Prognostic value of sarcopenia in older adults with transcatheter aortic valve implantation: A systematic review and meta-analysis.

OBJECTIVE: We conducted this systematic review and meta-analysis to summarize the prevalence of sarcopenia and its impact on mortality in patients undergoing TAVI. METHOD: Medline, EMBASE, and PubMed were searched from inception to October 14, 2022 to retrieve eligible studies that assessed sarcopenia in patients undergoing TAVI. Pooled sarcopenia prevalence was calculated with 95% confidence interval (CI), and heterogeneity was estimated using the I2 test. Associations of sarcopenia with mortality of post-TAVI were expressed as hazard ratio (HR) or odds ratios (OR) and 95% CI. RESULTS: 13 studies involving 5248 patients (mean age from 78.1 to 84.9 years) undergoing TAVI were included. There were eleven studies defined sarcopenia based on loss of skeletal muscle mass index (SMI), while only two studies used low muscle mass plus low muscle strength and/or low physical performance. Overall, the pooled prevalence of sarcopenia in patients undergoing TAVI was 49% (95% CI 41%-58%). Sarcopenia was associated with an increased risk of long-term (≥1 year) mortality in patients after TAVI (HR 1.57, 95% CI 1.33-1.85, P < 0.001), with similar findings in the subgroups stratified by follow-up time, definition of sarcopenia, study location, and study design. Furthermore, the 1-, 2-, and 3-year cumulative probabilities of survival in patients with sarcopenia were significantly lower than non-sarcopenia (74.0% vs 91.0%, 68.3% vs 78.0%, and 72.6% vs 79.8%, all P < 0.05). CONCLUSIONS: Although there are substantial differences in diagnostic criteria, sarcopenia is highly prevalent in patients undergoing TAVI and its linked to increased long-term mortality after TAVI.

The effect of externally applied traditional Chinese medicine in diabetic foot: A systematic review and meta-analysis of 34 RCTs.

AIM: This study aimed to investigate the clinical efficacy of externally applied Traditional Chinese Medicine (TCM) on diabetic foot. METHODS: We searched the China Knowledge Network (CNKI), Wanfang Database, PubMed and Web of Science from inception to July 31, 2022, to find all randomized control trials (RCTs) related to externally applied TCMs in diabetic foot treatment. Information about the total effective rate, healing rate, and healing time were extracted. In addition, the relative risk (RR)/odds ratio (OR) or standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated. RESULTS: Finally, a total of 34 RCTs including 3758 patients were included in this meta-analysis. There were 5 articles that reported hydropathic compress with astrogalin, 14 articles that reported MEBO burn cream, 9 articles that reported compound cortex phellodendri liquid and 6 articles that reported Shengji Yuhong ointment. Compared with the basic treatment, the externally applied TCM (astrogalin, MEBO burn cream, compound cortex phellodendri liquid and Shengji Yuhong ointment) combined with basic treatment improved the total effective rate (RR = 1.31 [1.20, 1.42], P < 0.0001) and healing rate (RR = 1.84 [1.56, 2.17], P < 0.0001) and shortened the healing time (SMD = - 2.51 [- 3.39, - 1.63], P < 0.0001). CONCLUSION: Our systematic review and meta-analysis revealed that common TCM applied externally could significantly improve the clinical efficacy comparing to the basic treatment.

Prognostic value of temporal muscle thickness, a novel radiographic marker of sarcopenia, in patients with brain tumor: A systematic review and meta-analysis.

Sarcopenia has been identified as a prognostic factor among certain types of cancer. However, it is unclear whether there is prognostic value of temporalis muscle thickness (TMT), a potential surrogate for sarcopenia, in adults patients with brain tumors. Therefore, we searched the Medline, Embase, and PubMed to systematically review and meta-analyze the relationship between TMT and overall survival, progression-free survival, and complications in patients with brain tumors and the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) were evaluated. The quality in prognostic studies (QUIPS) instrument was employed to evaluate study quality. Nineteen studies involving 4570 patients with brain tumors were included for qualitative and quantitative analysis. Meta-analysis revealed thinner TMT was associated with poor overall survival (HR, 1.72; 95% CI, 1.45-2.04; P < 0.01) in patients with brain tumors. Sub-analyses showed that the association existed for both primary brain tumors (HR, 2.02; 95% CI, 1.55-2.63) and brain metastases (HR, 1.39; 95% CI, 1.30-1.49). Moreover, thinner TMT also was the independent predictor of progression-free survival in patients with primary brain tumors (HR, 2.88; 95% CI, 1.85-4.46; P < 0.01). Therefore, to improve clinical decision making it is important to integrate TMT assessment into routine clinical settings in patients with brain tumors.

Buffering effect of positive childhood experiences on mental health risks among adolescents / 中国学校卫生

Objective@#To explore the buffering effect of positive childhood experiences (PCEs) on mental health risks among adolescents before and after COVID-19 epidemic.@*Methods@#In October 2019 (before the outbreak of COVID-19), 1 322 students from grades 4 to 9 were recruited from primary and secondary schools in two counties of Chizhou city, Anhui Province. A questionnaire survey was conducted to collect general demographic information, PCEs, depressive symptoms, anxiety symptoms, self harm behavior, suicidal ideation. Follow up survey was conducted after school re opening (May 2020). Mental health status before and after the COVID-19 epidemic was compared among students with different PCEs by multiple logistic regression analyses.@*Results@#The detection rates of depressive symptoms, anxiety symptoms, self harm behavior and suicidal ideation (22.6%, 16.0%, 40.0%, 29.9%) of the respondents after school re opening were significantly higher compared that before the epidemic (16.5%, 13.5%, 31.1 %, 22.6%). There were no significant differences in the detection rates of depressive symptoms, anxiety symptoms,self harm behavior and suicidal ideation between high PCEs group before and after the epidemic ( Z =-0.05,0.27,0.84,1.84, P >0.05). Multivariate Logistic regression analysis showed that the risk of depressive symptoms and self harm behavior in the low PCEs group after school re opening was 1.39 times higher than that before the epidemic (95% CI= 1.05 -1.84, P <0.05). The risk of non suicidal self injury behavior in the low PCEs group after school re opening was 1.31 times higher than that before the epidemic (95% CI= 1.05 -1.62, P <0.05). There were no significant differences in mental health detection rates in high PCEs group before and after the epidemic ( P >0.05).@*Conclusion@#During the time of COVID-19 epidemic, PCEs is associated with lower rates of depressive symptoms, anxiety symptoms, self harm behavior and suicide ideation in adolescents. The findings suggest that more support and help should be given to adolescents from the perspectives of family, school and peers, so as to reduce the adverse effects of public health emergencies on adolescents mental health.

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.

Forensic Analysis of Sudden Death Associated with Sexual Activity.

OBJECTIVES: To analyze the characteristics of sudden death associated with sexual activity to provide recommendations for forensic identification. METHODS: A retrospective analysis was conducted on autopsy cases accepted by Forensic Identification Center of Huazhong University of Science and Technology from 1998 to 2018, and a total of 15 cases of sudden death associated with sexual activity were screened out. The general information, case data and pathological changes of 15 cases were collected to find the relationship between sexual activity and sudden death. RESULTS: The ratio of male to female was 1.5∶1. The average age of males was 50.1 years and that of females was 35.0 years. Coronary artery diseases and brain diseases accounted for most of the cases (12/15). Sexual partners were associated with locations of deaths and body dumping behaviors. CONCLUSIONS: Sudden death associated with sexual activity, although rare, may occur in people over 30 years old with pre-existing heart or brain diseases, which should be paid attention to in forensic practice.

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients.

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.

Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques.

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.

Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2.

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.

Comparison of various lipid parameters in association of target organ damage: a cohort study.

BACKGROUND: Recommendations of non-HDL amplification varied from different guidelines. We aim to test the relationships between various lipid parameters and target organ damage (TOD) including aortic stiffness, peripheral arterial disease and chronic kidney disease in a community-based elderly cohort. METHODS: 1599 (aged 71.4 ± 6.1 years) participants were recruited. Eight lipid parameters, including total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, non-HDL-C, TC/HDL ratio, TG/HDL ratio and LDL/HDL ratio, together with other plasma biomarkers like creatinine were measured. Pulse wave velocity (PWV) was measured by the SphygmoCor device, and ankle-brachial index (ABI) was assessed by Omron VP-1000 device. RESULTS: Four individual lipid parameters (TC, TG, LDL-C and HDL-C) significantly correlated with most, but not all, TOD indices. Meanwhile, 4 combined lipid parameters, namely non-HDL-C, TC/HDL, TG/HDL and LCL/HDL, significantly correlated with all TOD (P ≤ 0.033). In multiple linear regression analyses, 4 combined lipid parameters also significantly associated with TOD (P ≤ 0.027), while none of individual lipid parameters significantly associated with all TOD indices. In multiple logistic regression analyses, only non-HDLC and TC/HDL significantly associated with TOD (P ≤ 0.039), and other lipid parameters did not significantly associate with TOD. CONCLUSION: In an elderly community sample, non-HDLC and TC/HDLC were better associated with TOD than other lipid parameters. This finding should be considered in future clinical lipid-lowing therapy. TRIAL REGISTRATION: This trial was retrospectively registered in ClinicalTrials.gov (No. NCT02368938 , registered on 15 Feb 2015).

The influence of intracellular keratin 8 on hepatitis C virus replication / 药学学报

The level of intracellular keratin 8(KRT-8) is associated with liver diseases, whose expression is increased in hepatitis C virus (HCV)-infected patients with hepatocarcinoma and in cultural cells infected with HCV. However, it is not clear whether KRT-8 will impact HCV replication. In this paper, the HCV replication was analyzed in response to high expression and silence of KRT-8. The inhibitory activities against wild-type and mutant HCV were also analyzed by silence of KRT-8 or combined with known anti-HCV drug telaprevir. Results showed that the protein level of KRT-8 was increased in proportion with the HCV replication. The high expression was found to facilitate HCV replication, while the silence of KRT-8 was able to inhibit HCV replication and enhanced the anti-HCV activity of telaprevir. It also inhibited A156T and D168V mutant HCV, which are resistant to protease inhibitors. These results suggest that KRT-8 is a co-factor for HCV replication. Down-regulation of KRT-8 can inhibit wild type and mutant HCV replication to enhance the anti-HCV activity of known anti-HCV drugs. Therefore, KRT-8 may be a new target in the development of anti-HCV agents.

[Magnetic resonance diffusion tensor imaging for diagnosis of pyramidal tract damage in rats].

OBJECTIVE: To explore the applicability of magnetic resonance diffusion tensor imaging (DTI) for diagnosis of pyramidal tract damage in rats. METHODS: Marmarou's model was set up, followed by DTI scanning at 3, 12, 24 and 72 h post trauma to acquire the dispersion parameter of bilateral pyramidal tracts. Moreover, axonal varicosities per square millimeter and the percentage of positive area of axons demonstrated by beta-amyloid precursor protein (beta-APP) immunostaining were obtained, as well as the mean density and sum density of neurofilament (NF) 68 immunostaining. RESULTS: Axial diffusivity (AD), fraction anisotropy (FA) and relative anisotropy (RA) in the pyramidal tract were significantly and continuously reduced and reached to the bottom at 72h post trauma (P < 0.05) in accord with the gradient of axonal damage verified by beta-APP and NF68 immunostaining. Furthermore, the changes of AD, FA and RA showed a significant negative correlation with the beta-APP immunohistochemical results. CONCLUSION: DTI has important value for early diagnosis in pyramidal tract damage.

[Advance in animal models of traumatic brain injury].

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Animal models of TBI are used to elucidate primary and secondary injury mechanisms and pathophysiological changes and to provide the diagnostic and therapeutical basis for TBI. The choices of animal models depend upon the research objectives. However, various animal models have limitations. The models only can duplicate the pivotal injury mechanisms or a certain important pathophysiological course. The characteristics of human TBI can not fully be reflected by using these models. In the review, animal models of traumatic brain injury are classified as dynamic direct brain injury, indirect dynamic brain injury and combined neuro-traumatic models. Several common models are described for consideration.

[Study on electrical current mark with environmental scanning electron microscopy and energy dispersive X-ray microanalyser].

OBJECTIVE: To provide objective proof on diagnosis of electrical current mark in electrocution, the environmental scanning electron microscopy and energy dispersive X-ray microanalyser (ESEM-EDX) were adopted to study the microscopic morphological characteristics and elemental composition of electrical current mark. METHODS: Morphological characteristics of electrical current marks, the elemental composition and morphology of metal particles were studied with ESEM-EDX. RESULTS: The electroporation and metal melted beads could be found in the electrical current marks and skin around them. The metal melted beads mainly composed of common metal such as iron, copper, aluminum and some uncommon metal including gold, titanium and barium. CONCLUSION: ESEM-EDX can be applied in forensic diagnosis of electrocution.

[Study on the expression of matrix metalloproteinase-9 in lung fibroblasts of rat with acute paraquat poisoning].

OBJECTIVE: To investigate the expression and effect of matrix metaloproteinases-9 in lung injury of rats with acute paraquat poisoning. METHODS: 50 SD rats were randomly divided into control group and poisoned group. At 1, 3, 7, 14, 28 days after exposed to paraquat, five rats of each group were used to assess lung pathological changes, and the expression of MMP-9 mRNA in lungs was evaluated by RT-PCR. RESULTS: (1) The expressions of MMP-9 protein and mRNA markedly increased at the first day of paraquat poison, reached the peak at the 7th day, decreased slowly afterwards. (2) The expressions of MMP-9 protein and mRNA markedly increased at 1, 3, 7 days. The protein expression of MMP-9 returned to baseline level at the 28th day, and mRNA expression of MMP-9 returned to baseline at the 14th day. CONCLUSION: The expression of MMP-9 in lung fibroblasts is up-regulated in silicotic fibrosis model.

[Application of immunofluorescence and sandwich ELISA with double-antibodies in detection of human rabies].

OBJECTIVE: To explore the application of immunofluorescence and sandwich ELISA with double-antibodies in detection of human rabies. METHODS: The cerebrum, cerebellum, brainstem, and hippocampus of four patients died of rabies identified by clinical diagnosis were collected and kept in freezer at -70 degrees C or in formaldehyde solution separately. The rat brain tissue infected by CVS strain of rabies virus was used as a positive control and the brain tissue of a patient died of acute pancreatitis was used as a negative control. RESULTS: Rabies virus was detected in the tissues kept in freezer at -70 degrees C and the positive control but was not detected in the tissues kept in formaldehyde solution and the negative control. CONCLUSION: Immunofluorescence and Sandwich ELISA with double-antibodies could be used in detection of human rabies. The samples should be kept in deep frozen temperature condition instead of in formaldehyde solution.

[Recent progress in epilepsy in neuropathology].

Epilepsy is a common cerebral disease, and may cause sudden death. Although electric activity study of epileptic brain had been emphasized in the past, the neuropathological study of epilepsy has become a main focus in clinical and forensic medicine recently. This article reviews the recent progress in neuropathology of epilepsy including developmental disorder, abnormal tumoral proliferation, hippocampal sclerosis, dual pathological alteration, and mossy fiber sprouting. Its significance in forensic medicine, particularly for the diagnosis of sudden unexpected death in epilepsy, is discussed.

[Changes of cyclin D1 expression following human brain contusion].

OBJECTIVE: To study the relationships of Cyclin D1 expression with the posttraumatic intervals (PTI) following the cerebra, brainstem or cerebella contusion in human. METHODS: 88 cases of brain contusions of the closed head injury were investigated with pathological and Cyclin D1 immunohistochemistry methods. The results were analyzed by image analysis technique (IAT). RESULTS: The immunoreactivity of Cyclin D1 was almost disappeared in the core cells of the brain contusion. Cyclin D1-positive cells started to increase in the boundary of the brain contusion in the 1h group. Cyclin D1-positive cells were increased significantly in the 3 h-30 d groups and maintained at a high level in the boundary of the brain contusion of those groups. It is suggested that the Cyclin D1-positive cells were primarily origin from microglia and other glia. A few neurons expressed Cyclin D1. CONCLUSION: Cyclin D1 can express in several kinds of brain cells following the contusion, especially in the glia cells. Cyclin D1-positive cells were increased obviously and rapidly after injury, so it could be used as a reference marker for early stage brain injury.

[Relationship between expression of nestin in experimental brain contusion and injury time].

OBJECTIVE: To observe the alteration of nestin intervals in the experimental traumatic brain injury and investigate its relation to the injury intervals. METHODS: The rat brain contusion was conducted by falling impact injury. After various survival interval (0.5, 6, 12 h and 1, 3, 7, 14, 28 d), immunohistochemical SP method was used for observing the expression of nestin in the cortex, hippocampal dentate gyrus and the corpus callosum on injury side. RESULTS: Expression of nestin positive cells increased at 0.5 h and reached the maximum level in 7 d after brain contusion, then the expression decreased gradually. The intensity of nestin staining in the the cortex and the hippocampal dentate gyrus decreased to normal on 28 d. As to the corpus callosum of injury side it remained weak on 28 d. CONCLUSION: The changes of nestin immunohistochemical staining can be used as an index for forensic estimation of early injury time.