ABSTRACT
Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 μmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 μmol·L-1, respectively.
Subject(s)
Flavonoids/chemistry , SARS-CoV-2 , Rhizome , COVID-19 , Peptide Hydrolases , Antiviral Agents/chemistryABSTRACT
Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
Subject(s)
Humans , Male , Adult , Female , Xanthomatosis, Cerebrotendinous/pathology , Pedigree , Cholestanetriol 26-Monooxygenase/genetics , Mutation , AtaxiaABSTRACT
From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K (1-7), and six new 14-residue peptaibols, harzianins NPDG J-O (8-13). Additionally, four previously characterized 18-residue peptaibols neoatroviridins A-D (14-17) were also identified. The structural configurations of the newly identified peptaibols (1-13) were determined by comprehensive nuclear magnetic resonance (NMR) and high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) data. Their absolute configurations were further determined using Marfey's method. Notably, compounds 12 and 13 represent the first 14-residue peptaibols containing an acidic amino acid residue. In antimicrobial assessments, all 18-residue peptaibols (1-7, 14-17) exhibited moderate inhibitory activities against Staphylococcus aureus 209P, with minimum inhibitory concentration (MIC) values ranging from 8-32 μg·mL-1. Moreover, compound 9 exhibited moderate inhibitory effect on Candida albicans FIM709, with a MIC value of 16 μg·mL-1.
Subject(s)
Peptaibols/chemistry , Trichoderma/metabolism , Tandem Mass Spectrometry/methods , Anti-Infective Agents/pharmacology , Spectrometry, Mass, Electrospray Ionization/methodsABSTRACT
Objective To investigate the clinical data,brain pathology and molecular genetic characteristics of retinal vascular disease families with leukoencephalopathy and systemic damage.Methods The clinical data of two families of RVCL-S(retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations,RVCL-S)were collected and family maps were drawn to analyze the clinical manifestations,imaging,brain pathology and molecular genetic characteristics.Results Family 1:there were 3 male cases and the age of onset was 10 years,29 years and 40 years,respectively.Family 2:there was one male case and the age of onset was 32 years.Both families presented with retinal vascular disease,leukoencephalopathy and multi-system damage,the latter including liver,kidney and digestive tract involvement.There were 4 asymptomatic carriers in two families.The cranial CT of family 1-Ⅱ2 showed lamellar low density near the posterior corner of the left ventricle with multiple intracranial high density calcification.Brain MRI plain scan showed lateral ventricle lesions.The brain MRI plain and enhancement scans of family 1-I5 showed frontotemporal cortex lesions with peripheral edema and space occupying effect,and the ring enhancement was remarkable.The brain MRI plain scan and enhancement scan of family 2-Ⅱ1 showed the right and left frontal lobe lesions,accompanied by peripheral edema and enhancement,and the occupying effect was obvious.The operative pathology of brain tissue from family 1-I5 showed endothelial cell hyperplasia.The pathological manifestations of family 2-Ⅱ1 encephalopathy were consistent with"cerebral infarction"after two operations.The small blood vessels in the small intestinal wall showed endothelial cell proliferation.Molecular genetics:TREX1 D272Rfs heterozygous mutation was present in family 1-Ⅱ2,and his offspring including two daughters and one son were asymptomatic mutation carriers.TREX1 S246Ifs heterozygous mutation was detected in the 2-Ⅱ1 gene of the family which was not found in either the father or the mother found the mutation,and the son was asymptomatic carrier of the mutation.Conclusion The main clinical manifestations of RVCL-S are retinal vascular disease,nervous system involvement and multi-system damage.Imaging findings showed that intracranial lesions were space-occupying,accompanied by peripheral edema and enhancement.The pathological features were small vessel endothelial cell proliferation and lumen stenosis.Genetic results confirmed the presence of TREX1 gene mutation.
ABSTRACT
To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.
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Objective:To explore the safety and efficacy of the minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire and 3D-printed external template technique.Methods:A retrospective study was conducted of the clinical data of 21 patients with unstable pelvic fracture who had undergone minimally invasive treatment at Department of Orthopaedics, Union Hospital from May 2016 to July 2018 using 3D-printed external templates and the blunt head technique of Kirschner wire. There were 7 males and 14 females with an age of 43.6 years (from 19 to 65 years). According to the Tile classification, there were 3 cases of B1, 7 ones of B2, 6 ones of C1 and 5 ones of C2. The intraoperative fluoroscopy, operation time, postoperative fracture reduction and functional recovery of the pelvis at the last follow-up were recorded.Results:The 21 patients were followed up for an average of 16.3 months (from 12 to 24 months). A total of 33 wires were inserted in the 21 patients, including 15 S 1 ones and 18 S 2 ones. The intraoperative fluoroscopy ranged from 13 to 27 times, averaging 21.8 times. The operation time ranged from 65 to 130 min, averaging 88.6 min. The anterior subcutaneous internal fixation was used to fix the anterior ring in 9 patients. No vascular injury occurred during the operation. By the Matta criteria, the postoperative fracture reduction was assessed as excellent in 14 cases, good in 5, and fair in 2, giving an excellent to good rate of 90.5% (19/21). By the Majeed scoring system, the pelvic function at the last follow-up was assessed as excellent in 10 cases, good in 8, and fair in 3, giving an excellent to good rate of 85.7% (18/21). Lateral femoral cutaneous nerve injury occurred in 2 patients but was recovered by the 3-month follow-up. No other complications were follwed up. Conclusion:The minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire assissted by 3D-printed external templates is safe and effective, showing advatages of reduced fluoroscopic frequency and operation time.
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Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C
Subject(s)
Humans , Asteraceae , Circular Dichroism , Molecular Structure , SesquiterpenesABSTRACT
@#Objective To evaluate the safety and application value of three-dimensional reconstruction for localization of pulmonary nodules in thoracoscopic lung wedge resection. Methods The clinical data of 96 patients undergoing thoracoscopic lung wedge resection in our hospital from January 2019 to August 2020 were retrospectively reviewed and analyzed, including 30 males and 66 females with an average age of 57.62±12.13 years. The patients were divided into two groups, including a three-dimensional reconstruction guided group (n=45) and a CT guided Hook-wire group (n=51). The perioperative data of the two groups were compared. Results All operations were performed successfully. There was no statistically significant difference between the two groups in the failure rate of localization (4.44% vs. 5.88%, P=0.633), operation time [15 (12, 19) min vs. 15 (13, 17) min, P=0.956], blood loss [16 (10, 20) mL vs. 15 (10, 19) mL, P=0.348], chest tube placement time [2 (2, 2) d vs. 2 (2, 2) d, P=0.841], resection margin width [2 (2, 2) cm vs. 2 (2, 2) cm, P=0.272] or TNM stage (P=0.158). The complications of CT guided Hook-wire group included pneumothorax in 2 patients, hemothorax in 2 patients and dislodgement in 4 patients. There was no complication related to puncture localization in the three-dimensional reconstruction guided group. Conclusion Based on three-dimensional reconstruction, the pulmonary nodule is accurately located. The complication rate is low, and it has good clinical application value.
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Objective:To observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.Methods:From January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group ( n=27) and control group ( n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups. Results:The remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27) vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27) vs. 44.44% (12/27)], and there were statistically significant differences ( χ2=4.523, P=0.033; χ2=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/ml vs. (310.45±3.35) pg/ml, t=449.884, P<0.001; (135.68±1.60) pg/ml vs. (310.46±3.09) pg/ml, t=499.281, P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group ( t=-134.907, P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11% vs. 3.70%, χ2=0.270, P=0.603), neutropenia (14.81% vs. 11.11%, χ2<0.001, P>0.999), peripheral neuropathy (3.70% vs. 0, χ2<0.001, P>0.999), diarrhea (7.41% vs. 3.70%, χ2<0.001, P>0.999), nausea (3.70% vs. 0, χ2<0.001, P>0.999), epistaxis (7.41% vs. 0, χ2=0.519, P=0.471) or albuminuria (3.70% vs. 0, χ2<0.001, P>0.999) between the two groups. Conclusion:Intraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.