Objective:To explore Lijin Zhenggu Therapy combined with heat supplementing needles on cartilage damage, immune balance, and liver X receptor NF-κB in knee osteoarthritis of New Zealand white rabbits.Methods:Totally　60 New Zealand white rabbits were divided into normal group, model group, Lijin Zhenggu Therapy group, heat supplementing needles group, and a combination group using random number table method, with 12 rabbits in each group. Except for the normal group, all other groups were established with knee osteoarthritis models. The Lijin Zhenggu Therapy group was treated with Lijin Zhenggu Therapy, the heat supplementing needles group was treated with heat supplementing needles, the combination group was treated with Lijin Zhenggu Therapy combined with heat supplementing needles. The pain threshold of each group of white rabbits was observed using a pain meter; HE staining was used to observe the morphology of cartilage damage in each group of white rabbits; ELISA was used to detect PGE 2, IL-1β and β-EP in the articular cartilage tissue of white rabbits in each group; PCR was used to detect the levels of LXRα and NF-κB mRNA. Western blot was used to detect toll like receptor 4 (TLR4), myeloid differentiation factor (MyD88), interferon regulatory factor-7 (IRF-7) in synovial tissue of rabbits in each group. Results:Compared with model group, the pain threshold of rabbits in heat supplementing needles group, Lijin Zhenggu Therapy group and combination group increased ( P<0.05); the levels of PGE 2 and IL-1β decreased ( P<0.05), while the level of β-EP increased ( P<0.05). LXRα mRNA level increased ( P<0.05), and NF-κB mRNA level decreased ( P<0.05); the expressions of TLR4, MyD88, IRF-7 and NF-κB P65 in synovial tissue decreased ( P<0.05). Conclusions:Lijin Zhenggu Therapy combined with heat supplementing needles can reduce the levels of PGE 2 and IL-1β, increase β-EP level, improve pain and cartilage tissue morphology. The mechanism may be related to the regulation of liver X receptor nuclear factor NF-κB pathway, reduction of inflammatory reactions and immunity maintaining.

Aim To analyze the risk factor of the cardiac rupture(CR)in patients with acute ST-segment eleva-tion myocardial infarction(STEMI).Based on this,the nomogram model of acute STEMI patients with CR was estab-lished.Methods Through Ningxia Medical University General Hospital's big data research platform and hospital in-formation system retrieval,5 412 patients with acute STEMI from January 2015 to December 2019 were continuously includ-ed in the study,of which 91 patients with CR were included as CR group;5 321 patients non-combined with CR were in-cluded as non-CR group.LASSO regression,univariate and multivariate Logistic regression were used to analyze the risk factors of CR in patients with acute STEMI,and the CR nomogram predictive model was established.The nomogram mod-el was validated and evaluated by using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test and clinical decision curve analysis(DCA).Results LASSO regression results showed that age,female,hypertension history,first medical contact time,shock index,Killip grade,white blood cell count,d-dimer,lactic acid,anterior myocardial in-farction,β-blocker administration within 24 hours,angiotensin converting enzyme inhibitor/angiotensin receptor antagonist(ACEI/ARB)administration within 24 hours,emergency percutaneous coronary intervention(PCI)were 13 risk factors of CR(P＜0.05).The screened 13 risk factors were analyzed by univariate and multivariate Logistic regression,the results suggested that age,Killip grade,first medical contact time,white blood cell count,not undergoing emergency PCI and not taking ACEI/ARB drugs within 24 hours were the risk factors of CR in patients with acute STEMI.The acute STEMI with CR nomogram model was established according to the above 6 risk variables.The area under the ROC curve before and after the internal verification of the nomogram model was 0.946(95％CI:0.927～0.961),0.947(95％CI:0.927～0.959),and the sensitivity was 0.957 and 0.904,respectively,the specificity was 0.858 and 0.876,respectively,which indicated that the model had good discrimination degree.The Hosmer-Lemeshow test showed that the deviation between the predicted value and the observed value was not statistically significant(x2=12.70,P=0.122),indicating that the no-mogram model had a good calibration.The DCA curve indicated that the predictive probability threshold of the model was from 0.00 to 0.40,and the clinical net benefit was the highest,indicating that the model had good clinical efficacy.Conclusion The nomogram model established in this study has better distinction,calibration and clinical effectiveness.It can effectively predict the probability of acute STEMI with CR,and provide some help for clinical diagnosis and treat-ment,so as to reduce the incidence of CR.

Purpose To evaluate the effect of PCSK9 gene knockout on myocardial function in obese mice via ultrasound strain technology,and to discuss the related mechanisms.Materials and Methods Twenty six-week-old wild-type C57BL/6 male mice were selected and randomly divided into a normal group(n=10)and an obese group(n=10).Additionally,ten six-week-old PCSK9-/-C57BL/6 male mice were selected as the PCSK9-/-group.Mice in the obese group and PCSK9-/-group were fed with high-fat feed to create models,while those in the normal group were fed with regular feed.After 12 weeks,mice that were successfully modeled were selected from the obese group and PCSK9-/-group.Then,the three groups of mice were subjected to cardiac ultrasound,transmission electron microscopy and immunofluorescence staining to observe relevant indicators.Results The interventricular septal end-diastolic thickness of mice in obese group,normal group,and PCSK9-/-group were(0.98±0.13)mm,(0.77±0.07)mm,(0.78±0.13)mm,respectively,with statistically significant difference(F=5.10,P=0.02).The obese group was thicker than the normal group(t=2.73,P＜0.05),while the PCSK9-/-group was thinner than the obese group(t=-2.92,P＜0.05).There were statistically significant differences in global longitudinal strain and global circumferential strain of the left ventricle among the three groups(F=7.44,15.40,P＜0.05),with the obese group showing a decrease in global longitudinal strain and global circumferential strain compared to the normal group(t=3.79,5.50,P＜0.05).The PCSK9-/-group showed an increase in global longitudinal strain and global circumferential strain compared to the obese group(t=-2.53,-3.37,P＜0.05).Electron microscopy and immunofluorescence results showed that the myocardial ultrastructure of the obese group was damaged,and the expression of NLRP3 and Caspase-1 were higher than that of the normal group(t=12.53,-4.73,P＜0.05),the myocardial ultrastructure damage in the PCSK9-/-group was significantly improved,the expression of NLRP3 and Caspase-1 were lower than that in the obese group(t=-6.23,2.05,P＜0.05).Conclusion Ultrasound strain can more sensitively detect changes in myocardial function in obese mice with PCSK9 gene knockout compared with conventional cardiac ultrasound parameters.Knockout of the PCSK9 gene may improve myocardial function in obese mice by inhibiting the expression of NLRP3 and Caspase-1.

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate. ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD. MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors. ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P<0.05 or 0.01）. Multiple linear regression analysis denoted that the average weekly hours of home-based intervention in the first three months had certain effect on listener responds （β=1.029， P<0.05）. ConclusionApplication of home-based early intensive behavior intervention using VB-MAPP may contribute to the improvement of verbal abilities such as mand， tact and listener responds in children with ASD. ［Funded by 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund （number， 20200601）］

‍Nonalcoholic fatty liver disease （NAFLD） is a group of highly heterogeneous diseases closely associated with metabolic dysfunction. Sarcopenia is a syndrome caused by a continuous decline in muscle mass， strength， and function， and it is often accompanied by NAFLD. Insulin resistance is the main pathological mechanism for sarcopenia and NAFLD， and in addition， factors such as changes in proteins and branched‍-‍chain amino acid， hyperammonemia， intestinal flora， and endocrine dysfunction can also lead to sarcopenia and NAFLD. With the deepening of clinical research， many published prospective studies have confirmed the existence of a bidirectional and complex pathophysiological relationship between sarcopenia and NAFLD. This article reviews the bidirectional relationship between sarcopenia and NAFLD， discusses the common pathogenesis of sarcopenia and NAFLD， summarizes the challenges faced in this field， and proposes new directions for the research on the bidirectional relationship between NAFLD and sarcopenia.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

Objective:To investigate the risk factors for combined coronary microvascular dysfunction (CMD) in patients with ischemia and non-obstructive coronary artery disease (INOCA).Methods:From October 2020 to May 2022, 100 INOCA patients with myocardial ischemic symptoms who underwent coronary angiography (CAG) suggestive of <50% stenosis in all three coronary arteries at the Tenth People′s Hospital of Tongji University were prospectively recruited. Myocardial perfusion imaging (MPI), transthoracic echocardiography and cadmium-zinc-telluride (CZT) SPECT coronary flow quantification were performed in the same month, and 93 INOCA patients (36 males and 57 females, age (63.0±10.9) years) were finally included. CMD was defined as coronary flow reserve (CFR)<2.5. Independent-sample t test, Mann-Whitney U test and χ2 test were used to compare MPI results and left ventricular volume parameters between CMD and non-CMD groups. ROC curve analysis was used to analyze the efficacy of each index in predicting CMD, and independent risk factors for CMD were screened by multivariate logistic regression analysis. Results:Among 93 INOCA patients, 29 were in the CMD group and 64 were in the non-CMD group. The age, proportion of hypertension, left ventricular mass index (LVMI), summed stress score (SSS), summed difference score (SDS), left ventricular internal diameter systolic (LVIDS), interventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) in the CMD group were higher than those in the non-CMD group ( t values: 2.42-3.76, χ2=8.94, z values: -3.31, -3.41, all P<0.05). ROC curve analysis showed that LVMI, SSS, SDS, LVPWT, IVST and age were significant in predicting CMD (AUCs: 0.67-0.72). Multivariate logistic regression analysis showed that LVMI (odds ratio ( OR)=1.08, 95% CI: 1.01-1.17), SDS ( OR=5.37, 95% CI: 1.95-14.78), hypertension ( OR=5.68, 95% CI: 1.34-24.18) and age ( OR=1.10, 95% CI: 1.03-1.18) were risk factors for CMD. Conclusion:LVMI, SDS, hypertension and age are strongly associated with combined CMD in INOCA patients, which can be used for early risk stratification of INOCA patients.

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) combined with modified neurolysis in treatment of diabetic foot ulcer (DFU) through a prospective randomized controlled study. METHODS: The patients with DFU and diabetic peripheral neuropathy, who were admitted between February 2020 and February 2022, were selected as the research objects, of which 31 cases met the selection criteria and were included in the study. The patients were divided into two groups by random number table method. The 15 patients in the trial group were treated with TTT combined with modified neurolysis, and the 16 patients in the control group received treatment with TTT alone. There was no significant difference in gender, age, duration of DFU, ulcer area, Wagner classification, as well as preoperative foot skin temperature, visual analogue scale (VAS) score, ankle-brachial index (ABI), motor nerve conduction velocity (MNCV) of the common peroneal nerve, MNCV of the tibial nerve, MNCV of the deep peroneal nerve, two-point discrimination (2-PD) of heel, and cross-sectional area (CSA) of the common peroneal nerve between the two groups ( P>0.05). The time for ulcer healing, foot skin temperature, VAS scores, ABI, 2-PD of heel, and CSA of the common peroneal nerve before operation and at 6 and 12 months after operation were recorded and compared between groups. The differences in MNCV of the common peroneal nerve, MNCV of the tibial nerve, and MNCV of the deep peroneal nerve between pre-operation and 12 months after operation were calculated. RESULTS: All patients in both groups were followed up 12-24 months (mean, 13.9 months). The surgical incisions in both groups healed by first intention and no needle tract infections occurred during the bone transport phase. Ulcer wounds in both groups healed successfully, and there was no significant difference in the healing time ( P>0.05). During the follow-up, there was no ulcer recurrences. At 12 months after operation, the MNCV of the common peroneal nerve, the MNCV of the tibial nerve, and the MNCV of the deep peroneal nerve in both groups accelerated when compared to preoperative values ( P<0.05). Furthermore, the trial group exhibited a greater acceleration in MNCV compared to the control group, and the difference was significant ( P<0.05). The foot skin temperature, VAS score, ABI, 2-PD of heel, and CSA of the common peroneal nerve at 6 and 12 months after operation significantly improved when compared with those before operation in both groups ( P<0.05). The 2-PD gradually improved over time, showing significant difference ( P<0.05). The 2-PD of heel and VAS score of the trial group were superior to the control group, and the differences were significant ( P<0.05). There was no significant difference in ABI, foot skin temperature, and CSA of the common peroneal nerve between groups after operation ( P>0.05). CONCLUSION Compared with TTT alone, the TTT combined with modified neurolysis for DFU can simultaneously solve both microcirculatory disorders and nerve compression, improve the quality of nerve function recovery, and enhance the patient's quality of life.
Humans ; Diabetic Foot/surgery* ; Microcirculation ; Prospective Studies ; Quality of Life ; Treatment Outcome ; Diabetes Mellitus

Objective To explore the specific plasma exosomal protein expression in Coronary Heart Disease(CHD)with phlegm-turbidity syndrome(PTS),so as to provide biological reference for the diagnosis of CHD with PTS.Methods A total of 20 CHD patients with PTS and 20 healthy subjects at the same period were included.Plasma exosomes were extracted from all subjects using the qEV size exclusion method.First,10 CHD cases with PTS and 10 healthy subjects were randomly selected,and differentially expressed proteins between the two groups were screened using label free non-targeted protein quantification analysis.Then,MRM targeting protein labeling technique was applied to verify the differentially expressed proteins in the remaining subjects.Results Compared with healthy controls,214 differentially expressed plasma exosomal proteins(61 up-regulated and 153 down-regulated)were found in CHD patients with PTS,mainly related to cholesterol metabolism,complement and coagulation cascade,and immune effects.ANXA6,C4BPB,F8,CFB,APOE,C9,and CLU proteins were further validated by MRM targeting protein.Conclusion CHD patients with PTS had differences in plasma exosomal protein expression from healthy controls,and the differential proteins are mainly related to cholesterol metabolism,complement,and the coagulation cascade.

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion