Exploration of antidepressant effect and mechanism of icariside Ⅱ based on GABAergic nervous system / 中国药房

OBJECTIVE To explore the antidepressant effect and potential mechanism of icariside Ⅱ （ICSⅡ） based on the GABAergic nervous system. METHODS The male Kunming mice were randomly divided into a control group （group C， 10 mice） and a modeling group （50 mice）. The depression model was induced by chronic unpredictable mild stress （CUMS） method in the modeling group. After 21 days of stimulation， the rats of modeling group were randomly divided into depression model group （NS group）， positive control group [ECS group， oxalate escitalopram 15 mg/（kg·d）] and ICSⅡ low-dose， medium-dose and high-dose groups [ICSⅡ-L group， ICSⅡ-M group， ICSⅡ-H group； ICSⅡ 10， 20， 30 mg/（kg·d）]， with 10 mice in each group. Administration groups were given relevant medicine intragastrically， once a day， for 14 consecutive days. The sugar water preference rate， total exercise distance， immobility time in tail suspension and forced swimming experiments were detected in each group. The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed； the contents of γ-aminobutyric acid （GABA） and glutamic acid （Glu）， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins （GABA A receptor α1， GABA B receptor 1， vesicular GABA transporter， glutamate decarboxylase 67， GABA membranal transporter 3） were detected in hippocampus. RESULTS Compared with group C， the sugar water preference rate and the total exercise distance significantly reduced in NS group， while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged （P＜0.05）. The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced， with a significant decrease in the number of structurally intact neurons （P＜0.05）； the content of Glu was significantly increased， while the content of GABA， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins were significantly decreased （P＜0.05）. Compared with NS group， depression behavior in each administration group was improved， and the above indexes were mostly reversed （P＜0.05）. CONCLUSIONS ICSⅡ can improve depression behavior of depression model mice. The mechanisms may be associated with regulating the balance of GABA and Glu， increasing the synthesis， transport and release of GABA， and regulating the expressions of GABA-related receptors， so as to improve GABAergic nervous system.

Establishment of pharmaceutical care model for lower extremity artery disease based on patients’disease self-management ability / 中国药房

OBJECTIVE To construct the integrated pharmaceutical care model of in-hospital pharmaceutical care+out-hospital pharmacy outpatient service for patients with lower extremity artery disease （LEAD）， so as to improve patients’ disease self- management ability， and the efficacy and safety of therapy. METHODS The in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model was constructed for LEAD patients， including pharmaceutical evaluation， self-management ability education， and pharmacy follow-up， to perform long-term management of patients. Totally 65 LEAD patients admitted to the vascular surgery department of our hospital， receiving pharmacist management， from September， 2021 to December， 2022 were selected as the study objects， and pharmacists conducted in-hospital pharmaceutical care+continuous out-patient management. The efficacy indicators， safety indicators， and patients’s disease self-management ability indicators were compared before and after 3 months of pharmacist management. RESULTS After 3 months of pharmacists’ participation in the management of 65 patients， Fontaine stage decreased in 55 patients， there was the significant difference in Fontaine stage before and after management （P＜ 0.001）. The proportion of patients who completely followed the guidelines for medication increased from 63.1% to 96.9%； the incidence of small bleeding was reduced by 7.7% after pharmacists’ management. The scores of Morisky medication compliance and patients’ disease self-management ability were higher than 3 months ago （P＜0.001）. Patient proportion with “good” medical satisfaction increased by 18.4%. CONCLUSIONS The in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model of LEAD patients can effectively improve patients’ disease self-management ability， and improve the efficacy and safety of therapy.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Pathogenic characterization of Klebsiella pneumoniae resistant to carbapenems and polymyxin / 中华预防医学杂志

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.

Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Application of the Chinese Expert Consensus on Diabetes Classification in clinical practice / 中华内科杂志

Objective:To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification.Methods:Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC).Results:A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m 2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95% CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions:There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

Effect of age factors on pharmacodynamics of intranasal dexmedetomidine for sedation in pediatric patients undergoing transthoracic echocardiography / 中华麻醉学杂志

Objective:To evaluate the effect of age factors on the pharmacodynamics of intranasal dexmedetomidine for sedation in the pediatric patients undergoing transthoracic echocardiography(TTE).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients, aged 1-24 months, undergoing TTE from August 2019 to May 2022, were selected. This trial was performed in two parts. Part Ⅰ Pediatric patients were divided into 4 age groups: 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The initial dose of dexmedetomidine was 2.0 μg/kg in 0.1 μg/kg increment/decrement. The dose of dexmedetomidine was determined by using modified Dixon′s up-and-down method. The ED 50 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated by the Dexon-Massey method. Part Ⅱ One hundred patients were divided into 4 age groups ( n= 25 each): 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The 4 groups were further divided into 5 subgroups ( n=5 each) according to the dose of dexmedetomidine: 2.1 μg/kg subgroup, 2.2 μg/kg subgroup, 2.3 μg/kg subgroup, 2.4 μg/kg subgroup, and 2.5 μg/kg subgroup. Part Ⅰ and part Ⅱ trials were combined, and the ED 95 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated using the probit method. Results:A total of 220 pediatric patients were enrolled. There was no significant difference in ED 50 and ED 95 of dexmedetomidine intranasally administered for sedation among groups ( P>0.05). Conclusions:The pharmacodynamics of intranasal dexmedetomidine for sedation shows no significant difference in age in the pediatric patients aged 1-24 months undergoing TTE.

Effectiveness of TiRobot-assisted and free-hand percutaneous kyphoplasty via pedicle of vertebra in treatment of osteoporotic vertebral compression fracture of thoracic vertebra / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness of TiRobot-assisted and C-arm X-ray fluoroscopy assisted percutaneous kyphoplasty (PKP) via pedicle of vertebra in the treatment of osteoporotic vertebral compression fracture (OVCF) of thoracic vertebrae.@*METHODS@#The clinical data of 85 patients with OVCF of thoracic vertebrae who were admitted between January 2020 and March 2023 and met the selection criteria was retrospectively analyzed including 40 patients (50 vertebrae) undergoing PKP assisted by TiRobot (group A) and 45 patients (50 vertebrae) undergoing PKP assisted by C-arm X-ray fluoroscopy (group B). There was no significant difference in the comparison of baseline data such as gender, age, body mass index, bone mineral density T-value, fracture segment, trauma history, and preoperative numerical rating scale (NRS) score, Oswestry disability index (ODI), and Cobb angle of injured vertebra between the two groups ( P>0.05). The effectiveness evaluation indexes of the two groups, including the operation time, the volume of injected cement, the times of fluoroscopies, the length of hospital stay, and the occurrence of postoperative complications were collected and compared. Anteroposterior and lateral X-ray films and CT of the injured vertebra were reviewed at 1 day after operation to observe whether there was cement leakage and to evaluate the distribution of cement in the injured vertebra. Before and after operation, pain was assessed using the NRS score, dysfunction was assessed using the ODI, and vertebral height recovery was assessed by measuring the Cobb angle of the injured vertebrae by X-ray films.@*RESULTS@#Both groups of patients successfully completed the operation, the operation time, the volume of injected cement, the times of fluoroscopies, and the length of hospital stay in group A were significantly less than those in group B ( P<0.05). The patients in two groups were followed up 4-12 months (mean, 9.6 months). Bone cement leakage occurred in 5 vertebrae in group A and 15 vertebrae in group B after operation, all of which leaked to the intervertebral space and around the vertebral body, and the patients had no obvious clinical symptoms. The difference of bone cement leakage between the two groups was significant ( P<0.05). No severe complication such as intraspinal leakage, infection, or vascular embolism was found in the two groups. At 1 day after operation, the distribution index of bone cement in group A was mostly grade Ⅴ, which was well dispersed; while in group B, it was mostly grade Ⅱ and grade Ⅴ; the difference of bone cement distribution index between the two groups was significant ( P<0.05). The NRS score, ODI, and Cobb angle of injured vertebra in both groups were significantly improved at 1 day after operation when compared with preoperative ones ( P<0.05). There was no significant difference in the difference of the above indexes between the two groups before and after operation ( P>0.05).@*CONCLUSION@#TiRobot-assisted unilateral PKP in the treatment of OVCF of thoracic vertebrae is safe and effective, which can reduce the X-ray transmission times during operation, shorten the operation time, reduce the volume of bone cement injection, and thus decrease incidence of bone cement leakage.

Joint effects of meteorological factors and PM2.5 on age-related macular degeneration: a national cross-sectional study in China

BACKGROUND@#Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM2.5) on AMD.@*METHODS@#Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM2.5 on AMD.@*RESULTS@#The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM2.5 level during the study period was 63.1 ± 15.3 µg/m3. A significant positive association was detected between AMD and PM2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM2.5 and atmospheric pressure.@*CONCLUSIONS@#This study is among the first to characterize the coordinated effects of meteorological factors and PM2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.

Traditional Chinese Medicine in Prevention and Treatment of Renal Fibrosis in Diabetic Nephropathy by Targeting Notch Signaling Pathway： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is one of the common chronic kidney diseases （CKD） worldwide and a major cause of end-stage renal disease （ESRD）， seriously threatening and affecting the life and health of the global population. Currently， the pathogenesis of DN is considered to be closely related to factors such as glucose metabolism disorders， abnormal lipid metabolism， oxidative stress， activation of inflammatory factors， autophagy， and cell apoptosis in the continuous high-glucose environment of the body. Renal fibrosis is an important pathological feature and ultimate pathological outcome of DN. Timely intervention in renal fibrosis is of significant clinical and practical importance for the prevention and treatment of DN. Due to the limitations of western medicine in treating DN， traditional Chinese medicine （TCM） intervention in the process of renal fibrosis in DN has been widely used as a routine and potential treatment method due to its multi-component， multi-effect， and multi-target effects， effectively delaying the progression of the disease. It has been found that the Notch signaling pathway plays an important role in the development and maintenance of homeostasis in the body， and abnormal activation of the Notch signaling pathway is associated with DN. Activation of this signaling pathway plays a key role in the process of renal fibrosis. This article reviewed the regulatory mechanism of the Notch signaling pathway in renal fibrosis in DN， focusing on the relationship between targeting Notch signaling pathway by Chinese medicinal monomers and prescriptions and renal fibrosis in DN in order to provide a theoretical basis for the development of new drugs， basic research， and clinical application of TCM in the prevention and treatment of DN.

Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway / 神经科学通报·英文版

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.

Effects of occupational therapy on upper extremity for patients with stroke: a systematic review using WHO-FICs / 中国康复理论与实践

ObjectiveTo construct a framework of PICO for occupational therapy to improve upper extremity function in stroke patients based on World Health Organization Family of International Classifications (WHO-FICs), and to analyze the functional outcome of major occupational therapies to improve upper extremity in stroke. MethodsUsing the WHO-FICs framework, the databases such as Web of Science, PubMed, CNKI and SinoMed were searched for literature related to occupational therapy interventions for upper extremity function in stroke patients from the date of establishment to October, 2022, and the contents of the literature were extracted for a systematic review. ResultsTen randomized controlled trials from six countries were finally included, involving 382 participants (≥ 18 years old). The literatures were mainly from the fields of rehabilitation medicine, physics and rehabilitation medicine, neuroscience, bioengineering medicine, occupational therapy and other research fields, and were published mainly after 2013. The quality of the included literatures was evaluated using Physiotherapy Evidence Database (PEDro) scale with a mean score of 7.5. Based on the WHO-FICs framework, the types of diseases included intracerebral haemorrhage (8B00), cerebral ischemic stroke (8B11), subarachnoid hemorrhage (8B01), abnormality of tonus and reflex (MB47), and hemiplegia (MB53). The main dysfunctions of the upper extremity after stroke included mobility of joint functions (b710), stability of joint functions (b715), muscle power functions (b730), muscle tone functions (b735), motor reflex functions (b750), control of voluntary movement functions (b760), involuntary movement functions (b765). Activity and participation included activity of upper limb, such as lifting and carrying objects (d430), hand and arm use (d445), and fine hand use (d440); and the daily life activities and social participation, such as self-care (d510-d570), domestic life (d610-d660), major life areas (d810-d879), community, social and civic life (d910-d950). Therapeutic interventions on body functions included electrical stimulation of muscle functions (MU2.SC.BP), assistance and guidance of exercise for involuntary movement reaction (MV2.PG.ZZ); therapeutic interventions involving activity and participation were training in lifting and carrying (SIA.PH.ZZ), training in fine hand use (SIG.PH.ZZ), exercises of arm and hand use (SIJ.PH.ZZ), self care (SM1-SMH), household tasks (SO2-SOD), and playing games (SXD.PH.ZZ); 15 to 60 minutes a time, three to ten times a week, for three to eight weeks, in hospital or at home. The outcomes of the intervention were divided into three levels. At the body function level, patients had improved neuromotor conduction function, reflex function, casual motor control, coordination and speed, joint mobility, and grip strength. At the activity and participation level, there were enhancements in upper limb mobility and speed, fine hand function and speed, frequency and quality of upper limb activity participation, and the capacities of daily living and reduced difficulty in daily activity tasks. In terms of whole functioning, patients had acquired quality of life and well-being and acquainted a feeling of pleasure and accomplishment. ConclusionA PICO framework was constructed for occupational therapy based on WHO-FICs. The health conditions included intracerebral haemorrhage, cerebral ischemic stroke, subarachnoid hemorrhage, abnormality of tonus and reflex, and hemiplegia. Upper extremity motor dysfunction mainly included dysfunction of voluntary motor control, low or hyperactive motor reflexes, abnormalities in muscle tone, impaired muscle coordination, poor stability of joint activities, and reduced muscle strength, etc. Activity limitation and participation restriction were manifested as functioning in the fields of arm and hand activity participation, fine manual activity, and activities of daily living and social participation. Therapeutic interventions at body function level included brain-computer interface-based functional electrical stimulation and unimanual mirror therapy; therapeutic interventions at activity and participation level included action observation training, bimanual mirror therapy, task-oriented training, bilateral arm training and upper extremity robotics training. The health and functional benefits included the improvements in upper extremity motor function, upper extremity mobility and participation levels, activities of daily living and social participation, and quality of life and well-being.

Risk Factors for in-Hospital Mortality in Patients with Takotsubo Syndrome / 中山大学学报(医学科学版)

ObjectiveTo analyze the risk factors for in-hospital mortality in patients with Takotsubo Syndrome （TTS）. MethodsHospitalization data of consecutive patients with TTS from February 2009 to January 2022 were retrospectively collected and analyzed. Patients were divided into survival group and death group according to outcomes. The basic clinical information， triggering factors， laboratory examinations， electrocardiogram， echocardiography， complications and treatments of the two groups were compared. Univariable logistic regression analysis was used to screen the possible risk factors for in-hospital mortality in TTS patients， and multivariable logistic regression analysis was used to determine the independent risk factors for in-hospital mortality in TTS patients. ResultsA total of 62 TTS patients were included in our study， including 21 males （33.9%）， 41 females （66.1%） and 26 postmenopausal women （41.9%）， with the mean age of （55.6±16.2） years， and physical triggers were found in 50 patients （80.6%）. 17 patients （27.4%） died while 45 patients （72.6%） survived during hospitalization. The death group had lower systolic blood pressure and left ventricular ejection fraction （LVEF）， higher incidence rate of syncope， higher level of N-terminal pro-B natriuretic peptide （NT-proBNP） and hypersensitive troponin T （hs TnT） when compared with survival group （all P value <0.05）. As for the triggering factors， the proportion of TTS induced by neurologic disorders in the death group was higher than that in the survival group （P<0.05）. The death group had higher rates of cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， and respiratory failure （all P value <0.05）. Compared with the survival group， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were higher in the death group （all P value <0.05）. Univariable logistic regression analysis suggested that syncope， NT-proBNP， LVEF， neurologic disorders， cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， respiratory failure， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were potential risk factors for in-hospital mortality in TTS patients （all P value <0.05）. Multivariable logistic regression analysis indicated that neurologic disorders ［OR（95%CI）=5.651（1.195，26.715），P=0.029］， atrial fibrillation ［OR（95%CI）=6.217（1.276，30.298）， P=0.024）］ and therapeutic norepinephrin ［OR（95%CI）=8.847（1.912，40.949）， P=0.005］ were independent risk factors for in-hospital mortality in TTS patients. ConclusionsNeurologic disorders， atrial fibrillation and therapeutic norepinephrin are independent risk factors for in-hospital mortality in patients with Takotsubo Syndrome. Clinically， attention should be paid to the prevention and treatment of neurologic disorders and atrial fibrillation； norepinephrine should be carefully used in patients with diagnosed TTS complicated with hemodynamic instability.

Ambient Fine Particulate Matter Exposure and Blood Pressure: Evidence from a Large Chinese Multiple Follow-Up Study / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the association of ambient PM2.5 exposure with blood pressure (BP) at the population level in China.@*METHODS@#A total of 14,080 participants who had at least two valid blood pressure records were selected from the China Health and Retirement Longitudinal Survey during 2011-2015. Their long-term PM2.5 exposure was assessed at the geographical level, on the basis of a regular 0.1° × 0.1° grid over China. A mixed-effects regression model was used to assess associations.@*RESULTS@#Each decrease of 10 μg/m3 in the 1 year-mean PM2.5 concentration (FPM1Y) was associated with a decrease of 1.24 [95% confidence interval (CI): 0.84-1.64] mmHg systolic BP (SBP) and 0.50 (95% CI: 0.25-0.75) mmHg diastolic BP (DBP), respectively. A robust association was observed between the long-term decrease in PM2.5 and decreased BP in the middle-aged and older population. Using a generalized additive mixed model, we further found that SBP increased nonlinearly overall with FPM1Y but in an approximately linear range when the FPM1Y concentration was < 70 µg/m3; In contrast, DBP increased approximately linearly without a clear threshold.@*CONCLUSION@#Efficient control of PM2.5 air pollution may promote vascular health in China. Our study provides robust scientific support for making the related air pollution control policies.

Progress in research of risk prediction of non-syndromic oral clefts using genetic information / 中华流行病学杂志

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.

Humanistic Characteristics and Enlightenment of Life View in Huang Di Nei Jing / 中国医学伦理学

The view of life in Huang Di Nei Jing discusses the essence of human life by exploring the origin, structure and existence of human life, elucidates the overall quality of human life by observing the state and length of human life, and summarizes the characteristics of human life by analyzing the commonalities and unique characteristics of human life with other lives. On the one hand, this life view respects the objectivity and regularity of life, and enabling people to calmly face death but actively seeking higher possibilities of life, which reflects the reasonable self-awareness of ancient doctors towards human life. On the other hand, it affirms the intrinsic value of life, advocates meeting the subjective value of life and pursuing the external value of life, and expresses the self-pursuit of exploring the existence value of human life, which makes the life view in Huang Di Nei Jing quite humanistic. This humanistic life view has important reference significance for modern medical practice. Reasonable absorbing the humanistic spirit of the life view in Huang Di Nei Jing is conducive to the return of modern medicine to the medical essence of saving the dying and healing the wounded, as well as the establishment of the medical value of people-oriented.

Advances of Congenital Alopecia/Hypotrichosis in Genetics Research / 罕见病研究

Congenital alopecia/hypotrichosis is a rare group of monogenic genetic hair disorders characterized by congenital limited or diffuse hair loss and scarcity, without any effective treatment. Genetic testing to identify the causative gene mutation is the gold standard for confirming the diagnosis of this group of disorders. Because of the heterogeneity in clinical features and genetic pattern of this group of diseases, it is very easy to misdiagnose and mistreat them as diffuse baldness or androgenic alopecia and other acquired alopecia, so clinicians should improve their understanding of this group of diseases. With the continuous development of molecular biology techniques in recent years, a variety of causative genes for congenital alopecia/hypotrichosis have been identified so far, and the pathogenesis of some of these genes and their corresponding subtypes have been clarified. In this paper, we reviewed the clinical manifestations and genetic research progress of non-syndromic congenital alopecia/ hypotrichosis, in order to facilitate clinicians' comprehensive understanding of these rare hair diseases and improve clinical diagnosis and treatment.

Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex

Objective@#Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. @*Methods@#We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. @*Results@#Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. @*Conclusion@#Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

Traditional Chinese Medicine Targets mTOR Signaling Pathway for Treatment of Diabetic Kidney Disease： A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD）， a chronic kidney disease with unique pathological structural and functional alterations in the kidney， is a common complication of diabetes mellitus （DM）. The majority of researchers believe that the occurrence of this disease is associated with glucose metabolism disorders， oxidative stress， inflammation， endoplasmic reticulum stress， autophagy， and disorders of lipid metabolism and exosome release. The mammalian target of rapamycin （mTOR） signaling pathway， which can maintain glomerular podocyte homeostasis and participate in autophagy， renal fibrosis， oxidative stress， lipid metabolism disorders， and inflammatory response in DKD， has been discovered to play a key role in DKD. Therefore， it has emerged as a novel target for the treatment of DKD. Studies have demonstrated that traditional Chinese medicine can prevent the renal damage in DKD by regulating the mTOR signaling pathway to delay the disease progression and improve the prognosis and the quality of life of the patients. This article summarizes the structure and role of the mTOR signaling pathway in DKD and briefs the research progress in the prevention and treatment of DKD via this signaling pathway by the active components， extracts， and compound prescriptions of Chinese medicines， aiming to present new ideas and approaches for the clinical treatment of DKD with traditional Chinese medicine.