BACKGROUND:As the end bearing joint of the human body,the ankle joint bears the top-down pressure of the body,which leads to the ankle joint is easy to be damaged in the movement,can induce functional ankle instability,which negatively affects daily life.The study of lower extremity biomechanics in patients with functional ankle instability during counter movement jump is of great significance for scientific training,prevention of ankle injury,and clinical rehabilitation after injury. OBJECTIVE:To investigate the kinetics and kinematics of lower limbs in the longitudinal jumping of functional ankle instability population. METHODS:From March to September 2023,15 male patients with functional ankle instability and 15 healthy people,aged 22-28 years old,were recruited in Soochow University.All subjects completed counter movement jump experiment.Vicon infrared high-speed motion capture system and Kistler three-dimensional force measuring table were used to simultaneously collect the lower limb kinematics and kinetics indexes of the two groups of subjects at the take-off stage of counter movement jump,the instant off the ground,the initial landing moment and the peak moment of vertical ground reaction force. RESULTS AND CONCLUSION:(1)At the instant off the ground,the affected side of the functional ankle instability group showed smaller knee internal rotation moment(P=0.020)and smaller ankle internal rotation moment(P=0.009)compared with the affected side of the healthy control group.(2)At the moment of landing,the affected side of the functional ankle instability group showed a smaller hip flexion angle than the affected side of the healthy control group(P=0.039).Compared with the healthy control group,functional ankle instability group showed smaller hip abduction angle(P=0.022),smaller knee varus angle(P=0.010),larger knee external rotation angle(P=0.021),smaller ankle varus angle(P=0.004),and smaller external ankle rotation angle(P=0.008).(3)At the peak of vertical ground reaction force,functional ankle instability group showed a smaller ankle varus angle than healthy control group(P=0.044).(4)The results showed that the lower limb biomechanical characteristics of the patients with functional ankle instability were abnormal compared with the healthy people during counter movement jump,which mainly showed the changes of the kinematics and kinetics indexes of the lower limb joints in the sagittal plane and the frontal plane at the moment of lift-off and landing.These changes reflect that people with functional ankle instability adopt rigid take-off and landing patterns when performing counter movement jump,tend to transfer the load of the affected ankle joint to other joints of the lower limb,and show compensatory phenomenon of the healthy lower limb.Therefore,detection and correction of abnormal biomechanical features should be a part of rehabilitation training for those with functional ankle instability.

Objective To investigate the distribution characteristics of Klebsiella pneumoniae(KP),hyperviru-lent Klebsiella pneumoniae(hvKP),carbapenem-resistant Klebsiella pneumoniae(CRKP),and hypervirulent car-bapenem-resistant Klebsiella pneumoniae(hv-CRKP/CR-hvKP)in the environment of general intensive care unit(ICU)at medical institutions,and provide reference for environment assessment as well as healthcare-associated in-fection(HAI)prevention and control in ICU.Methods A total of 3 336 environmental specimens were collected from general ICUs of medical institutions in Shanghai in 2019 and 2023.After strain isolation,antimicrobial suscep-tibility testing and whole genome sequencing were conducted.Results The detection rate of KP was 1.59％(n=53),among which hvKP,CRKP,and hv-CRKP/CR-hvKP accounted for 37.74％(20/53),52.83％(28/53),and 24.53％(13/53)of the total detected strains,respectively.The main types of hvKP were ST11-KL64 and ST11-KL25,CRKP were ST15-KL19 and ST11-KL25,hv-CRKP/CR-hvKP were ST11-KL25 and ST11-KL64.The main carried resistance genes included fosA,oqx AB,tet(A),blaTEM-1B,blaKPC-2,qnrS11,etc.All strains carried viru-lence genes fimH,iutA,ent A,entB,entC,entD,entE,and entF,with only one strain carrying rmp A gene.Conclusion KP contamination is widespread in general ICU environment of medical institutions,predominantly ST11 and ST15,presenting a polymorphic distribution.CRKP and hvKP account for a relatively high proportion,and multidrug resistance is serious.Co-evolution of drug resistance and virulence presents in KP,and poses signifi-cant infection and pathogenic risks to patients,necessitating enhanced clinical vigilance and preparedness for poten-tial outbreaks.

Objective To investigate the distribution characteristics of Klebsiella pneumoniae(KP),hyperviru-lent Klebsiella pneumoniae(hvKP),carbapenem-resistant Klebsiella pneumoniae(CRKP),and hypervirulent car-bapenem-resistant Klebsiella pneumoniae(hv-CRKP/CR-hvKP)in the environment of general intensive care unit(ICU)at medical institutions,and provide reference for environment assessment as well as healthcare-associated in-fection(HAI)prevention and control in ICU.Methods A total of 3 336 environmental specimens were collected from general ICUs of medical institutions in Shanghai in 2019 and 2023.After strain isolation,antimicrobial suscep-tibility testing and whole genome sequencing were conducted.Results The detection rate of KP was 1.59％(n=53),among which hvKP,CRKP,and hv-CRKP/CR-hvKP accounted for 37.74％(20/53),52.83％(28/53),and 24.53％(13/53)of the total detected strains,respectively.The main types of hvKP were ST11-KL64 and ST11-KL25,CRKP were ST15-KL19 and ST11-KL25,hv-CRKP/CR-hvKP were ST11-KL25 and ST11-KL64.The main carried resistance genes included fosA,oqx AB,tet(A),blaTEM-1B,blaKPC-2,qnrS11,etc.All strains carried viru-lence genes fimH,iutA,ent A,entB,entC,entD,entE,and entF,with only one strain carrying rmp A gene.Conclusion KP contamination is widespread in general ICU environment of medical institutions,predominantly ST11 and ST15,presenting a polymorphic distribution.CRKP and hvKP account for a relatively high proportion,and multidrug resistance is serious.Co-evolution of drug resistance and virulence presents in KP,and poses signifi-cant infection and pathogenic risks to patients,necessitating enhanced clinical vigilance and preparedness for poten-tial outbreaks.

Objective: To develop a simple digital chylous plasma device and validate its ability to accurately, standardly, and non-destructively determine chylous plasma in blood banks and clinical transfusions in hospitals. Methods: A digital chylous plasma assessment device was designed and manufactured. This device was used to measure the chylous degrees of chylous plasma samples before freezing, after freeze-thawing, before viral inactivation, and after viral inactivation. The measured chylosity index values were categorized according to the requirements specified in Appendix A of the Chinese national standard GB 18469-2001 "Quality Requirements for Whole Blood and Blood Components". This process established a digital standard for chylous plasma, enabling the identification of severe, moderate and mild chylous plasma, and non-chylous plasma. Results: The initial simple product of the digital chylous assessment device was successfully designed and manufactured. There was no significant difference in the degree of chylous plasma between pre-freezing 468.11±217.73 lux and post-thawing 538.91±273.39 lux of chylous plasma (P>0.05), or between pre-viral inactivation 858.33±387.79 lux and post-viral inactivation 928.33±166.51 lux of chylous plasma (P>0.05). The median of chylous degree values for plasma chylous index grades 0 to 6 were 45 lux, 250 lux, 620 lux, 835 lux, 1 130 lux, 1 390 lux, and 1 700 lux, respectively. The defined cutoff values/ranges for the chylous degree values corresponding to plasma chylous index grade 0 to 6 were ≤125 lux, 126-465 lux, 466-740 lux, 741-1 000 lux, 1 001-1 233 lux, 1 234-1 560 lux, and ≥1 561 lux. Conclusion: This study successfully developed the initial product of the digital chylous device and established digital standards for classifying chylous plasma. The device demonstrates the potential to meet the needs for assessment of chylous plasma in both blood banks and clinical transfusions in hospitals, thereby promoting the development and application of standardized, non-destructive chylous plasma assessment technology.

ObjectiveTo explore the possible mechanism of Danggui Sini Granules （当归四逆颗粒） in treatment of coronary heart disease with cold congealing and blood stasis syndrome. MethodsFifty SD rats were randomly divided into a blank group， a model group， a Danshen Pill （丹参滴丸） group， and a low- and high-dosage Danggui Sini Granules group， with 10 rats in each group. Except for the blank group， the rat model of coronary heart disease with cold congealing and blood stasis syndrome was established by repeated cold stimulation at low temperature combined with intraperitoneal injection of posterior pituitary hormone in all other groups. In the 6th week of modelling， 0.073 g·kg^-1·d^-1 of compound Danshen Pill was given to the Danshen Pill group， 20.2 and 40.4 g·kg^-1·d^-1 of Danggui Sini Granules were given to the low- and high-dose Danggui Sini Granules groups， respectively， and 0.2 ml/10 g of sterile water was given to the blank group and the model group， all for 2 consecutive weeks. The general conditions of the rats were recorded， and the body mass was compared weekly. At the end of the intervention， electrocardiogram， blood rheological indexes， including whole blood low-cut viscosity， whole blood high-cut viscosity， erythrocyte aggregation index， and cardiac index were detected to evaluate the effect of the medication， and HE staining was used to observe the myocardial histopathological changes， TUNEL staining to detect the apoptotic situation of cardiomyocytes， and ELISA to detect the serum thyroid-stimulating hormone （TSH）， free triiodothyronine （FT₃）， free tetraiodothyronine （FT₄） levels and thromboxane B₂ （TXB₂）， 6-keto-prostaglandin F1α （6-Keto-PGF_1α）， endothelin 1 （ET-1）， and nitric oxide （NO） levels. ResultsCompared with the blank group at the same time point， the body mass of rats in the remaining groups decreased at all time points （P＜0.05 or P＜0.01）； compared with the model group at the same time point， the body mass of rats in high-dose Danggui Sini Granules group and Danshen Pill group increased at the 6th and 7th weeks （P＜0.05 or P＜0.01）. In the blank group， the S-T segment of the electrocardiogram was close to the isoelectric line， the myocardial structure was regular， the fibres were closely arranged， and the nuclei of the cells were intact and neatly aligned； in the model group， the S-T segment of the electrocardiogram significantly elevated， and the arrangement of the myocardial fibres was obviously disordered， with myocardial cells appearing to be swollen， necrotic， and infiltrated by inflammatory cells， and the apoptosis-positive cells of the cardiac muscle cells obviously increased； in each of the medication groups， the electrocardiogram had a lowered S-T segment， and myocardial fibres were aligned， myocyte structure and morphology were improved， inflammatory cells reduced， and the number of apoptosis-positive cells significantly reduced. Compared with the blank group， the cardiac index， whole blood high cut viscosity， whole blood low cut viscosity， erythrocyte aggregation index increased in the model group， and the serum levels of TSH， FT₃， FT₄， NO， 6-Keto-PGF_1α significantly reduced， and the levels of ET-1 and TXB₂ significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， the levels of cardiac index， whole blood high cut viscosity， whole blood low cut viscosity， erythrocyte aggregation index， ET-1 and TXB₂ significantly decreased and the levels of NO and 6-Keto-PGF_1α significantly increased in each medication group， and the serum levels of TSH， FT₃， and FT₄ elevated in the high-dose Danggui Sini Granules group and Danshen Pill group （P＜0.05 or P＜0.01）. The serum TSH level of rats in the low-dose Danggui Sini Granules group was lower than that in Danshen Pill group and the high-dose Danggui Sini Granules group （P＜0.01）. ConclusionDanggui Sini Granules have the effect of alleviating myocardial injury in coronary heart disease with cold congealing and blood stasis syndrome， and its mechanism may be related to reducing myocardial cell apoptosis， improving energy metabolism， and regulating the level of vasoactive factors.

Objective This study investigated lower limb biomechanics and lateral asymmetry during the continuous vertical jump(CVJ)landing process in individuals with unilateral functional ankle instability(FAI)and compared these characteristics with those of healthy individuals.Methods Fourteen males with unilateral FAI were selected as the experimental group,and 14 males without ankle joint injury were matched to the control group.Both the groups performed 30 CVJ landing tasks.Lower limb kinematic and kinetic characteristics during the 1st,15th,and 30th CVJ landings were synchronously collected using Vicon and Kistler equipment,and a 2×3 mixed analysis of variance was adopted for the data.Results In the execution of CVJ landing tasks,patients with FAI demonstrated no significant differences in the kinematic and kinetic characteristics of the affected limbs compared with healthy controls.However,a greater degree of lateral asymmetry was observed in the FAI group,particularly in the symmetry index(SI)of the vGRF peak.Despite the increase in the number of jump landings and consequent increase in fatigue levels,which led to adjustments in lower limb movement patterns,these adjustments did not appear to have a significant impact on the biomechanical characteristics and asymmetry of the affected limb in patients with FAI.Conclusions This study provides a theoretical basis for the prevention of recurrent ankle sprains in patients with FAI,as well as rehabilitation training prior to their return to sports.These findings underscore the importance of addressing lower limb asymmetry in the rehabilitation training of patients with FAI to reduce the risk of potential long-term injuries.When formulating rehabilitation plans for patients with FAI,particular attention should be paid to the correction of lower limb asymmetry with consideration of biomechanical adaptability under different states to achieve a more comprehensive rehabilitation outcome.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

Objective:To comparatively analyze the diagnostic value of patent foramen ovale and the degree of right-to-left shunt among the traditional Valsalva maneuver (VM), the modified Valsalva maneuver (mVM) and the compression of the inferior vena cava combined with modified Valsalva maneuver (CM).Methods:A total of 132 patients with migraine, dizziness, chest pain and other symptoms in Longgang District People′s Hospital of Shenzhen from January 2021 to December 2021 were prospectively enrolled. The detection rate of patent foramen ovale and the degree of right-to-left shunt were assessed among the rest state and after performing the auxiliary maneuvers including VM, mVM and CM respectively.Results:After performing the auxiliary maneuvers, the detection rate of patent foramen ovale was significantly increased (88.6% vs 59.8%) with statistical significance (χ 2=36.026, P<0.001). There was a significant difference in the degree of right-to-left shunt among the three auxiliary maneuvers (χ 2=25.581, P<0.001). CM was the most effective for the detection of the large right-to-left shunt, and the difference was statistically significant compared with VM and mVM ( P<0.001, P=0.002). Conclusions:Auxiliary maneuvers is crucial for the diagnosis of patent foramen ovale. Compared with VM and mVM, performing CM can further improve the detection rate of patent foramen ovale and increase the degree of right-to-left shunt.

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