Deep transcranial magnetic stimulation for schizophrenia: a systematic review.

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia. Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted. Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10). Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings.

Narrative Review and Consensus Recommendations for the Use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange in Modified Electroconvulsive Therapy.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a safe, effective, and novel technique that is currently being used in electroconvulsive therapy (ECT). This study aimed to summarize the clinical practices of THRIVE use in ECT to aid physicians and institutions in implementing the best practice guidelines for ECT. Thus, we reviewed the current literature and presented our consensus on the application of THRIVE in ECT in daily clinical practice. This consensus provides information regarding THRIVE use in ECT, including its safety, effectiveness, procedures, precautions, special case management, and application in special populations. Moreover, it guides the standardized use of THRIVE in ECT.

Deep transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis of randomized controlled studies.

The efficacy and safety of deep transcranial magnetic stimulation (dTMS) in treating treatment-resistant depression (TRD) are unknown. Up to June 21, 2023, we conducted a systematic search for RCTs, and then extracted and synthesized data using random effects models. Five RCTs involving 507 patients with TRD (243 in the active dTMS group and 264 in the control group) were included in the present study. The active dTMS group showed significantly higher study-defined response rate (45.3% versus 24.2%, n = 507, risk ratio [RR] = 1.87, 95% confidence interval [CI]: 1.21-2.91, I2 = 53%; P = 0.005) and study-defined remission rate (38.3% versus 14.4%, n = 507, RR = 2.37, 95%CI: 1.30-4.32, I2 = 58%; P = 0.005) and superiority in improving depressive symptoms (n = 507, standardized mean difference = -0.65, 95%CI: -1.11--0.18, I2 = 82%; P = 0.006) than the control group. In terms of cognitive functions, no significant differences were observed between the two groups. The two groups also showed similar rates of other adverse events and all-cause discontinuations (P > 0.05). dTMS is an effective and safe treatment strategy for the management of patients with TRD.

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review.

Objective: Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD). Methods: Randomized controlled trials (RCTs) comparing the efficacy and safety of iTBS and HF-rTMS were identified by searching English and Chinese databases. The primary outcomes were study-defined response and remission. Results: Two RCTs (n = 474) investigating the efficacy and safety of adjunctive iTBS (n = 239) versus HF-rTMS (n = 235) for adult patients with TRD met the inclusion criteria. Among the two included studies (Jadad score = 5), all were classified as high quality. No group differences were found regarding the overall rates of response (iTBS group: 48.0% versus HF-rTMS group: 45.5%) and remission (iTBS group: 30.0% versus HF-rTMS group: 25.2%; all Ps > 0.05). The rates of discontinuation and adverse events such as headache were similar between the two groups (all Ps > 0.05). Conclusion: The antidepressant effects and safety of iTBS and HF-rTMS appeared to be similar for patients with TRD, although additional RCTs with rigorous methodology are needed.

Electroconvulsive therapy knowledge and attitudes among patients and caregivers in South China: A preliminary study.

Background: Electroconvulsive therapy (ECT) is a safe and effective therapy for individuals suffering from major psychiatric disorders, but attitudes towards ECT among patients and caregivers have not been well studied. This study was conducted to elucidate patient and caregiver knowledge and attitudes concerning ECT in South China. Methods: The sample comprised 92 patients diagnosed with major psychiatric disorders and their caregivers (n = 92). Participants completed questionnaire measures of knowledge and attitudes related to ECT. Results: Information before ECT was inadequately provided to both caregivers and patients (55.4% versus 37.0%, p < 0.05). Caregivers reported receiving more adequate information about the therapeutic effects (50.0% versus 44.6%), side effects (67.4% versus 41.3%), and risks (55.4% versus 20.7%) of ECT when compared to patients (all p < 0.05). However, less than half of patients and caregivers believed that ECT was effective (43.5% versus 46.7%, p > 0.05), while more than half of them believed that ECT was beneficial (53.3% versus 71.7%, p < 0.05), and approximately half of them believed that ECT was safe (50.0% versus 51.1%, p > 0.05). A total of 32.6% of patients and 55.4% of caregivers (p < 0.05) reported that ECT was used only for critically ill patients. A total of 62.0% of patients experienced side effects, with memory impairment being the most commonly reported. Conclusion: Clinicians should develop a systematic health education program before ECT treatment and ensure that patients and caregivers have an accurate understanding of ECT, particularly the treatment process, its therapeutic effects and potential side effects prior to administering this treatment.

The osteoprotective effects and mechanisms of RA model mice by total saponins of Chaenomeles speciosa / 中国药房

OBJECTIVE To study the osteoprotective effects and possible mechanism of total saponins of Chaenomeles speciosa on rheumatoid arthritis （RA） model mice， and to provide reference for further development of anti-RA drugs. METHODS Seventy male DBA/1 mice were randomly divided into normal group， model group， low-dose and high-dose groups of C. speciose total saponins （60， 240 mg/kg）， Tripterygium wilfordii polyglycoside tablets group （positive control， 30 mg/kg）， with 14 mice in each group. In addition to the normal group， the other groups of mice were induced by glucose-6-phosphate isomerase mixed polypeptide to prepare RA model. The body weight， rear toes thickness and arthritis scores of each group were recorded； the synovial inflammation， bone and cartilage destruction of ankle joint tissues were observed by hematoxylin-eosin staining， tartrate- resistant acid phosphatase staining and safranin O-fast green staining； the contents of interleukin-6 （IL-6） in serum and tumor necrosis factor α （TNF-α）， IL-4 and IL-10 in ankle joint tissues were detected by ELISA； the expression levels of receptor activator of nuclear factor-κB ligand （RANKL）， receptor activator of nuclear factor-κB （RANK）， osteoprotegerin （OPG）， tumor necrosis factor receptor-associated protein 6 （TRAF6） and nuclear factor of activated T cells 1 （NFATC1） protein in ankle joint tissues were detected by Western blot assay. RESULTS At the end of administration， compared with normal group， the body mass of mice in the model group was significantly reduced （P＜0.05）， and the arthritis score and the thickness of the left and right rear toes were significantly increased （P＜0.05）； the ankle joint tissues of mice in the model group showed significant synovial proliferation and inflammatory infiltration， the number of osteoclasts increased significantly and significant destruction of cartilage tissue. The content of IL-6 in serum， the content of TNF-α， the protein expression levels of RANKL， RANK， TRAF6 and NFATC1 in the ankle joint tissues were increased significantly （P＜0.05）， while the contents of IL- 4 and IL-10， the protein expression level of OPG in the ankle joint tissues were decreased significantly （P＜0.05）. Compared with model group， above pathomorphological changes and the content/level of indicators of mice in each administration group were significantly improved （P＜0.05）. CONCLUSIONS Total saponins of C. speciosa may exert osteoprotective effects on RA model mice， the mechanism of which may be associated with reducing the contents of IL-6 and TNF-α， increasing the contents of IL-4 and IL-10， inhibiting the activation of RANKL/RANK/OPG signal pathway， thus inhibiting the proliferation of osteoclasts and promoting the repair of cartilage and bone tissue.

Research progress on the mechanism of Chinese medicine and active components against cartilage destruction of rheumatoid arthritis / 中国药房

Rheumatoid arthritis （RA） is a systemic chronic auto-inflammatory disease， characterized by infiltration of inflammatory cells， pannus formation， articular cartilage destruction， and bone matrix destruction. Therefore， improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components， multiple targets， high activity and low side effects. Based on this， the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors， phosphatidylinositol 3-kinase/protein kinase B， Wnt/β- catenin， nuclear factor-κB， mitogen-activated protein kinase， Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor， microRNAs， fibroblastic synovial cells.

Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification / 中国中药杂志

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

LOXL2 Inhibitor Attenuates Angiotensin II-Induced Atrial Fibrosis and Vulnerability to Atrial Fibrillation through Inhibition of Transforming Growth Factor Beta-1 Smad2/3 Pathway.

OBJECTIVES: Angiotensin II (Ang II)-induced atrial fibrosis plays a vital role in the development of atrial fibrillation (AF). Lysyl oxidase-like 2 (LOXL2) plays an essential role in matrix remodeling and fibrogenesis, indicating it may involve fibrosis-associated diseases. This study aims to elucidate the role of LOXL2 in AF, and its specific inhibitor can suppress Ang II-induced inflammatory atrial fibrosis and attenuate the enhanced vulnerability to AF. METHODS: Male mice C57BL/6 were subcutaneously infused with either saline or Ang II (2 mg/kg/day) for 4 weeks. DMSO or LOXL2 inhibitor LOXL2-IN-1 hydrochloride (LOXL2-IN-1) at a dose of 100 µg/kg/day were intraperitoneally injected once daily for 4 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced by transesophageal burst pacing in vivo. RESULTS: Expression of LOXL2 was increased in serum of AF patients and Ang II-treated mice. LOXL2-IN-1 significantly attenuated Ang II-induced AF vulnerability, cardiac hypertrophy, atrial inflammation, and fibrosis. LOXL2-IN-1 suppressed Ang II-induced expression of transforming growth factor beta-1 (TGF-ß1) and collagen I and phosphorylation of Smad2/3 in atrial tissue. CONCLUSIONS: LOXL2 is a target of AF, and its inhibitor prevents atrial fibrosis and attenuated enhanced vulnerability to AF potentially through the TGF-ß/Smad pathway.

Association of early serum potassium with all-cause mortality in adult maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To investigate the association of early serum potassium level with all-cause mortality in adult maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. The data of patients newly entered MHD in the registration system of Zhejiang province dialysis quality control center from January 1, 2010 to December 31, 2019 were collected. Follow-up was conducted until December 31, 2020. The average value of predialysis serum potassium within the first 3 months starting hemodialysis was defined as early serum potassium, and patients were divided into 6 groups according to their early serum potassium levels. Death within 1 year of MHD patients was defined as short-term death. Kaplan-Meier method was used to compare the long-term and short-term survival rates of the six groups. Cox regression model was used to analyze the association of different serum potassium levels with the short-term all-cause mortality of adult MHD patients.Results:A total of 27 362 patients aged (61.2±14.4) years old were included, including 16 775 males (61.3%), 1 303 patients (4.8%) with hypokalemia (serum potassium<3.5 mmol/L) and 10 034 patients (36.7%) with hyperkalemia (serum potassium≥5.0 mmol/L). Among them, there were 5 145 patients (18.8%) with serum potassium≥5.5 mmol/L. According to the early serum potassium levels, the patients were divided into group 1 (serum potassium<3.5 mmol/L), group 2 (3.5≤ serum potassium<4.0 mmol/L), group 3 (4.0≤serum potassium<4.5 mmol/L), group 4 (4.5≤serum potassium<5.0 mmol/L), group 5 (5.0≤serum potassium<5.5 mmol/L) and group 6 (serum potassium≥ 5.5 mmol/L), respectively. Until the end of follow-up, the follow-up time was (40.7±27.8) months and 5 400 patients died. Cardiovascular and cerebrovascular diseases [1 551 cases (28.7%)] and infections [366 cases (6.8%)] were the main causes of death. Kaplan-Meier survival analysis showed that the long-term and short-term cumulative survival rates in the serum potassium<3.5 mmol/L group were the lowest among the 6 groups (Log-rank test, χ2=119.0, P<0.001; χ2=74.6, P<0.001, respectively). Multivariate Cox regression analysis showed that early serum potassium<3.5 mmol/L was an independent influencing factor for short-term all-cause death in MHD patients (with 4.5≤serum potassium<5.0 mmol/L as reference, HR=1.54, 95% CI 1.26-1.89, P<0.001). In the subgroup of age≥65 years, multivariate Cox regression model showed that serum potassium<4.5 mmol/L was independently associated with short-term death in MHD patients (with 4.5≤ serum potassium< 5.0 mmol/L as reference, serum potassium<3.5 mmol/L, HR=2.16, 95% CI 1.69-2.75, P<0.001; 3.5≤serum potassium<4.0 mmol/L, HR=1.40, 95% CI 1.14-1.72, P=0.001; 4.0≤serum potassium< 4.5 mmol/L, HR=1.46, 95% CI 1.21-1.75, P<0.001), while in the subgroup of age<65 years, serum potassium level was not significantly associated with short-term mortality risk in MHD patients. The early serum potassium level was associated with the risk of short-term all-cause death in a "U" shape, and both low and high potassium levels increased the risk of short-term all-cause death. The optimal early blood potassium level was about 4.75 mmol/L. Conclusions:The prevalence of hypokalemia at early stage of dialysis in adult MHD patients is about 4.8%. There is a U-shaped association between early serum potassium level and short-term (1 year) all-cause mortality risk, and early serum potassium<3.5 mmol/L is an independent risk factor for long-term and short-term all-cause mortality in MHD patients.

Protective effect of heat shock transcription factor 1 on acute lung injury in septic rats by regulating NOD-like receptor protein 3 inflammasome activation / 中华危重病急救医学

Objective:To determine whether heat shock transcription factor 1 (HSF1) ameliorates sepsis induced acute lung injury (ALI) by regulating NOD-like receptor protein 3 (NLRP3) inflammasome activity in rat alveolar macrophages (AM).Methods:Twenty-four SPF Sprague-Dawley (SD) rats were divided into control group, lipopolysaccharide (LPS) group, overexpression empty vector+LPS group, and overexpression HSF1+LPS group by random number table method, with 6 rats in each group. The rat model of sepsis-induced ALI was reproduced by intraperitoneal injection of LPS (5 mg/kg); the rats in the control group were given the same volume of normal saline. The rats in the overexpression empty vector+LPS group and the overexpression HSF1+LPS group were instilled with 100 μL of overexpressed empty vector adenovirus or overexpressed HSF1 adenovirus through the trachea, respectively; the rats in the control group and LPS group were instilled with an equal volume of normal saline at the same time. At 6 hours after the model was reproduced, carotid blood was collected to determine the oxygenation index (PaO 2/FiO 2); lung tissue was obtained, and hematoxylin-eosin (HE) staining was performed to observe the pathological changes of lung tissue under a light microscope. Lung tissue wet/dry ratio (W/D) was determined. Immunohistochemistry was used to detect the positive expression of macrophage-specific marker antibody CD68. Western blotting was used to detect the protein expressions of HSF1 and NLRP3. Bronchoalveolar lavage fluid (BALF) was collected, and the levels of interleukins (IL-1β, IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). In addition, BALF of normal rats was collected, and primary AM was isolated, cultured and divided into four groups. The AM in the blank control group was cultured normally without any treatment; the LPS group was treated with 1 mg/L LPS for 24 hours to reproduced the LPS stimulation model; AM in the overexpression empty vector+LPS group and the overexpression HSF1+LPS group were transfected with empty vector plasmid or overexpressed HSF1 plasmid, respectively, for 48 hours, and then the AM was treated with 1 mg/L LPS. The cell viability was detected by cell counting kit-8 (CCK-8). The protein expressions of HSF1 and NLRP3 in AM were detected by Western blotting. The levels of IL-1β and IL-18 in AM culture medium were determined by ELISA. Results:Compared with the control group, the rat lung structure in the LPS group was severely injured, the alveolar cavity and pulmonary interstitium were congested and edema, the alveolar walls were significantly thickened and ruptured, accompanied by a large number of inflammatory cells infiltration. The lung W/D ratio increased, the infiltration degree of macrophages increased, PaO 2/FiO 2 decreased, HSF1 protein expression decreased and NLRP3 protein expression increased in lung tissue and AM, and IL-1β and IL-18 levels in BALF and AM culture medium increased. Compared with the LPS group, the degree of lung injury in the overexpression HSF1+LPS group was significantly improved, the lung W/D ratio was significantly reduced (4.76±0.16 vs. 6.93±0.33, P < 0.05), the macrophage infiltration was reduced, PaO 2/FiO 2 increased significantly [mmHg (1 mmHg≈0.133 kPa): 397.62±19.46 vs. 280.12±37.42, P < 0.05], HSF1 protein expression was significantly up-regulated in lung tissue and AM (HSF1/GAPDH: 0.90±0.04 vs. 0.61±0.04 in lung tissue, 1.10±0.10 vs. 0.57±0.08 in AM, both P < 0.05), NLRP3 protein expression was significantly down-regulated (NLRP3/GAPDH: 0.75±0.14 vs. 1.05±0.11 in lung tissue, 0.81±0.09 vs. 1.14±0.17 in AM, both P < 0.05), and the contents of IL-1β and IL-18 in BALF and AM medium were significantly decreased [IL-1β (ng/L): 7.82±0.45 vs. 14.09±0.58 in BALF, 11.11±0.46 vs. 16.66±0.96 in AM; IL-18 (ng/L): 50.44±3.30 vs. 66.31±5.67 in BALF, 43.95±0.88 vs. 73.52±1.23 in AM, all P < 0.05]. There was no significant difference in the detection indicators between the overexpression empty vector+LPS group and the LPS group. Conclusion:HSF1 attenuates LPS-induced ALI in rats, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation in AM.

Comparison of intracardiac and upturned approach for total anomalous pulmonary venous connection / 中华胸心血管外科杂志

Objective:Analyze the effect of intracardiac method and upturning method in the treatment of infracardiac total anomalous pulmonary venous connection(TAPVC), to explore the surgical method of infracardiac TAPVC.Methods:From July 2011 to August 2019, 20 patients with infracardiac TAPVC were treated, including 12 cases with upturning method and 8 cases with intracardiac method. The cardiopulmonary bypass time, aortic cross-clamp time, delayed thoracic closure, ICU time, mechanical ventilation time, postoperative days and anastomotic flow rate were compared between the two groups.Results:There was no significant difference in cardiopulmonary bypass time, aortic cross-clamp time, delayed thoracic closure, ICU time and mechanical ventilation time between the two groups. The postoperative hospital stay in upturning group was significantly lower than that in intracardiac group [(14.7±2.9)days vs.(16.1±6.2)days, P<0.05], and the postoperative anastomotic velocity > 120 cm/s in intracardiac group was significantly less than that in upturning group(1 case vs. 7 cases, P<0.05). Two patients died in upturning group, but there was no significant difference compared with the intracardiac group. Conclusion:There is no significant difference between the two methods in the treatment of subcardiac TAPVC. The authors think that the exposure of the upturning methods is difficult, and the distortion of the anastomosis may be hidden trouble. The in situ anastomosis of the intracardiac method is not easy to make mistakes.

Novel pectin from crude polysaccharide of Syzygium aromaticum against SARS-CoV-2 activities by targeting 3CLpro

To date, COVID-19 is still a severe threat to public health, hence specific effective therapeutic drugs development against SARS-CoV-2 is urgent needed. 3CLpro and PLpro and RdRp are the enzymes required for the SARS-CoV-2 RNA synthesis. Therefore, binding to the enzyme may interfere the enzyme function. Before, we found that sulfated polysaccharide binding to 3CLpro might block the virus replication. Hence, we hypothesize that negative charged pectin glycan may also impede the virus replication. Here we show that 922 crude polysaccharide from Syzygium aromaticum may near completely block SARS-CoV-2 replication. The inhibition rate was 99.9% (EC50 : 0.90 M). Interestingly, 922 can associates with 3CLpro, PLpro and RdRp. We further show that the homogeneous glycan 922211 from 922 may specifically attenuate 3CL protease activity. The IC50s of 922 and 922211 against 3CLpro are 4.73 {+/-} 1.05 {micro}M and 0.18 {+/-} 0.01 {micro}M, respectively. Monosaccharide composition analysis reveals that 922211 with molecular weight of 78.7 kDa is composed of rhamnose, galacturonic acid, galactose and arabinose in the molar ratio of 8.21 : 37.81 : 3.58 : 4.49. The structure characterization demonstrated that 922211 is a homogalacturonan linked to RG-I pectin polysaccharide. The linear homogalacturonan part in the backbone may be partly methyl esterified while RG-I type part bearing 1, 4-linked -GalpA, 1, 4-linked -GalpAOMe and 1, 2, 4-linked -Rhap. There are four branches attached to C-1 or C4 position of Rhamnose glycosyl residues on the backbone. The branches are composed of 1, 3-linked {beta}-Galp, terminal (T)-linked {beta}-Galp, 1, 5-linked -Araf, T-linked -Araf, 4-linked -GalpA and/or 4-linked {beta}-GalpA. The above results suggest that 922 and 922211 might be a potential novel leading compound for anti-SARS-CoV-2 new drug development.

Structural characterization of cocktail-like targeting polysaccharides from Ecklonia kurome Okam and their anti-SARS-CoV-2 activities in vitro

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the worldwide coronavirus disease 2019 (COVID-19) outbreak. Investigation has confirmed that polysaccharide heparan sulfate can bind to the spike protein and block SARS-CoV-2 infection. Theoretically, similar structure of nature polysaccharides may also have the impact on the virus. Indeed, some marine polysaccharide has been reported to inhibit SARS-Cov-2 infection in vitro, however the convinced targets and mechanism are still vague. By high throughput screening to target 3CLpro enzyme, a key enzyme that plays a pivotal role in the viral replication and transcription using nature polysaccharides library, we discover the mixture polysaccharide 375 from seaweed Ecklonia kurome Okam completely block 3Clpro enzymatic activity (IC50, 0.48 {micro}M). Further, the homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro molecule well (kD value : 4.23 x 10-6). Very interestingly, 37502 also can potently disturb spike protein binding to ACE2 receptor (EC50, 2.01 {micro}M). Importantly, polysaccharide 375 shows good anti-SARS-CoV-2 infection activity in cell culture with EC50 values of 27 nM (99.9% inhibiting rate at the concentration of 20 {micro}g/mL), low toxicity (LD50: 136 mg/Kg on mice). By DEAE ion-exchange chromatography, 37501, 37502 and 37503 polysaccharides are purified from native 375. Bioactivity test show that 37501 and 37503 may impede SARS-Cov-2 infection and virus replication, however their individual impact on the virus is significantly less that of 375. Surprisingly, polysaccharide 37502 has no inhibition effect on SARS-Cov-2. The structure study based on monosaccharide composition, methylation, NMR spectrum analysis suggest that 375 contains guluronic acid, mannuronic acid, mannose, rhamnose, glucouronic acid, galacturonic acid, glucose, galactose, xylose and fucose with ratio of 1.86 : 9.56 : 6.81 : 1.69 : 1.00 : 1.75 : 1.19 : 11.06 : 4.31 : 23.06. However, polysaccharide 37502 is an aginate which composed of mannuronic acid (89.3 %) and guluronic acid (10.7 %), with the molecular weight (Mw) of 27.9 kDa. These results imply that mixture polysaccharides 375 works better than the individual polysaccharide on SARS-Cov-2 may be the cocktail-like polysaccharide synergistic function through targeting multiple key molecules implicated in the virus infection and replication. The results also suggest that 375 may be a potential drug candidate against SARS-CoV-2.

Surgical experience of total anomalous pulmonary venous connection in adults / 中华胸心血管外科杂志

Objective:To explore the therapeutic strategy and result of adult total anomalous pulmonary venous connection(TAPVC).Methods:From November 2011 to November 2019, 6 adult patients with TAPVC underwent surgical correction. The Darling types include 4 cases of supracardiac , 1 case of intracardiac and 1 case of mixed type. There were 1 male and 5 female. The mean age was(28.6±4.8) years old and the mean weight was(47.3±3.67) kg. Preoperative oxygen saturation was 0.91±0.05.Results:All patients underwent primary repair successfully without perioperative death and complications. The average cardiopulmonary bypass time was(122.0±35.9) min, and the aortic cross-clamp time was(78.2±20.4) min. The mean postoperative hospitalization was(9.7±2.9) days, and the mean intensive care unit time was(3.5±1.4) days.The mean mechanical ventilation was(17.1±2.9) h. There were no later left heart dysfunction and pulmonary vein obstruction during the follow-up of 6-100 months.no pulmonary artery hypertension was identifed.Conclusion:TAPVC can be repaired savely in adult and satisfied result can be anticipated.

Comparative analysis of the treatment of partial anomalous pulmonary vein connection by double-patch method or Warden Technique / 中华胸心血管外科杂志

Objective:To compare the surgical and long-term follow-up results of partial anomalous pulmonary vein connection treated by double-patch method or Warden Technique.Methods:There were 33 cases of right pulmonary vein connected with the superior vena cava from May 2010 to May 2019 in our center treated by double-patch method or Warden technique. 21 cases were treated by double-patch method and 12 cases by Warden technique. Echocardiography and electrocardiogram were followed up regularly to observe the occurrence of arrhythmia, superior vena cava stenosis and pulmonary vein stenosis postoperatively.Results:All patients were discharged uneventfully, and were followed up for 1~8 years. In double-patch group, 2 cases with arrhythmia, 1 of whom was junctional arrhythmia which was automatically converted to sinus rhythm 1 day after surgery. The other had an early second degree atrioventricular block after surgery, and sinus rhythm was restored 3 days later with temporary pacemaker. 1 case had superior vena cava stenosis by echocardiography(PD 8 mmHg). No arrhythmia was found in long-term follow-up in Warden group. 2 cases had superior vena cava stenosis by echocardiography(PD 6 mmHg). Right pulmonary vein stenosis(PD 8 mmHg) was found in 1 case by echocardiography, no obvious aggravation was found in long-term follow-up.Conclusion:The double-patch method and Warden Technique are both safe and effective in the treatment of partial anomalous pulmonary venous connection.

Erythrocyte Sedimentation Rate in COVID-19 Infections

ObjectivesTo compare the clinical characteristics between the rapid cohort and the normal cohort of erythrocyte sedimentation rate (ESR) in COVID-19 infections, analyze the variables with significant differences, and explore the influencing factors of rapid ESR. MethodsSelected a total of 80 patients with ESR detection during hospitalization were measured in 146 patients who received medical observation in concentrated isolation hospital in Guizhou province in China, collected and compared demographic information, epidemiological data, clinical symptoms, laboratory test data and CT image data during the observation between rapid cohort and normal group of ESR. ResultsBy comparison, the proportion of male in the rapid cohort was higher than female. The average age was more than 35 years old, with a large age gap. The proportion of severe and critical patients was more than 26.53% (13/49). However, in the normal cohort the proportion of female was more than male, and the average age was about 8 years lower than the rapid cohort, and the age gap was smaller. The proportion of severe and critical patients was 12.90%, which was less than half of the rapid group. In the two groups, the proportion of clustered cases accounted for more than 50%, and the average number of patients in one family was more than 3. The most common clinical symptoms were cough, sputum, fever, sore throat and weakness of limbs. There were significant differences in ALT, {gamma}-GT and C-reactive protein between the rapid and normal cohort (P<0.05), but no statistically significant in other indicators. Hemoglobin and C-reactive protein have a significant effect on erythrocyte sedimentation rate. ConclusionsIn this study, we found that ESR is related to Hemoglobin and C-reactive protein. (Funded by Science and Technology Department of Guizhou Province; Chinese ClinicalTrials.gov number, ChiCTR2000033346. opens in new tab.)

Treatment of 6 COVID-19 Patients with Convalescent Plasma

ObjectiveTo describe the efficacy of convalescent plasma transfusion for COVID-19 patients. MethodsThis is a retrospective study of 6 COVID-19 patients with convalescent plasma at Guizhou Provincial Jiangjunshan Hospital - a tertial hospital, in Guiyang, Guizhou, China, from January 29, to April 30, 2020; final data of follow-up was May 12, 2020. Through the review of the electronic medical records of Guizhou Jiangjunshan Hospital, clinical data of 6 patients were obtained. Three patients with worsening symptoms after empirical treatment with antivirals were transfused convalescent plasma therapy for the first treatment, while the other three severe or critical COVID-19 patients with rapid progression were transfused. The efficacy of convalescent plasma depends on the relief of symptoms, changes in laboratory indicators and chest imaging abnormalities. ResultsThe PaO2 / FiO2 and lymphocyte count of patients 1, 2 and 3 treated with convalescent plasma treatment for the first treatment period were changed from abnormal to normal. The levels of inflammation markers CRP and IL-6 of the patients decreased significantly. Chest imaging examination showed that the lung lesions gradually subsided. The relapsed patients (No. 4 and No. 6), after using convalescent plasma therapy, turned negative on two consecutive throat swab tests on Day 24 and Day 3, respectively. ConclusionsConvalescent plasma treatment of COVID-19 is beneficial for those patients with be difficult to turn to negative or re-positive RT-PCR. Key PointsConvalescent plasma treatment of COVID-19 is beneficial for those patients with be difficult to turn to negative or re-positive RT-PCR.

Cordycepin inhibits pancreatic cancer cell growth in vitro and in vivo via targeting FGFR2 and blocking ERK signaling / 中国天然药物

Cordycepin (3'-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo. Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2 (checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2 (K = 7.77 × 10) very potently to inhibit pancreatic cancer cells growth by blocking Ras/ErK pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.

Gut-lymph-lung pathway mediates sepsis-induced acute lung injury / 中华医学杂志(英文版)

This review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of "gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome." Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.