Stability and integrity of self-assembled bovine parvovirus virus­like particles (BPV­VLPs) of VP2 and combination of VP1VP2 assisted by baculovirus-insect cell expression: a potential logistical platform for vaccine deployment.

BACKGROUND: Bovine parvovirus (BPV) is an autonomous DNA virus with a smaller molecular size and subtle differences in its structural proteins, unlike other animal parvoviruses. More importantly, this virus has the potential to produce visible to silent economic catastrophes in the livestock business, despite receiving very little attention. Parvoviral virus-like particles (VLPs) as vaccines and as logistical platforms for vaccine deployment are well studied. However, no single experimental report on the role of VP1 in the assembly and stability of BPV-VLPs is available. Furthermore, the self-assembly, integrity and stability of the VLPs of recombinant BPV VP2 in comparison to VP1 VP2 Cap proteins using any expression method has not been studied previously. In this study, we experimentally evaluated the self-assembling ability with which BPV virus-like particles (VLPs) could be synthesized from a single structural protein (VP2) and by integrating both VP2 and VP1 amino acid sequences. METHODS: In silico and experimental cloning methods were carried out. His-tagged and without-His-tag VP2 and V1VP2-encoding amino acid sequences were cloned and inserted into pFastbacdual, and insect cell-generated recombinant protein was evaluated by SDS‒PAGE and western blot. Period of infectivity and expression level were determined by IFA. The integrity and stability of the BPV VLPs were evaluated by transmission electron microscopy. The secondary structure of the BPV VLPs from both VP2 and V1VP2 was analyzed by circular dichroism. RESULTS: Our findings show that VP2 alone was equally expressed and purified into detectable proteins, and the stability at different temperatures and pH values was not appreciably different between the two kinds of VLPs. Furthermore, BPV-VP2 VLPs were praised for their greater purity and integrity than BPV-VP1VP2 VLPs, as indicated by SDS‒PAGE. Therefore, our research demonstrates that the function of VP1 has no bearing on the stability or integrity of BPV-VLPs. CONCLUSIONS: In summary, incredible physiochemically stable BPV VP2-derived VLPs have been found to be promising candidates for the development of multivalent vaccines and immunodiagnostic kits against enteric viruses and to carry heterogeneous epitopes for various economically important livestock diseases.

U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study.

Context: Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1. Objective: The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET). Methods: We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis. Results: A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. Conclusions: There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.

Efficacy of electroacupuncture on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the efficacy of electroacupuncture (EA) intervention on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Eight databases, including PubMed, Embase, the Cochrane Library, Web of Science, Chinese BioMedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Data, China Science and Technology Journal Database, and two clinical trial registries, were searched. All randomized controlled trials (RCTs) related to EA intervention in cardiac surgery with CPB were collected. Based on the inclusion and exclusion criteria, two researchers independently screened articles and extracted data. After the quality evaluation, RevMan 5.3 software was used for analysis. RESULTS: Fourteen RCTs involving 836 patients were included. Compared with the control treatment, EA significantly increased the incidence of cardiac automatic rebeat after aortic unclamping [relative risk (RR) = 1.15, 95% confidence interval (CI) (1.01, 1.31), P < 0.05; moderate]. Twenty-four hours after aortic unclamping, EA significantly increased the superoxide dismutase [standardized mean difference (SMD) = 0.96, 95% CI(0.32, 1.61), P < 0.05; low], and interleukin (IL)-2 [SMD = 1.33, 95% CI(0.19, 2.47), P < 0.05; very low] expression levels and decreased the malondialdehyde [SMD =－1.62, 95% CI(－2.15, －1.09), P < 0.05; moderate], tumour necrosis factor-α [SMD = －1.28, 95% CI(－2.37, －0.19), P < 0.05; moderate], and cardiac troponin I [SMD = －1.09, 95% CI(－1.85, －0.32), P < 0.05; low] expression levels as well as the inotrope scores [SMD = －0.77, 95% CI(－1.22, －0.31), P < 0.05; high]. There was no difference in IL-6 and IL-10 expression levels. The amount of intraoperative sedative [SMD = -0.31, 95% CI(－0.54, －0.09), P < 0.05; moderate] and opioid analgesic [SMD = -0.96, 95% CI(－1.53, －0.38), P < 0.05; low] medication was significantly lower in the EA group than in the control group. Moreover, the postoperative tracheal intubation time [SMD = －0.92, 95% CI(－1.40, －0.45), P < 0.05; low] and intensive care unit stay [SMD = －1.71, 95% CI(－3.06, －0.36), P < 0.05; low] were significantly shorter in the EA group than in the control group. There were no differences in the time to get out of bed for the first time, total days of antibiotic use after surgery, or postoperative hospital stay. No adverse reactions related to EA were reported in any of the included studies. CONCLUSIONS: In cardiac surgery with CPB, EA may be a safe and effective strategy to reduce myocardial ischaemia-reperfusion injury and speed up the recovery of patients after surgery. These findings must be interpreted with caution, as most of the evidence was of low or moderate quality. More RCTs with larger sample sizes and higher quality are needed to provide more convincing evidence.

Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice.

OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg; 30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg; 30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphine-induced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency (T0) and post-treatment latency (T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase (NOS) activity and nitric oxide (NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-D-aspartate (NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups (5, 10, 20 µmol/L, respectively). Except for the control group, cells were treated with NMDA (HT-22 cells: 20 mmol/L; HEK-293 cells: 50 µmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency (0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE (0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord (0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells (0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. CONCLUSIONS: Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.

Microfluidic integrated D-shaped optical fiber SERS probe with high sensitivity and ability of multi-molecule detection.

In order to enhance the sensitivity, integration, and practical application capability of Raman detection systems, we propose a multi-channel microfluidic integrated D-shaped optical fiber SERS (Surface-enhanced Raman scattering) probe structure. Firstly, a microfluidic polydimethylsiloxane (PDMS) channel was fabricated using a self-designed multi-channel microfluidic template. Secondly, a uniform layer of silver nanoparticles was deposited on the D-shaped optical fiber using the liquid-liquid interface method. Finally, the D-shaped optical fiber was plasma-bonded to the multi-channel microfluidic channel and a cover glass, resulting in a microfluidic integrated D-shaped optical fiber SERS probe. The prepared sample exhibited excellent detection performance for R6G (rhodamine 6 G) with a detection limit as low as 10-11 mol/L and an enhancement factor of 1.14 × 109. Moreover, the multi-channel configuration enables simultaneous detection of multiple molecules, demonstrating excellent multi-channel multiplexing capability.

Open nanocavity-assisted Ag@PDMS as a soft SERS substrate with ultra-sensitivity and high uniformity.

To achieve high sensitivity and uniformity simultaneously in a surface-enhanced Raman scattering (SERS) substrate, this paper presents the preparation of a flexible and transparent three-dimensional (3D) ordered hemispherical array polydimethylsiloxane (PDMS) film. This is achieved by self-assembling a single-layer polystyrene (PS) microsphere array on a silicon substrate. The liquid-liquid interface method is then used to transfer Ag nanoparticles onto the PDMS film, which includes open nanocavity arrays created by etching the PS microsphere array. An open nanocavity assistant soft SERS sample, "Ag@PDMS," is then prepared. For electromagnetic simulation of our sample, we utilized Comsol software. It has been experimentally confirmed that the Ag@PDMS substrate with silver particles of 50 nm in size is capable of achieving the largest localized electromagnetic hot spots in space. The optimal sample, Ag@PDMS, exhibits ultra-high sensitivity towards Rhodamine 6 G (R6G) probe molecules, with a limit of detection (LOD) of 10-15 mol/L, and an enhancement factor (EF) of ∼1012. Additionally, the substrate exhibits a highly uniform signal intensity for probe molecules, with a relative standard deviation (RSD) of approximately 6.86%. Moreover, it is capable of detecting multiple molecules and can perform real detection on non-flat surfaces.

Treatment of Liver Fibrosis after Hepatitis B with TCM Combined with NAs Evaluated by Noninvasive Diagnostic Methods: A Retrospective Study.

Objective. Chronic hepatitis B liver fibrosis is an important intermediate link in the development of liver cirrhosis. A retrospective cohort study was conducted in Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine in order to prove whether integrated traditional Chinese and Western medicine could improve the incidence of CHB complications and clinical prognosis. There are 130 patients with hepatitis B liver fibrosis (being treated from 2011-2021) included in the study, and the patients were divided into 64 TCM users (NAs combined with TCM) and 66 TCM nonusers (NAs antiviral therapy). The serum noninvasive diagnostic model (APRI, FIB-4) and LSM value were used to classify the stages of fibrosis. The results showed that the LSM value was decreased significantly in TCM users compared with TCM nonusers (40.63% versus 28.79%). Indicators of FIB-4 and APRI of TCM users have improved significantly compared with that of TCM nonusers (32.81% versus 10.61% and 35.94% versus 24.24%). The AST, TBIL, and HBsAg levels in TCM users were lower than those in TCM nonusers, and the HBsAg level was inversely correlated with the CD3+, CD4+, and CD8+ in TCM users. The PLT and spleen thickness of TCM users also were improved considerably. The incidence rate of end-point events (decompensated cirrhosis/liver cancer) in TCM nonusers was higher than that of TCM users (16.67% versus 1.56%). The long course of the disease and a family history of hepatitis B were the risk factors for disease progression, and long-term oral administration of TCM was the protective factor. As a result, the serum noninvasive fibrosis index and imaging parameters in TCM users were lower than those of TCM nonusers. Patients in the treatment of NAs combined with TCM had better prognoses such as a lower HBsAg level, a more stable lymphocyte function, and a lower incidence of end-point events. The present findings suggest the effect of TCM combined with NAs in the treatment of chronic hepatitis B liver fibrosis is better than that of single drug treatment.

Plasmonic volcano-like fiber-optic probe for Raman enhancement.

Light-matter interaction is a fascinating topic extensively studied from classical theory, based on Maxwell's equations, to quantum optics. In this study, we introduce a novel, to the best of our knowledge, silver volcano-like fiber-optic probe (sensor 1) for surface-enhanced Raman scattering (SERS). We employ the emerging quasi-normal mode (QNM) method to rigorously calculate the Purcell factor for lossy open system responses, characterized by complex frequencies. This calculation quantifies the modification of the radiation rate from the excited state e to ground state g. Furthermore, we use and extend a quantum mechanical description of the Raman process, based on the Lindblad master equation, to calculate the SERS spectrum for the plasmonic structure. A common and well-established SERS probe, modified by a monolayer silver nanoparticle array, serves as a reference sensor (sensor 2) for quantitatively predicting the SERS performance of sensor 1 using quantum formalism. The predictions show excellent consistency with experimental results. In addition, we employ the FDTD (finite-difference time-domain) solver for a rough estimate of the all-fiber Raman response of both sensors, revealing a reasonable range of SERS performance differences compared to experimental results. This research suggests potential applications in real-time, remote detection of biological species and in vivo diagnostics. Simultaneously, the developed FDTD and quantum optics models pave the way for analyzing the response of emitters near arbitrarily shaped plasmonic structures.

Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

Cognitive and Brain Gray Matter Changes in Children with Obstructive Sleep Apnea: A Voxel-Based Morphological Study.

BACKGROUND: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and clinical severity indicator of children with OSA. METHODS: Twenty-seven children with OSA (7.6 ± 2.5 years, apnea hypopnea index [AHI]: 9.7 ± 5.3 events/h) and 30 healthy controls (7.8 ± 2.6 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent 3.0 T magnetic resonance imaging of the brain and cognitive testing evaluating. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry were performed. Pearson's correlation analysis was performed between these features of gray matter volume (GMV) and obstructive apnea index (OAI) among children with OSA. RESULTS: In the comparison of children's Wechsler test scores of full-scale intelligence quotient and verbal intelligence quotient, the OSA group was significantly lower than the control group (p < 0.05). Compared with the control group, the GMV of many brain regions in the OSA group was significantly decreased (p < 0.05). In the correlation analysis of GMV and OAI in OSA group, right inferior frontal gyrus volume was significantly negatively correlated with OAI (r = - 0.49, p = 0.02). CONCLUSION: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions. This finding suggests an association between the OSA and decreased GMV in children.

Amelioration of Cholesterol Rich diet-induced Impaired Cognition in AD Transgenic Mice by an LXR Agonist TO901317 Is Associated with the Activation of the LXR-ß-RXR-α-ABCA1 Transmembrane Transport System and Improving the Composition of Lipid Raft.

BACKGROUND: It has been reported that LXR agonist can inhibit Aß generation and alleviate Aß-induced various adverse reactions in vivo and in vitro experiments, but the mechanisms have not been clarified. The study aimed to observe the effect of LXR agonist TO901317 on the cognitive function of AD transgenic mice fed with cholesterol-rich diet (CRD), and to explore the possible mechanism. Methods: 32 male 6-month-old double transgenic AD mice were enrolled and randomly divided into 4 groups: control (normal diet) group, CRD treatment group, TO901317 treatment group and GSK2033 treatment group. After 3 month, Morris water maze was for the changes of spatial exploration and memory ability; ELISA was for detecting the production of Aß42 in the brain; the concentration of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) in serum were detected by cholesterol enzyme colorimetry; Finally, the expression of LXR-ß, RXR-α, ABCA1, caveolin-1, BACE1 and APP at protein level in the brains was measured by Western blotting. RESULTS: Compared with the control group, the learning, memory ability and spatial exploration ability of the mice were more significantly serious in the CRD group (P<0.05); The contents of TC and LDL in the serum and the production of Aß42 in the brains were significantly increased (P<0.05), but HDL was remarkably decreased (P<0.05); The protein levels of LXR-ß, RXR-α and ABCA1 were also significantly decreased (P<0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P<0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P<0.05); The contents of TC and LDL in serum and the production of Aß42 in the brains were significantly decreased (P<0.05), but HLD was increased (P<0.05); The protein levels of LXR-ß, RXR-α, ABCA1were all significantly increased (P<0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P<0.05). All the changes were reversed by GSK2033 (P<0.05). CONCLUSIONS: TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-ß/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aß42 in the brains.

Effects of Cerebellar Transcranial Direct Current Stimulation in Patients with Stroke: a Systematic Review.

BACKGROUND: The cerebellum is involved in regulating motor, affective, and cognitive processes. It is a promising target for transcranial direct current stimulation (tDCS) intervention in stroke. OBJECTIVES: To review the current evidence for cerebellar tDCS (ctDCS) in stroke, its problems, and its future directions. METHODS: We searched the Web of Science, MEDLINE, CINAHL, EMBASE, Cochrane Library, and PubMed databases. Eligible studies were identified after a systematic literature review of the effects of ctDCS in stroke patients. The changes in assessment scale scores and objective indicators after stimulation were reviewed. RESULTS: Eleven studies were included in the systematic review, comprising 169 stroke patients. Current evidence suggests that anode tDCS on the right cerebellar hemisphere does not appear to enhance language processing in stroke patients. Compared with the sham group, stroke patients showed a significant improvement in the verb generation task after cathodal ctDCS stimulation. However, with regard to naming, two studies came to the opposite conclusion. The contralesional anodal ctDCS is expected to improve standing balance but not motor learning in stroke patients. The bipolar bilateral ctDCS protocol to target dentate nuclei (PO10h and PO9h) had a positive effect on standing balance, goal-directed weight shifting, and postural control in stroke patients. CONCLUSIONS: ctDCS appears to improve poststroke language and motor dysfunction (particularly gait). However, the evidence for these results was insufficient, and the quality of the relevant studies was low. ctDCS stimulation parameters and individual factors of participants may affect the therapeutic effect of ctDCS. Researchers need to take a more regulated approach in the future to conduct studies with large sample sizes. Overall, ctDCS remains a promising stroke intervention technique that could be used in the future.

Expert consensus on comprehensive geriatric assessment clinic / 中华老年医学杂志

Comprehensive geriatric assessment clinic can identify geriatric syndrome as well as geriatric health problems, and provide comprehensive systematic diagnosis and treatment for older patients, which is conducive to reducing the number of outpatient visits and saving medical costs.However, the construction of comprehensive geriatric assessment clinic in China is just in the initial stage.There are no guiding opinions on the orientation, work content, work process, and quality management.Therefore, this consensus was conducted based on the latest evidence and expert opinions which aims to provide guidance for the construction of comprehensive geriatric assessment clinic.

Expert consensus on antiviral therapy of COVID-19 / 中华临床感染病杂志

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Value of SPECT myocardial perfusion imaging and coronary flow reserve combined with coronary artery calcium score in the diagnosis of obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To study the value of myocardial perfusion imaging (MPI) and coronary flow reserve (CFR) combined with coronary artery calcium score (CACS) in the diagnosis of obstructive coronary artery disease (CAD).Methods:From January 2019 to December 2020, 96 confirmed or suspective CAD patients (65 males, 31 females; age: 30-81 years) who completed rest/stress MPI, CFR and CACS defection in Fuwai Central China Cardiovascular Hospital were retrospectively analyzed. Coronary angiography (CAG) was used as the diagnostic standard to calculate the sensitivity and accuracy of MPI, CFR and MPI/CFR combined with CACS in the diagnosis of CAD. The χ2 test was used to compare the diagnostic efficiency of different methods. Results:The diagnostic sensitivity of MPI was 76.06%(54/71), and the accuracy was 75.00%(72/96), while the sensitivity increased to 97.18%(69/71; χ2=13.67, P<0.001) and the accuracy increased to 87.50%(84/96; χ2=4.92, P=0.020) with significant differences after combined with CACS. The sensitivity and accuracy of CFR were 91.55%(65/71)and 87.50%(84/96), which increased to 97.18%(69/71; χ2=2.12, P=0.137) and 89.58%(86/96; χ2=0.21, P=0.411) with no significant differences after combined with CACS. The sensitivity of MPI in the diagnosis of three-vessel CAD was 70.00%(21/30), which increased to 100%(30/30; χ2=7.75, P=0.004) after combined with CACS; while the sensitivity of MPI combined with CACS in the diagnosis of single-vessel and double-vessel CAD were not significantly improved ( χ2 values: 3.29, 1.51, P values: 0.114, 0.416). Conclusion:The combination of MPI and CACS can significantly improve the diagnostic efficiency of CAD, contributed by the improvement of the diagnostic sensitivity in three-vessel disease; whereas the diagnostic efficiency of CFR for CAD is not significantly improved after combined with CACS.

CEP33779 ameliorates pulmonary fibrosis associated with rheumatoid arthritis via the cross-talk between JAK2 and TGF-β 1 signaling pathway / 中华风湿病学杂志

Objective:Rat model of RA complicated with pulmonary fibrosis were constructed to observe the degree of improvement of pulmonary fibrosis in RA rats by JAK2 inhibitor CEP33779 and the possible mechanisms.Methods:①The RA models were constructed by subcutaneous injection of 0.2 ml (1 mg/ml) of bovine type Ⅱ collagen into the tail of the rats on the day of modeling development (d0); intratracheal injection of 100 μl bleomycin (2.5 mg/kg) was used to induce pulmonary fibrosis model at d13. In vivo study: model rats were randomly divided into the normal group, pulmonary fibrosis group, pulmonary fibrosis CEP treatment group, RA complicated with pulmonary fibrosis group, and RA complicated pulmonary fibrosis CEP treatment group. Rats in the treatment group was given CEP (10 ml/kg) qd by gavage from d14 to week 4. The right hind foot of the rats was measured for joints swelling and the arthritis index score were measured, lung compliance (Cst) and lung specific gravity were measured. In addition, the pathological changes of the left lung were observed by HE and Masson staining, and the extracellular matrix level of the right lung was measured by protein immunoblotting (WB). ② In vitro study: TGF-β 1 (10 ng/ml) was applied to stimulate human embryonic lung fibroblasts (HFL1) for 24 h and 48h, and p-JAK2 expression was detected by immunofluorescence. After HFL1 inoculation of culture plates, the control group, TGF-β 1 stimulation group, TGF-β 1+ LY2109761 (TGFβ-R1/2 inhibitor group, 0.5 mmol/L and 2 mmol/L) group, TGF-β 1+CEP (0.1 mmol/L and 1.0 mmol/L) group were co-incubated for 48 h, and the expression levels of TGFβ-R2, α-SMA, JAK2, and Col 1 were measured by WB. Comparisons between multiple groups were made by Tukey′s test, and comparisons between the two groups were analyzed by independent t-test. Results:① In vivo study, compared with the control group (1.45±0.04), joint swelling was increased at d13 [(2.54±0.16) in RA+PF+Vehicle group, t=16.02, P<0.001], and the mean arthritis index score and toe volume were decreased 3 days after CEP treatment(d16) [(2.89±0.11), t=5.78, P<0.001; (1.92±0.13), t=6.85, P<0.001]. For rats with pulmonary fibrosis, all had different degrees of lung enlargement, increased lung specific gravity, decreased Cst, and increased lung inflammation and fibrosis[(0.96±0.06), t=19.76, P<0.001; (0.26±0.09), t=17.64, P<0.001; (3.63±1.51), t=6.00, P<0.001; (1.75±0.71), t=5.84, P<0.001]. After CEP gavage, rats that had RA complicated with pulmonary fibrosis had reduced lung swelling, decreased lung specific gravity, increased Cst [(0.82±0.05), t=5.76, P<0.001; (0.43±0.18), t=2.31, P=0.038], and the scores of pulmonary fibrosis and inflammation [(3.00±1.00); (1.56±0.52)] all showed a trend of decrease, but did not reach statistical difference CEP inhibited the expression of TGF-β 1, TGFβ-R2, α-SMA, Fn and JAK2 in lung tissue of pulmonary fibrosis rats, and the differences among the five groups were statistically significant ( F=9.02, P=0.017; F=4.86, P=0.048; F=6.57, P=0.032; F=11.26, P=0.010; F=13.32, P=0.007). ② In vitro study, TGF-β 1 stimulated HFL1 showed stronger phosphorylated JAK2 (p-JAK2) fluorescent signal WB showed a significant increase in the expression of TGFβ-R2, α-SMA, JAK2 and Col1, and after LY and CEP intervention, the above proteins were reduced in a concentration-dependent manner, with statistically significant differences among all five groups ( F=337.30, P<0.001; F=20.61, P<0.001; F=100.60, P<0.001; F=180.90, P<0.001). Conclusion:JAK2 inhibitors can ameliorate RA-related pulmonary fibrosis, and the mechanism may be through interfering with the "crosstalk" between JAK2 and TGF-β 1 signaling pathway.

Evaluation of measuring vomer-palate diameters at 11-13 + 6 weeks of gestation and its diagnostic value for cleft lip and palate / 中华超声影像学杂志

Objective:To investigate the reference range of the length and thickness of the fetal vomer-palate diameters at 11-13 + 6 weeks, and their role in the diagnosis of cleft lip and palate(CLP). Methods:From May 2020 to August 2021, 1 559 pregnant women who underwent ultrasound examination at 11-13 + 6 weeks in Guangdong Women and Children Hospital were selected, and the fetal vomer-palate in the median sagittal plane of the face was observed. The length and thickness diameters of the fetal were measured separately to establish the reference value range of normal fetal.The reference range was compared with the vomer-palate data of fetuses with confirmed CLP. Results:The 1 518 normal fetuses were divided into 11-13 + 6 weeks, 12-12 + 6 weeks and 13-13 + 6 weeks. The reference values of the long diameter of fetal vomer-palatine were 4.3-5.9 mm, 5.0-6.8 mm, 5.4-7.7 mm, and the reference values of the thick diameter were 2.0-2.9 mm, 2.2-3.4 mm, and 2.5-3.8 mm, respectively. The length and thickness of the fetal vomer-palatine were significantly positively correlated with the Crown-rump length ( rs=0.733, 0.634; all P<0.001). In the 1 559 fetals, 25 cases were diagnosed and confirmed with CLP, and the vomer-palate thickness diameters were smaller than the reference values in all cases, meanwhile, the vomer-palate length diameters of 22(88.0)% cases were smaller than the reference values. Conclusions:The reference range of fetal vomer-palate length and thickness at 11-13 + 6 weeks of gestation is valuable for the screening of fetal CLP.

A calf tissue flap combined with antibiotic-loaded calcium sulfate for foot and ankle osteomyelitis / 中华创伤骨科杂志

Objective:To evaluate the efficacy of a calf tissue flap combined with antibiotic-loaded calcium sulfate (artificial bone or mixed iliac bone graft) in the treatment of foot and ankle osteomyelitis.Methods:A retrospective study was conducted to analyze the 11 cases of foot and ankle osteomyelitis which had been treated at Department of Hand and Microsurgery, The Third Hospital of Baoji from October 2018 to October 2021. There were 8 males and 3 females, aged (42.3±23.7) years. The chronic hypotoxic osteomyelitis was repaired and reconstructed after thorough debridement at one stage with a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone to fill the cavity and cover the wound. The acute infected trauma was repaired and reconstructed after thorough debridement at the second stage with a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone to fill the cavity and cover the wound only after the acute infection was controlled by local dressing, drainage or negative pressure therapy and systemic anti-infection treatment at the primary stage. The flap size ranged from 3.5 cm × 2.0 cm to 12.0 cm × 6.0 cm. Four cases were treated by a peroneal artery perforator flap combined with antibiotic-loaded calcium sulfate artificial bone, 3 cases by a flap with peroneal artery perforator and peroneal nerve trophic vessel combined with antibiotic-loaded calcium sulfate artificial bone, 3 cases by a posterior tibial artery perforator flap combined with antibiotic-loaded calcium sulfate artificial bone, and one by a peroneus longus muscle flap combined with antibiotic-loaded calcium sulfate artificial bone. Postoperatively, the flap survival, bone union time, ankle function and complications were observed; the therapeutic efficacy was evaluated by comparing infection control indexes at the final follow-up [clinical manifestations like local redness, swelling, pain, ulceration, and exudation, and white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and calcitoninogen (PCT)].Results:All the flaps survived except for one which developed necrosis at the distal 1/3 of the flap but responded to dressing change. All the patients were followed up for (22.6±11.5) months. The 6-month follow-up revealed that all the flaps were fine in shape and texture. Re-examinations showed that WBC, CRP, ESR and PCT were normal or close to normal, the local skin was free of redness, swelling or ulceration, and protective sensation was restored to varying degrees. X-ray at (12.1±2.3) months showed that lesions disappeared, bony union was achieved, the ankle joint regained basic flexion and extension, and the affected limb also regained weight-bearing and walking functions in all the patients but one whose X-ray at 18 months showed poor bony union but no other symptoms or signs.Conclusion:In the treatment of foot and ankle osteomyelitis, a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone can promote bone healing and restore the function of the foot and ankle because it not only fills the cavity and covers the wound but also effectively controls the infection.

The role of antibiotics in the treatment of Crohn′s disease / 中国医师杂志

Crohn′s disease (CD) is a chronic, progressive and destructive inflammatory disease affecting the entire digestive tract. Changes in the intestinal microbiota, particularly a decrease in gut microbiome diversity, are thought to be associated with chronic intestinal inflammation of CD. As for the mechanism of antibiotics in CD treatment, some scholars believe that antibiotics can affect the course of disease by reducing the concentration of intestinal bacteria and changing the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole and rifaximin, have been proved to have certain therapeutic effect on some patients with CD in clinical practice, but there are still limitations in the use of antibiotics.In this review, the relationship between intestinal flora and the incidence of CD and the application of antibiotics in CD were reviewed, providing reference and help for the standardized application of antibiotics in CD.

Effects of paliperidone palmitate long-acting injection on clinical symptoms and social function in patients with schizophrenia in communities / 中华行为医学与脑科学杂志

Objective:To understand the effects of paliperidone palmitate (PP) long-acting injection on hospitalization, psychiatric symptoms, individual and social function of community patients with schizophrenia.Methods:From March 2021 to September 2022, 239 patients with schizophrenia in the community of Zhongshan city were treated with PP injection in a 1-month dosage form for 1 year.The hospitalization rate was compared before and after the treatment.The brief psychiatric rating scale (BPRS), modified overt aggression scales(MOAS), clinical global impressions-severity(CGI-S), and personal and social performance scale (PSP) were used to evaluate psychiatric symptoms and personal social function at baseline, at the end of the 8th week, the end of the 6th month and the end of the 12th month after treatment.Repeated measurement analysis of variance was used to compare the results at different times of treatment, and Logistic regression analysis was used to analyze the factors affecting treatment by SPSS 26.0.Results:One year after treatment the number of hospitalization was lower than that before (0(1) times, 0(0) times)( Z=-4.43, P<0.01), and the hospitalization days was lower than before (43(83.3) days, 0(0) days)( Z=-8.65, P<0.01) for the schizophrenic patients.The total BPRS score for schizophrenic patients decreased from (45.3±9.2) to (27.5±9.0) after 1 year of treatment( χ2=465.20, P<0.01), and the external aggressive behavior score was lower than the baseline score (1(7), 0(0))( F=308.36, P<0.01). The total effective rates were 30.5%(73/239), 77.4%(185/239) and 81.6%(195/239) after 8 weeks, 6 months and 1 year of treatment, respectively.The impairment in the four aspects of personal and social functioning were improved to varying degrees (all P<0.01). The severity of the disease was reduced 1 year after treatment.And the proportions of partial to very severe, moderate, none or mild were 10.0%(24/239), 56.5%(135/239), and 33.5%(80/239). Ordinal logistic regression analysis showed that younger age at treatment ( β=-0.08, OR=0.93, 95% CI=0.87-0.99) and older age at first onset ( β=0.07, OR=1.07, 95% CI=1.01-1.14) were associated with better treatment outcomes. Conclusion:Long-term injection of paliperidone palmitate can effectively improve the mental symptoms and individual social function of community patients with schizophrenia.