long cycle lifespan with 96.1%capacitance retention after 50,000 cycles.Furthermore,NP-CNC as cathode for zinc-ion hybrid supercapacitor delivers satisfactory energy and power densities of 130.6 Wh·kg^(-1)(82.3 Wh·L^(-1))and 14.4 kW·kg^(-1)(9.1 kWL^(-1)).This work paves a promising approach to the preparation of high capacitance NP-CNC for ESDs.

Cardiopulmonary resuscitation and termination of resuscitation on out-of-hospital cardiac arrest in China

To the Editor: Out-of-hospital cardiac arrest (OHCA) is a major public health challenge. Early initiation, good quality cardiopulmonary resuscitation (CPR), and the use of an automated external defibrillator (AED) have been reported to significantly improve the survival and long-term outcomes in survivors of OHCA.

What is an effective cardiopulmonary resuscitation training mode?

To the Editor:Out-of-hospital cardiac arrest(OHCA)is a serious threat to people's lives and safety.The annual incidence of OHCA in North America is approximately 55/100,000,and it is approximately 59/100,000 in Asia.[1,2]How can the success rate of resuscitation be improved in patients with cardiac arrest?The American Heart Association(AHA)and the European Resuscitation Council have put forward their own cardiopulmonary resuscitation(CPR)guidelines,which are constantly updated with the latest research evidence.CPR training is also an important part of the guidelines.[3,4]Chinese colleagues also try to improve the success rate of rescuing patients with cardiac arrest based on the experience of their international counterparts and combine it with Chinese characteristics.CPR training is in full swing,which includes the training of first responders and medical staff.