The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Construction of a caries diagnosis model based on microbiome novelty score / 华西口腔医学杂志

OBJECTIVES@#This study aimed to analyze the bacteria in dental caries and establish an optimized dental-ca-ries diagnosis model based on 16S ribosomal RNA (rRNA) data of oral flora.@*METHODS@#We searched the public databa-ses of microbiomes including NCBI, MG-RAST, EMBL-EBI, and QIITA and collected data involved in the relevant research on human oral microbiomes worldwide. The samples in the caries dataset (1 703) were compared with healthy ones (20 540) by using the microbial search engine (MSE) to obtain the microbiome novelty score (MNS) and construct a caries diagnosis model based on this index. Nonparametric multivariate ANOVA was used to analyze and compare the impact of different host factors on the oral flora MNS, and the model was optimized by controlling related factors. Finally, the effect of the model was evaluated by receiver operating characteristic (ROC) curve analysis.@*RESULTS@#1) The oral microbiota distribution obviously differed among people with various oral-health statuses, and the species richness and species diversity index decreased. 2) ROC curve was used to evaluate the caries data set, and the area under ROC curve was AUC=0.67. 3) Among the five hosts' factors including caries status, country, age, decayed missing filled tooth (DMFT) indices, and sampling site displayed the strongest effect on MNS of samples (P=0.001). 4) The AUC of the model was 0.87, 0.74, 0.74, and 0.75 in high caries, medium caries, low caries samples in Chinese children, and mixed dental plaque samples after controlling host factors, respectively.@*CONCLUSIONS@#The model based on the analysis of 16S rRNA data of oral flora had good diagnostic efficiency.

Gonioscopy-assisted transluminal trabeculotomy for secondary high intraocular pressure after vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of gonioscopy-assisted transluminal trabeculotomy(GATT)for secondary high intraocular pressure after vitrectomy.METHODS: A retrospective study was conducted on 10 patients(15 eyes)with secondary high intraocular pressure(IOP)after vitrectomy treated with GATT in Department of Ophthalmology, Chengdu First People's Hospital from January 2019 to May 2022. The best-corrected visual acuity(BCVA), IOP, number of IOP-lowering drugs, and complications before operation and at 1d, 1wk, 1, 3 and 6mo after operation were recorded, and the surgical success rate was analyzed.RESULTS:There was no difference in BCVA before and 6mo after operation(Z=0, P=1). The mean IOP decreased from 28.33±9.48mmHg to 17.47±3.78(1d), 18.8±3.29(1wk), 19.13±3.62(1mo), 20.31±3.66(3mo)and 18.03±3.23mmHg(6mo; all P<0.05). The average medication used before surgery was 2(2, 4), and the average medication used 6mo after surgery was 1(0, 2), which was significantly decreased(P<0.001). The total success rate of surgery at 1d, 1wk, 1, 3 and 6mo after surgery was 87%(13 eyes), 93%(14 eyes), 87%(13 eyes), 73%(11 eyes)and 93%(14 eyes)respectively. The main postoperative complications were transient hyphema(10 eyes, 67%)and transient elevated IOP(5 eyes, 33%). No complications seriously affecting the vision occurred.CONCLUSION: GATT is safe and effective in the treatment of secondary high intraocular pressure after vitrectomy.

Epidemiologic characteristics and influencing factors of influenza outbreaks in Guangdong Province, 2015-2022 / 中华流行病学杂志

Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.

The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0<LGE%<5%, 5%≤LGE%<15% and LGE%≥15% groups. There were significant survival differences between these 4 groups whether for primary endpoint or secondary endpoint (all P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.

Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Gait phase recognition in intelligent above-knee prosthesis based on fuzzy logic algorithm / 中国康复理论与实践

ObjectiveAiming at the need of control strategy switching of intelligent above-knee prosthetic, taking the plantar pressure of human walking as the research object, and based on fuzzy logic algorithm, a gait phase division method based on plantar pressure of prosthetic is proposed. MethodsThree flexible force sensors installed on the soles of the false feet were used to collect the plantar pressure information of the test object under three different walking modes (walking on the flat road, walking downhill and walking down the stairs). After data fusion processing, it was sent to the fuzzy logic controller, and the recognition results were output according to the IF-THEN rule, the scale and sensitivity factor. ResultsThrough the testing of five healthy people as substitute, the results showed that the accuracy of gait phase recognition for walking on the flat road, walking down the stairs and walking downhill were (95.3±2.4)%, (81.5±6.3)% and (90.7±3.5)%, respectively. ConclusionThe accuracy of recognition basically meets the requirements in this project. This method can be applied in the gait phase recognition of intelligent above-knee prosthetic.

Surgical treatment of retrograde type A aortic dissection after thoracic endovascular aortic repair for Stanford type B aortic dissection / 中国胸心血管外科临床杂志

@#Objective     To analyze the etiologies, surgical treatment and outcomes of retrograde type A aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection. Methods     The clinical data of patients with RTAD after TEVAR for Stanford type B aortic dissection receiving operations in Changhai Hospital from March 2014 to August 2018 were analyzed. All patients were followed-up by clinic interview or telephone. Results     A total of 16 patients were enrolled, including 13 males and 3 females with a mean age of 49.1±12.2 years. The main symptoms of RTAD were chest pain in 12 patients, headache in 1 patient, conscious disturbance in 1 patient, and asymptomatic in 2 patients. All the 16 patients received total arch replacement with the frozen elephant trunk technique. Bentall procedure was used in 2 patients, aortic root plasticity in 10 patients and aortic valve replacement in 1 patient. The primary tear in 10 patients was located in the area which were anchored by bare mental stent, and in the other 6 patients it was located in the anterior part of ascending aorta. The mean cardiopulmonary bypass time was 152.2±29.4 min, aortic cross-clamping time was 93.6±27.8 min and selective cerebral perfusion time was 29.8±8.3 min. There was no death in hospital or within postoperative 30 days. The follow-up period was 32-85 (57.4±18.3) months. No death occurred during the follow-up period. One patient underwent TEVAR again 3 years after this operation and had an uneventful survival. Conclusion     Total arch replacement with the frozen elephant trunk technique is a suitable strategy for the management of RTAD after TEVAR for Stanford type B aortic dissection.

Assessment of myocardial viability in ischemic heart disease by integrated PET/MR / 中华核医学与分子影像杂志

Objective:To evaluate the value of integrated PET/MR in assessing myocardial viability in ischemic heart disease.Methods:A total of 39 patients (28 males, 11 females; age (60.1±12.0) years) diagnosed with ischemic heart disease in Xuanwu Hospital, Capital Medical University were retrospectively enrolled from September 2020 to December 2021. All patients underwent cardiac 13N-NH 3·H 2O and 18F-FDG PET/MR examinations. Late gadolinium enhancement (LGE) sequence was included in MRI scan. PET and MRI images were analyzed and myocardial viability of each myocardial segment was evaluated according to the American Heart Association (AHA) 17 segment method. The extent of left ventricular infarcted myocardium was measured based on PET and MRI images. Weighted Kappa test was used to evaluate the agreement of PET and MRI in assessing myocardial viability. The extent of infarcted myocardium measured by PET and MRI was compared by paired- t test, and Pearson correlation analysis was used to assess the correlation between them. Results:There was a moderate agreement between PET and MRI in assessing myocardial viability ( Kappa=0.532, P<0.001), with the agreement rate of 69.83%(463/663). There was no significant difference but strong correlation between the extents of infarcted myocardium measured by PET and MRI ((23.89±14.23)% vs (23.55±11.90)%; t=-0.24, P=0.809; r=0.79, P<0.001). In segments with normal perfusion and metabolism on PET, 22.52% (100/444) showed abnormal enhancement on MRI. On the other hand, 39.89% (73/183) of the segments classified as non-viable on MRI showed normal or viable on PET. Conclusion:Integrated PET/MR is able to take full advantage of the complementary nature of PET and MRI, achieving the comprehensive and accurate evaluation of myocardial viability.

Interpretation of presynaptic dopaminergic PET imaging results / 中华核医学与分子影像杂志

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Correlation analysis for the lateral condylar tibial plateau fracture and complete medial collateral ligament rupture / 中华骨科杂志

Objective:To investigate the relationship between the CT images of a lateral condylar tibial plateau fractures and complete medial collateral ligament (MCL) injury.Methods:Data of 59 patients with lateral condylar fracture of tibial plateau complicated with MCL injury admitted to Tianjin Hospital from January 2020 to November 2021 were collected, including 32 males and 27 females, aged 42.4±12.3 years (range, 19-65 years), there were 26 cases of extension injury and 33 cases of flexion injury. The patients were separated into two groups: those with partial MCL injury and those with total rupture based on preoperative MR examination and intraoperative valgus stress test following fracture fixation. According to the ABC fracture classification of lateral condyle tibial plateau proposed by Sun et al., the fracture locations were determined on CT images, and the lateral plateau collapse depth (LPD) was measured. The relationship between LPD and MCL complete rupture was analyzed by receiver operating characteristic (ROC) curve.Results:Among 59 patients with lateral condylar tibial plateau fracture and MCL injury, 42 had partial injuries and 17 had complete ruptures. According to the ABC fracture classification, there were 26 cases of extension injury (involving area A), 21 cases of AB type, and 5 cases of ABC type; and 33 cases of flexion type injury, 19 cases of B type, 12 cases of BC type, and 2 cases of C type. All the 17 cases of MCL complete fracture occurred in extension injury, including type AB (14 cases) and type ABC (3 cases). The difference between the mean LPDs of the MCL full rupture group and the partial injury group was not statistically significant ( t=0.11, P=0.567), and the mean LPDs of both groups were 11.7±5.3 mm (range, 4.3-28.1 mm) and 11.5±4.8 mm (range, 3.8-23.6 mm), respectively. The area under the curve (AUC) of the ROC curve analysis was 0.504, and there was no statistical correlation between lateral platform collapse depth and MCL injury. Among the 26 patients with extensional injury area, MCL was completely ruptures in 17 cases and partially injury in 9 cases, LPD was 11.7±5.3 mm (range, 4.3-28.1 mm) and 6.6±1.8 mm (range, 3.8-9.4 mm), respectively, and the difference was statistically significant ( t=3.57, P=0.009). The best predictive cut-off value of LPD was 7.25 mm, the sensitivity was 88.2%, the specificity was 77.8%, and the AUC was 0.868. Conclusion:When the lateral condyle fracture of the tibial plateau is located in the extensional injury area (involving the A area in the ABC fracture classification) and the LPD measured on the CT image is greater than 7.25 mm, the complete rupture of the MCL should be considered. Clinical MCL repair is required after the fracture fixation surgery for improved surgical outcomes.

The application of silent MR angiography in the imaging of brain arteriovenous malformation in children / 中华放射学杂志

Objective:To explore the application value of silent MR angiography (MRA) in imaging of brain arteriovenous malformation (BAVM) in children.Methods:A total of 20 children with BAVM confirmed by digital subtraction angiography (DSA) were retrospectively collected. All children were imaged by silent MRA and time-of-flight MRA (TOF MRA) in the same examination. The image quality of feeding artery, nidus and drainage vein of BAVM was evaluated using the four-point method. Wilcoxon rank-sum test was utilized to compare the image quality scores between silent MRA and TOF MRA. Weighted Kappa statistics used to evaluate the inter-modality agreement of silent MRA and TOF MRA with DSA in displaying of angioarchitecture characteristics and determination of Spetzler-Martin grading.Results:Among the 20 BAVMs, significant differences in image quality scores of the nidus (2.75±0.55 versus 2.20±0.70) and drainage vein (2.60±0.68 versus 2.20±0.77) were observed between silent MRA and TOF MRA ( Z=-3.05, P=0.002; Z=-2.13, P=0.033, respectively). The agreement between silent MRA and DSA was excellent in nidus size grading, deep venous drainage, associated aneurysm and SM grading (Kappa 0.91, 1.00, 0.83 and 0.93, respectively); The agreement between TOF MRA and DSA was fair to moderate (Kappa 0.46, 0.59, 0.35 and 0.47, respectively). Conclusions:Silent MRA showes better image quality compared to TOF MRA and improves the evaluation of angioarchitecture characteristics and Spetzler-Martin grading of BAVMs in children.

Clinical observation of post-chronic pancreatitis diabetes mellitus patients and type 2 diabetes mellitus patients / 中华胰腺病杂志

Objective:To observe and compare the clinical characteristics between post-chronic pancreatitis diabetes mellitus(PPDM-C)patients and type 2 diabetes mellitus(T2DM).Methods:Data of 142 cases of CP patients confirmed in Shanghai Pudong New Area Gongli Hospital from January 2018 to December 2021 were collected, all the patients were divided into CP group without diabetes mellitus ( n=60) and PPDM-C group with diabetes mellitus ( n=82) based on whether with or without diabetes mellitus. And 82 cases T2DM without CP (T2DM group, n=82) hospitalized simultaneously were collected as control group. The age, sex, body mass index, onset characteristics, laboratory examination indicators at admission (fasting blood glucose, glycosylated hemoglobin, blood creatinine, and alanine transaminase), imaging characteristics of the pancreas (pancreatic atrophy, multiple calcifications of the pancreas, pancreatic duct stones, pancreatic duct dilation, and pancreatic duct obstruction), and treatments and efficacy of diabetes were recorded. Results:Compared with T2DM group, PPDM-C group had lower body mass index (22.2 kg/m 2vs 24.6 kg/m 2), and glycosylated hemoglobin levels (7.34% vs 9.20%) (all P values <0.001), higher alanine transaminase levels (33.00 U/L vs 18.65 U/L, P =0.021). And they had more upper abdominal pain, nausea, vomiting, weight loss and diarrhea symptoms. In addition, they had less use of combination of insulin and hypoglycemic drugs to control blood glucose. And compared with CP group, PPDM-C group had higher body mass index (22.06 kg/m 2vs 21.18 kg/m 2), higher glycosylated hemoglobin levels (7.34% vs 5.70%), higher fasting blood-glucose levels (7.91 mmol/l vs 5.31 mmol/l), higher alanine transaminase levels (33.00 U/L vs 26.50U/L), and their differences were statistically significant (all P values <0.05). And they had higher incidence of pancreatic atrophy, multiple calcifications in the pancreatic duct and pancreatic duct obstruction (all P values <0.05). Conclusions:PPDM-C patients are more likely to experience digestive system symptoms such as abdominal pain than T2DM patients, while their pancreatic malfunction is more likely to occur compared to CP patients. More attentions to PPDM-C associated clinical manifestations, biochemical and imaging changes could identify patients at potential risk for early diagnosis and treatment earlier.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis / 老年心脏病学杂志（英文版）

BACKGROUND@#Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy.@*METHODS@#We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses.@*RESULTS@#Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant.@*CONCLUSIONS@#The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Activation of PXR causes drug interactions with Paxlovid in transgenic mice

Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster. Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid. By using recombinant human cytochrome P450s (CYPs), we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism. The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice, which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV. Pregnane X receptor (PXR) is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression. We next explored the impact of drug- and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5. We found that PXR activation increased CYP3A4/5 expression, accelerated NMV metabolism, and reduced the systemic exposure of NMV. In summary, our work demonstrated that PXR activation can cause drug interactions with Paxlovid, suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.

Reproducible Abnormalities and Diagnostic Generalizability of White Matter in Alzheimer's Disease / 神经科学通报·英文版

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.

Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database

Purpose@#We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. @*Results@#2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. @*Conclusion@#EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

Puncture and Needle Picking Action of Venipuncture Manipulator / 医用生物力学

Objective To propose a new multi-joint series venipuncture system, explore the mechanics and kinematics-based related control problems involved in needle insertion and needle picking during the puncture process, and verify feasibility of this system. Methods A puncture manipulator was built, and needle displacement control algorithm was proposed by combing with the puncture mechanics model. The the forward kinematics was calculated by using DH method, so as to obtain the tip coordinates. Then the inverse kinematics was calculated by using the geometric method. The forward and inverse processes were closely connected. The position error of the end coordinates before and after needle picking was compared by using the method of kinematics positive solution-inverse solution-re-positive solution. Finally, experimental verification and simulation were conducted by combining with the physical object. Results Through simulation and experiments, accuracy of the theoretical model was verified. The needle insertion algorithm could be used to achieve success with only one needle insertion, which provided theoretical basis for the control of robot arm. The position error before and after needle picking could be controlled within 1 mm from the end trajectory. The end needle tip of robot arm was almost kept fixed during the needle picking process. Therefore, this needle picking scheme was feasible and could basically verify that the needle picking action of robot arm met the accuracy and safety requirements. Conclusions The venipuncture manipulator truly simulates the needle insertion and needle picking action during the puncture process, and can safely and accurately realize the needle insertion and needle picking action with needle tip as the fixed point, indicating that it has certain clinical value.

The Action Effect of Two Kinds of Lumbar Massage Obliquity Manipulation with Different Lumbar Degeneration Degrees: A Comparative Study / 医用生物力学

Objective To compare the action effect of traditional and modified lumbar massage obliquity manipulation with different degrees of lumbar degeneration. Methods The biomechanical model of quality-spring-damping system lumbar spine was established and massage forces from professional massage doctors were collected. The force was used as input of the model, and lumbar degeneration was simulated by increasing elastic coefficient of the spring and damping coefficient of the damping in the model. By using MATLAB/ Simulink simulation technology, the effects of massage obliquity manipulation ( the maximum relative displacement and maximum acceleration) with different degrees of lumbar degeneration were obtained for comparative analysis.Results When the lumbar spine was degenerative, the maximum relative displacement and maximum acceleration of each segment were obtained under two manipulations. With the increase of lumbar degenerationdegree, the maximum relative displacement and maximum acceleration of each segment under two manipulations showed a downward trend, and the attenuation rate of the maximum relative displacement and maximum acceleration of each segment under two manipulations was obtained. Conclusions When degenerative changes in the spine do not occur, the effectiveness of traditional lumbar massage obliquity manipulation is slightly better than that of modified lumbar massage obliquity manipulation, but the safety of modified lumbar massage obliquity manipulation is obviously better than that of the traditional lumbar massage obliquity manipulation, so the modified lumbar massage obliquity manipulation should be used. With the aggravation of lumbar degeneration, the action effects of two manipulations are attenuated in a power function. The attenuation rate of effectiveness of modified lumbar massage obliquity manipulation is significantly faster than that of traditional lumbar massage obliquity manipulation, indicating that the modified lumbar massage obliquity manipulation should not be used in the caseof lumbar degeneration.