Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

AIM To study the flavonoids from the leaves of Cinnamomum camphora(L.)Presl.and their antioxidant activities.METHODS The 95％ethanol extraction from the leaves of C.camphora was isolated and purified by liquid-liquid extraction,macroporous adsorption resin chromatography,HW-40C gel column chromatography,molecular exclusion chromatography and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH method.RESULT Ten flavonoids were isolated and identified as(2R,3S)-7-methoxy-5-O-β-D-glucopyranosyl-afzelechin(1),quercetin-3-O-sambubioside(2),quercetin-3-O-β-D-apiosyl-(1→2)-β-D-glucoside(3),quercetin-3-O-robibioside(4),kaempferol-3-O-β-D-rutinoside-7-O-β-D-glucoside(5),kaempferol-3-O-α-L-rhamnoside-7-O-β-D-glucoside(6),5,3'-di-O-methyl-epicatechin(7)、cinchonain Ⅱb(8)、quercetin-3,4'-di-O-β-D-glucoside(9)、(-)-epicatechin(10).The IC50 value of compound 8 scavenging DPPH free radical was 4.8 μg/mL.CONCLUSION Compound 1 is a new compound,and compound 2-6 are obtained from Cinnamomum genus for the first time,compound 7-9 are first isolated from this plant.Compound 8 shows good antioxidant activities..

Accurate receptor/ligand binding free energy calculations can greatly accelerate drug discovery by identifying highly potent ligands. By simulating the change from one compound structure to another, the relative binding free energy (RBFE) change can be calculated based on the theoretically rigorous free energy perturbation (FEP) method. However, existing FEP-RBFE approaches may face convergence challenges due to difficulties in simulating non-physical intermediate states, which can lead to increased computational costs to obtain the converged results. To fundamentally overcome these issues and accelerate drug discovery, a new combined-structure RBFE (CS-FEP) calculation strategy was proposed, which solved the existing issues by constructing a new alchemical pathway, smoothed the alchemical transformation, increased the phase-space overlap between adjacent states, and thus significantly increased the convergence and accelerated the relative binding free energy calculations. This method was extensively tested in a practical drug discovery effort by targeting phosphodiesterase-1 (PDE1). Starting from a PDE1 inhibitor (compound 9, IC₅₀ = 16.8 μmol/L), the CS-FEP guided hit-to-lead optimizations resulted in a promising lead (11b and its mesylate salt formulation 11b-Mesylate, IC₅₀ = 7.0 nmol/L), with ∼2400-fold improved inhibitory activity. Further experimental studies revealed that the lead showed reasonable metabolic stability and significant anti-fibrotic effects in vivo.

Objective To evaluate the effects of anterior cruciate ligament (ACL) reconstruction timing on the motor performance and proprioception by clinical evaluation as well as proprioception and motor performance tests on the patients more than 2 years after ACL reconstruction. Methods The patients who underwent ACL reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from January 2015 to January 2021 and met the inclusion criteria were followed up,and the postoperative data were collected retrospectively.Fifty-six patients who met the inclusion criteria were included in this study and categorized into two groups:early surgery (n=28,who underwent ACL reconstruction ≤3 weeks after injury) and delayed surgery (n=28,who underwent ACL reconstruction >3 weeks after injury).The basic information,clinical evaluation results,proprioception,and motor performance were compared between the two groups. Results The ACL return to sport after injury scale (ACL-RSI) score in the early surgery group was higher than that in the delayed surgery group [(68.68±22.04)scores vs. (55.82±24.87)scores,P=0.045].There was no difference in the range of motion of the knee joint,the positive rate of pivot shift test,or the scores of Tegner,Marx,Lysholm,knee injury and osteoarthritis outcome score (KOOS),and international knee documentation committee (IKDC) between the two groups (all P>0.05).Although there was no significant difference in range of motion of the knee joint between the two groups,the proportion of knee flexion and extension affected in the early surgery group was smaller than that in the delayed surgery group.Neither motor performance (isokinetic strength test,Y-balance test,and single-leg jump test) nor proprioception had difference between the two groups (all P>0.05). Conclusions Early ACL reconstruction outperformed delayed ACL reconstruction in improving the psychological health,emotions,and confidence in returning to sport,accelerating functional recovery of the patients.The timing of ACL reconstruction has no significant effect on the short-term postoperative knee stability,knee function,motor performance,or proprioceptive recovery of the patients.Early ACL reconstruction is recommended for improving the clinical outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Proprioception/physiology* ; Retrospective Studies ; Male ; Female ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Postoperative Period ; Time Factors ; Return to Sport ; Recovery of Function ; Knee Joint/physiopathology* ; Young Adult

Objective To evaluate the effects of knee flexor and extensor strength on the subjective function and motor performance of knees after anterior cruciate ligament reconstruction. Methods A total of 53 patients who underwent anterior cruciate ligament reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from June 2015 to June 2021 and met the inclusion criteria were enrolled in this study.The patients were followed up time for at least 2 years.An isometric muscle strength test system was used to measure the strength of bilateral quadriceps and hamstring muscles.The patients were grouped according to whether the limb symmetry index (LSI) of peak torque of quadriceps and hamstring muscle reached 85% at an angular velocity of 60°/s.Specifically,26 patients were classified into group A (LSI≥85%) and 27 patients were classified into group B (LSI<85%).The subjective function and motor performance of knees were compared between the two groups. Results In terms of subjective function of knees,the international knee documentation committee (IKDC) score (88.76±9.93 vs. 81.08±12.57,P=0.017) and knee injury and osteoarthritis outcome score (KOOS) (86.27±8.96 vs. 80.22±11.31,P=0.036) were different between groups A and B.There was no significant difference in Lysholm score [95.0 (79.8,100.00) vs. 86.00 (66.00,100.00),P=0.238],ACL return to sports after injury scale score (66.08±22.25 vs. 61.12±23.53,P=0.434),Marx score [6.00 (4.75,7.00) vs. 6.00 (4.00,7.00),P=0.805] or Tegner activity score [8.00 (4.00,12.00) vs. 4.00 (2.00,12.00),P=0.566] between the two groups.In terms of motor performance,the single-leg triple hop LSI (0.92±0.13 vs. 0.81±0.18,P=0.016) and single-leg crossover hop LSI (0.96±0.12 vs. 0.84±0.22,P=0.021) showed significant differences between groups A and B,while there was no significant difference in single-leg hop LSI (0.90±0.18 vs. 0.79±0.25,P=0.116) between the two groups.In addition,there was no statistical significance in proprioception [30°:8.83±4.66 vs. 10.73±4.63,P=0.143;45°:6.94±3.82 vs. 7.66±3.93,P=0.504;60°:4.10 (3.20,4.72) vs. 3.90 (2.30,5.20),P=0.493] or Y-balance test results [anterior LSI:0.98 (0.84,1.02) vs. 0.94 (0.86,0.98),P=0.328;posterolateral LSI:1.00±0.08 vs. 0.97±0.07,P=0.249;posteromedial LSI:1.00 (0.97,1.03) vs. 0.96 (0.93,1.03),P=0.179] between groups A and B. Conclusion The patients with good symmetry of quadriceps and hamstring muscle strength after anterior cruciate ligament reconstruction had better subjective function and movement performance of knees than the patients with poor symmetry,which was mainly reflected in the IKDC score,KOOS,single-leg triple hop,and single-leg crossover hop.
Humans ; Anterior Cruciate Ligament Reconstruction ; Muscle Strength/physiology* ; Male ; Quadriceps Muscle/physiology* ; Female ; Adult ; Anterior Cruciate Ligament Injuries/physiopathology* ; Hamstring Muscles/physiopathology* ; Knee Joint/physiopathology* ; Anterior Cruciate Ligament/physiopathology* ; Torque ; Knee/physiopathology*

Objective To investigate the effects of rotation stability after anterior cruciate ligament reconstruction (ACLR) on subjective outcomes,sport performance,psychological readiness,and return to sport. Methods The patients who underwent ACLR in the Sports Hospital,National Institute of Sports Medicine,General Administration of Sport of China from January 2015 to January 2021 were followed up during the period from November 2022 to December 2023.The patients were grouped according to the results of the pivot shift test (PST) of the affected knee at the last follow-up visit.A total of 66 patients who participated in the follow-up and met the inclusion and exclusion criteria were finally enrolled in this study,including 32 patients showing a negative PST result (stable group) and 34 patients showing a positive PST result (unstable group).The basic information,subjective function score,and return-to-sport performance were compared between the two groups. Results In terms of sport performance,the two groups showed differences in the limb symmetry index in single-leg hops,triple hops,and crossover hops (P=0.028,P=0.024,and P=0.044,respectively).The anterior cruciate ligament-return to sport after injury scale score was higher in the stable group than in the unstable group [(70.44±22.82) scores vs. (53.44±21.74) scores,P=0.003].The mean of KT-2000 test results in the stable group was lower than that in the unstable group [(0.53±1.02) mm vs. (2.06±2.31) mm,P=0.001].The Lysholm score,international knee documentation committee score,knee injury and osteoarthritis outcome score,Tegner score,and Marx score did not have significance between the two groups (all P>0.05).The return-to-sport rate was 43.8% (including 14.3% reaching safe return criteria,which accounted for 6.3% in all the patients) in the stable group and 35.3% (including 8.3% reaching safe return criteria,which accounted for 2.9% in all the patients) in the unstable group.There was no difference in the 60°/s isokinetic muscle strength,maximal muscle strength ratio of the affected extensor-flexor muscles,or Y-balance test result between the two groups (all P>0.05). Conclusions Knee joint rotational instability after ACLR results in poor performance in single-leg hops,triple hops,and crossover hops,low psychological readiness,and anterior-posterior knee laxity.In short- to medium-term follow-up for ACLR,the return-to-sport rate remained low regardless of knee joint rotational stability,with the majority of patients failing to meet safe return criteria.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation* ; Male ; Female ; Knee Joint/surgery* ; Athletic Performance/physiology* ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Joint Instability/physiopathology* ; Return to Sport ; Rotation ; Young Adult

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 μm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.
Chromatography, High Pressure Liquid ; Paeonia ; Acetonitriles