A simple and effective machine learning model for predicting the stability of intracranial aneurysms using CT angiography.

Background: It is vital to accurately and promptly distinguish unstable from stable intracranial aneurysms (IAs) to facilitate treatment optimization and avoid unnecessary treatment. The aim of this study is to develop a simple and effective predictive model for the clinical evaluation of the stability of IAs. Methods: In total, 1,053 patients with 1,239 IAs were randomly divided the dataset into training (70%) and internal validation (30%) datasets. One hundred and ninety seven patients with 229 IAs from another hospital were evaluated as an external validation dataset. The prediction models were developed using machine learning based on clinical information, manual parameters, and radiomic features. In addition, a simple model for predicting the stability of IAs was developed, and a nomogram was drawn for clinical use. Results: Fourteen machine learning models exhibited excellent classification performance. Logistic regression Model E (clinical information, manual parameters, and radiomic shape features) had the highest AUC of 0.963 (95% CI 0.943-0.980). Compared to manual parameters, radiomic features did not significantly improve the identification of unstable IAs. In the external validation dataset, the simplified model demonstrated excellent performance (AUC = 0.950) using only five manual parameters. Conclusion: Machine learning models have excellent potential in the classification of unstable IAs. The manual parameters from CTA images are sufficient for developing a simple and effective model for identifying unstable IAs.

Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen.

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.

Synthesis and pharmacological activity of vinpocetine derivatives.

Vinpocetine and its derivatives were extensively employed in the treatment of ischemic stroke, serving as effective cerebrovascular vasodilators. They could also be utilized for neuroprotection, anti-inflammatory purposes, anti-aging interventions, insomnia treatment, and antidepressant effects. However, due to issues such as hepatic first-pass effect, low bioavailability, and poor patient compliance with multiple dosing, the secondary development of Vinpocetine to address these limitations became a prominent area of research. Five primary methodologies were employed for the synthesis of Vinpocetine derivatives. These included substitution on the A ring to modify the 14-ester group, alteration of the 16-ethyl group, simplification of the D and E rings, and modification of the conformation of Vinpocetine. This paper summarized the current synthesis and activity studies of Vinpocetine and its derivatives, with the aim of providing a reference for the discovery of more potent derivatives of Vinpocetine.

Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

Multiphase MRI-Based Radiomics for Predicting Histological Grade of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer. Accurate preoperative prediction of histological grade holds potential for improving clinical management and disease prognostication. PURPOSE: To evaluate the performance of a radiomics signature based on multiphase MRI in assessing histological grade in solitary HCC. STUDY TYPE: Retrospective. SUBJECTS: A total of 405 patients with histopathologically confirmed solitary HCC and with liver gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month of surgery. FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted spoiled gradient echo sequence (LAVA) at 1.5 or 3.0 T. ASSESSMENT: Tumors were graded (low/high) according to results of histopathology. Basic clinical characteristics (including age, gender, serum alpha-fetoprotein (AFP) level, history of hepatitis B, and cirrhosis) were collected and tumor size measured. Radiomics features were extracted from Gd-EOB-DTPA-enhanced MRI data. Three feature selection strategies were employed sequentially to identify the optimal features: SelectFromModel (SFM), SelectPercentile (SP), and recursive feature elimination with cross-validation (RFECV). Probabilities of five single-phase radiomics-based models were averaged to generate a radiomics signature. A combined model was built by combining the radiomics signature and clinical predictors. STATISTICAL TESTS: Pearson χ2 test/Fisher exact test, Wilcoxon rank sum test, interclass correlation coefficient (ICC), univariable/multivariable logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), DeLong test, calibration curve, Brier score, decision curve, Kaplan-Meier curve, and log-rank test. A P-value <0.05 was considered statistically significant. RESULTS: High-grade HCCs were present in 33.8% of cases. AFP levels (odds ratio [OR] 1.89) and tumor size (>5 cm; OR 2.33) were significantly associated with HCC grade. The combined model had excellent performance in assessing HCC grade in the test dataset (AUC: 0.801), and demonstrated satisfactory calibration and clinical utility. DATA CONCLUSION: A model that combined a radiomics signature derived from preoperative multiphase Gd-EOB-DTPA-enhanced MRI and clinical predictors showed good performance in assessing HCC grade. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

Radiomic Analysis Based on Gd-EOB-DTPA Enhanced MRI for the Preoperative Prediction of Ki-67 Expression in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a random forest model based on radiomic features in Gd-EOB-DTPA enhanced MRI for predicting the Ki-67 expression in solitary HCC. MATERIALS AND METHODS: This retrospective study analyzed 258 patients with solitary HCC. Significant clinicoradiological factors were identified through univariate and multivariate analyses for distinguishing HCC with high (>20%) and low (≤20%) Ki-67 expression. Radiomic features were extracted at Gd-EOB-DTPA enhanced MRI. The recursive feature elimination (RFE) strategy was employed to screen robust radiomic features, and the Random Forest (RF) algorithm was utilized to rank radiomic features and construct prediction models. The AUC, accuracy, precision, recall, and f1-score were used to evaluate the performance of RF models. RESULTS: Multivariate analysis identified serum AFP level, tumor size, growth type, and peritumoral enhancement as independent predictors for HCC with high Ki-67 expression. The clinicoradiological-radiomic model that incorporated the clinicoradiological predictors and the top ten radiomic features outperformed the clinicoradiological model in the training set (AUCs 0.876 vs. 0.780; p < 0.001), though the test set did not have a statistical significance (AUCs 0.809 vs. 0.723; p = 0.123). The addition of clinicoradiological predictors did not yield a significant improvement in the performance of radiomic features in both sets (training, p = 0.692; test, p = 0.229). Decision curve analysis further confirmed the clinical utility of the RF models. CONCLUSION: The RF models based on radiomic features of Gd-EOB-DTPA enhanced MRI achieved satisfactory performance in preoperatively predicting Ki-67 expression in HCC.

Synthesis and Antiviral and Antitumor Activities of Novel 18ß-Glycyrrhetinic Acid Derivatives.

A series of novel derivatives of 18ß-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics.

Complete lumbarization with calcified disc herniations at L5S1 and S1-2 levels treated with percutaneous endoscopic interlaminar discectomy: a case report and technique note.

Objective: This study aims to report a case of a patient with complete lumbarization (Castellvi-IB) who developed symptomatic calcified disc herniations at L5S1 and lumbarized S1-2 levels and achieved excellent neurological recovery following percutaneous endoscopic interlaminar discectomy (PEID). Summary of Background Data: In 1984, Castellvi et al. classified lumbosacral transitional vertebra (LSTV) into four types. They incorrectly classified I LSTV anomalies as only type I sacralization, not realizing type I lumbarization also belonged to type I LSTV, with the latter exhibiting a well-developed S1-2 disc (lumbosacral transitional disc, LSTD). Patients with type I lumbarization rarely develop calcified disc herniations concomitantly at L5S1 and LSTD levels. PEID has been developed to perform discectomy for neurological decompression at the lumbar region, especially at the lowest level where the higher iliac crest and/or widened transverse process exists. Methods: A 47-year-old male presented to our hospital complaining of an intractable left leg radiating pain for 3 weeks after suffering from chronic radiating pain for 4 years. His physical examination found hyperalgesia at the lateral side of the left calf, decreased dorsal flexion strength of the ankle (grade 4/5), and a positive sign of straight leg raising test at the left side (30°). The preoperational Lumbar JOA (Japanese Orthopaedic Association) score was 12. Image examinations including whole spinal radiograph, MRI, and CT confirmed complete lumbarization (Castellvi-IB) with calcified disc herniations at L5S1 and LSTD levels at the left side. PEID was carried out at two index levels to accomplish decompression via the left approach. Results: The patient's neurological function recovered quickly. One day postoperatively, he began to walk without discomfort. After 3 months, his muscle strength recovered to normal, and after 6 months, the residual dysesthesia at his posterolateral calf disappeared. The follow-up Lumbar JOA score was 26. Conclusion: Calcified lumbar disc herniation could develop at two distal levels concomitantly in the case of type I complete lumbarization. This anomaly might be misinterpreted as a normal lumbar sequence by only lumbar MRI. PEID may be an effective procedure to treat such calcified disc herniations in a single visit.

Different effects of vaccine on VST in critical and non-critical COVID-19 patients: A retrospective study of 363 cases.

Aim: To explore the risk factors of prolonged viral shedding time (VST) in critical/non-critical COVID-19 patients during hospitalization. Methods: In this retrospective study, we enrolled 363 patients with SARS-CoV-2 infection admitted in a designated hospital during the COVID-19 outbreak in Nanjing Lukou International Airport. Patients were divided into critical (n = 54) and non-critical (n = 309) groups. We analyzed the relationship between the VST and demographics, clinical characteristics, medications, and vaccination histories, respectively. Results: The median duration of VST was 24 d (IQR, 20-29) of all patients. The VST of critical cases was longer than non-critical cases (27 d, IQR, 22.0-30.0 vs. 23 d, IQR 20-28, P < 0.05). Cox proportional hazards model showed that ALT (HR = 1.610, 95%CI 1.186-2.184, P = 0.002) and EO% (HR = 1.276, 95%CI 1.042-1.563, P = 0.018) were independent factors of prolonged VST in total cases; HGB (HR = 0.343, 95%CI 0.162-0.728, P = 0.005) and ALP (HR = 0.358, 95%CI 0.133-0.968, P = 0.043) were independent factors of prolonged VST in critical cases, while EO% (HR = 1.251, 95%CI 1.015-1.541, P = 0.036) was the independent factor of prolonged VST in non-critical cases. Vaccinated critical cases showed higher levels of SARS-CoV-2-IgG (1.725 S/CO, IQR 0.3975-28.7925 vs 0.07 S/CO, IQR 0.05-0.16, P < 0.001) and longer VSTs (32.5 d, IQR 20.0-35.25 vs 23 d, IQR 18.0-30.0, P = 0.011) compared with unvaccinated critical patients. Fully vaccinated non-critical cases, however, presented higher levels of SARS-CoV-2-IgG (8.09 S/CO, IQR 1.6975-55.7825 vs 0.13 S/CO IQR 0.06-0.41, P < 0.001) and shorter VSTs (21 d, IQR 19.0-28.0 vs 24 d, IQR 21.0-28.5, P = 0.013) compared with unvaccinated non-critical patients. Conclusions: Our results suggested that risk factors of prolonged VST were different between critical and non-critical COVID-19 patients. Increased level of SARS-CoV-2-IgG and vaccination did not shorten the VST and hospital stay in critical COVID-19 patients.

A modified percutaneous transforaminal endoscopic surgery for central calcified thoracic disc herniation at the T11/T12 level using foraminoplasty and decompression: A case report.

Background: Thoracic disc herniation (TDH) is uncommon. Central calcified TDH (CCTDH) is even rare. Traditional open surgery was considered a gold standard to treat CCTDH, but it was accompanied by a high risk of complications. Recently, a technique called percutaneous transforaminal endoscopic decompression (PTED) was adopted to treat TDH. Gu et al. designed a simplified PTED technique and named it percutaneous transforaminal endoscopic surgery (PTES) to treat various types of lumbar disc herniation; it offered the advantages of simple orientation, easy puncture, reduced steps, and little x-ray exposure. However, PTES to treat CCTDH has not been reported in the literature. Methods: Here, we describe the case of a patient with CCTDH treated with a modified PTES through the unilateral posterolateral approach under local anesthesia and conscious sedation by using a flexible power diamond drill. First, we report that the patient was treated with PTES with later-stage endoscopic foraminoplasty, with an inside-out technique employed at the initial endoscopic decompression stage. Results: A 50-year-old male with progressive gait disturbance and bilateral leg rigidity with paresis and numbness was diagnosed with CCTDH at the T11/T12 level on MRI and CT examinations. A modified PTES was performed on November 22, 2019. The total mJOA (modified Japanese Orthopedic Association) score preoperatively was 12. The method of the determination of incision and the soft tissue trajectory establishment process were the same as those in the original PTES technique. The foraminoplasty process was divided into initial fluoroscopic and final endoscopic stages. At the fluoroscopic stage, the hand trephine's saw teeth were just rotated into the lateral portion of the ventral bone from the superior articular process (SAP) to seize the SAP firmly, while at the endoscopic stage, in order to remove the ventral bone from the SAP safely under direct endoscopic visualization, adequate foramen enlargement was achieved without causing any risk of damage to the neural structures in the spinal canal. During the endoscopic decompression process, the soft disc fragments ventral to the calcified shell were undermined to form a cavity using an inside-out technique. Then, a flexible endoscopic diamond burr was introduced to degrade the calcified shell, and a curved dissector or a flexible radiofrequency probe was used to dissect the thin bony shell from the dural sac. Eventually, the shell was fractured within the cavity piece by piece to remove the whole CCTDH and achieve adequate dural sac decompression, resulting in minimal blood loss and no complications. The symptoms were gradually alleviated and the patient almost completely recovered at the 3-month follow-up, with no symptom recurrence found at the 2-year follow-up. The mJOA score improved to 17 at the 3-month follow-up and to 18 at the 2-year follow-up compared with 12 points preoperatively. Conclusions: A modified PTES may be an alternative minimally invasive technique for the treatment of CCTDH and provide similar or better outcomes over traditional open surgery. However, this procedure requires good endoscopic experience on the part of the surgeon and is beset with technical challenges and therefore should be performed with utmost care.

Endophytic Colletotrichum (Sordariomycetes, Glomerellaceae) species associated with Citrusgrandis cv. "Tomentosa" in China.

Colletotrichum species are well-known plant pathogens, saprobes, endophytes, human pathogens and entomopathogens. However, little is known about Colletotrichum as endophytes of plants and cultivars including Citrusgrandis cv. "Tomentosa". In the present study, 12 endophytic Colletotrichum isolates were obtained from this host in Huazhou, Guangdong Province (China) in 2019. Based on morphology and combined multigene phylogeny [nuclear ribosomal internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (gapdh), chitin synthase 1 (chs-1), histone H3 (his3) actin (act), beta-tubulin (ß-tubulin) and glutamine synthetase (gs)], six Colletotrichum species were identified, including two new species, namely Colletotrichumguangdongense and C.tomentosae. Colletotrichumasianum, C.plurivorum, C.siamense and C.tainanense are identified as being the first reports on C.grandis cv. "Tomentosa" worldwide. This study is the first comprehensive study on endophytic Colletotrichum species on C.grandis cv. "Tomentosa" in China.

Percutaneous Transforaminal Endoscopic Diskectomy for Lumbar Disk Herniation: Young (Age <60 years) versus Older (Age ≥60 years) Patients.

BACKGROUND: We compare the differences in the efficacy of percutaneous transforaminal endoscopic diskectomy (PTED) between the younger (age <60 years) and older (age ≥60 years) patients with lumbar disk herniation (LDH). METHODS: From December 2016 to December 2017, 128 patients with symptomatic LDH underwent PTED and were followed up. Forty-four 60 years old and above, including 19 males and 25 females with an average age of 68.7 (61-82) years, were classified as the elderly age group. Eighty-four patients younger than 60 years were classified as the young age group, which included 48 males and 36 females with an average age of 44.7 (16-58) years. The visual analog scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, and satisfaction rates of the two groups before and after surgery were compared. RESULTS: The operation was completed successfully in both groups. The average follow-up times of the elderly and young age groups were 18.47 ± 2.62 (12-23) and 17.90 ± 3.27 (12-23) months, respectively. One patient in the young age group had recurrence 7 months after surgery, and the symptoms were relieved after PTED was performed again. Two patients with nerve root injury after surgery in the young age group completely recovered after 2 months of conservative treatment. There were no significant surgical complications in the elderly age group. There was no significant difference in postoperative VAS, JOA, and MacNab scores between the two groups. The MacNab scores in the elderly age group were excellent for 28 patients, good for 10 patients, and fair for 6 patients; the satisfaction rate was 86.3%. In the young age group, scores were excellent for 63 patients, good for 14 patients, fair for 5 patients, and poor for 2 patients; the satisfaction rate was 91.7%. CONCLUSION: The clinical effectiveness of PTED for treatment of LDH in both elderly and young patients is satisfactory. Age is not a predictor of poor outcomes of PTED.

Synthesis and Activity Evaluation of Vinpocetine-Derived Indole Alkaloids.

This study focuses on the synthesis of novel vinpocetine derivatives (2-25) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as 1H NMR, 13C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3, 4, 5, 12, 14, 21, and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4, with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC50 value of 3.53 ± 0.25 µM. Additionally, compound 25, with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC50 = 2.08 ± 0.16 µM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π-π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand-protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development.

Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: A retrospective study of 25207 cases in a Fangcang hospital.

Objectives: To summarize the clinical characteristics of patients infected by SARS-CoV-2 omicron variant and explore the risk factors affecting the progression in a Fangcang hospital, Shanghai, China. Methods: A total of 25,207 patients were retrospectively enrolled. We described the clinical characteristics and performed univariate and multivariate logistic regression analysis to identify the risk factors for non-severe to severe COVID-19 or death. Results: According to the outcomes, there were 39 severe patients (including 1 death) and 25,168 non-severe patients enrolled in this study. Among the 25,207 cases, the median age was 45 years (IQR 33-54), and 65% patients were male. Cough (44.5%) and expectoration (38.4%) were the most two common symptoms. Hypertension (10.4%) and diabetes (3.5%) were most two common comorbidities. Most patients (81.1%) were fully vaccinated. The unvaccinated and partially vaccinated patients were 15.1% and 3.9%, respectively. The length of viral shedding time was six days (IQR 4-9) in non-severe patients. Multivariate logistic regression analysis suggested that age (OR=1.062, 95%CI 1.034-1.090, p<0.001), fever (OR=2.603, 95%CI 1.061-6.384, p=0.037), cough (OR=0.276, 95%CI 0.119-0.637, p=0.003), fatigue (OR=4.677, 95%CI 1.976-11.068, p<0.001), taste disorders (OR=14.917, 95%CI 1.884-118.095, p=0.010), and comorbidity (OR=2.134, 95%CI 1.059-4.302, p=0.034) were predictive factors for deterioration of SARS-CoV-2 omicron variant infection. Conclusions: Non-critical patients have different clinical characteristics from critical patients. Age, fever, cough, fatigue, taste disorders, and comorbidity are predictors for the deterioration of SARS-CoV-2 omicron variant infection.

Network pharmacology and molecular docking study on the effect of Kaempferol in treatment of metabolic associated fatty liver disease.

OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease (MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the SwissTargetPrediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the GeneCards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction (PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol; In cell experiment, oleic acid induced steatosis in HepG2 cells, which was intervened by kaempferol, the level of triglyceride (TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot. RESULTS: The results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B (PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B (AKT1), pros-taglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation. CONCLUSIONS: This study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD.

The Dolenc technique was used to clip 14 cases of ruptured basilar apex aneurysms and posterior cerebral artery aneurysms.

Objective: To investigate the surgical techniques and their clinical effects for ruptured basilar artery apex and posterior cerebral aneurysms via the Dolenc approach. Methods: We retrospectively analyzed the clinical data of 14 patients with ruptured basilar artery apex and posterior cerebral aneurysms who underwent surgical clipping by the Dolenc approach from July 2017 to June 2020 in Beijing Tiantan Hospital affiliated with Capital Medical University and Lianyungang Hospital affiliated with Xuzhou Medical University. The modified Rankin scale (mRs) scores were used to evaluate the prognosis of patients. Results: All 14 cases of aneurysms were successfully clipped. Overall, 1, 2, and 1 cases of postoperative new-onset visual loss, oculomotor nerve palsy, and contralateral hemiplegia, respectively, were reported. Digital subtraction angiography (DSA) or computed tomography angiography (CTA) examination of the aneurysm within 2 weeks after surgery revealed that the aneurysm was completely clipped without residue. The observations during the follow-up within 12-18 months after surgery were as follows: 1 case of vision loss returned to normal, 2 cases of oculomotor nerve palsy, 1 case of return to normal, 1 case of improved, 1 case of contralateral hemiplegia improved after rehabilitation treatment, and 1 case of hydrocephalus ventriculoperitoneal shunt surgery was performed. Overall, 11, 2, and 1 case had mRs scores of 0, 1, and 2, respectively. No death was reported. Conclusion: For the small number of basilar apical and posterior cerebral aneurysms treated non-invasively, the Dolenc approach may offer advantages over other modalities.

Correlation of CT-derived pectoralis muscle status and COVID-19 induced lung injury in elderly patients.

OBJECTIVES: To explore the association between CT-derived pectoralis muscle index (PMI) and COVID-19 induced lung injury. METHODS: We enrolled 116 elderly COVID-19 patients linked to the COVID-19 outbreak in Nanjing Lukou international airport. We extracted three sessions of their CT data, including one upon admission (T1), one during the first 2 weeks when lung injury peaked (T2) and one on day 14 ± 2 (T3). Lung injury was assessed by CT severity score (CTSS) and pulmonary opacity score (POS). Pneumonia evolution was evaluated by changes of CT scores at T2 from T1(Δ). RESULTS: The maximum CT scores in low PMI patients were higher than those of normal PMI patients, including CTSS1 (7, IQR 6-10 vs. 5, IQR 3-6, p < 0.001), CTSS2 (8, IQR 7-11 vs. 5, IQR 4-7, p < 0.001) and POS (2, IQR 1-2.5 vs. 1, IQR 1-2, p < 0.001). Comorbidity (OR = 6.15, p = 0.023) and the presence of low PMI (OR = 5.43, p = 0.001) were predictors of lung injury aggravation with ΔCTSS1 > 4. The presence of low PMI (OR = 5.98, p < 0.001) was the predictor of lung injury aggravation with ΔCTSS2 > 4. Meanwhile, presence of low PMI (OR = 2.82, p = 0.042) and incrementally increasing D-dimer (OR = 0.088, p = 0.024) were predictors of lung injury aggravation with ΔPOS = 2. CONCLUSIONS: PMI can be easily assessed on chest CT images and can potentially be used as one of the markers to predict the severity of lung injury in elderly COVID-19 patients.

Chromium toxicity induced oxidative damage in two rice cultivars and its mitigation through external supplementation of brassinosteroids and spermine.

The chromium (Cr) induced phytotoxicity avowed the scientific community to develop stress mitigation strategies to restrain the Cr accumulation inside the food chain. Whereas, brassinosteroids (BRs), and spermine (SPM) are well-known growth-promoting phytohormones, which enhance the plants health, and resilient the toxic effects under stress conditions. Until now, their interactive role against Cr-mitigation is poorly known. Hence, we conducted the hydroponic experiment to perceive the behavior of seed primed with BRs, or/and SPM treatment against Cr disclosure in two different rice cultivars (CY927; sensitive, YLY689; tolerant). Our findings delineated that BRs (0.01 µM), or/and SPM (0.01 mM) remarkably alleviated Cr-induced phytotoxicity by improving the seed germination ratio, chlorophyll pigments, PSII system, total soluble sugar, and minimizing the MDA contents level, ROS extra generation, and electrolyte leakage through restricting the Cr accretion in roots, and shoots of both rice cultivars under Cr stress. Additionally, the BRs, or/and SPM modulated the antioxidant enzyme, and non-enzyme activities to reduce the Cr-induced cellular oxidative damage as well as maintained the ionic hemostasis in both rice cultivars, especially in YLY689. Concisely, enhanced the plants biomass and growth. Overall, our outcomes revealed that BRs and SPM interact positively to alleviate the Cr-induced damages in rice seedlings on the above-mentioned indices, and combine treatment is much more efficient than solely. Moreover, the effect of BRs, or/and SPM was more obvious in YLY689 than CY927 to hamper the oxidative stress, and boost the antioxidant capacity.

Efficacy and safety of traditional Chinese medicine in patients with acute exacerbation of idiopathic pulmonary fibrosis: study protocol for randomized, controlled, exploratory clinical trial.

BACKGROUND: At present, there is short of effective treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The treatment of IPF with traditional Chinese medicine (TCM) has some advantages. However, the evidence is unclear whether TCM can be recommended as an effective therapy to treat AE-IPF. The purpose of the study is to explore the efficacy and safety of TCM for patients with AE-IPF. METHODS: A randomized, double-blind, placebo-controlled, exploratory clinical trial will be performed. A total of 80 patients diagnosed with AE-IPF will be randomized into the intervention or control group. In addition to conventional treatment, the intervention group will be treated with Kangxianhuanji granule, and the control group will be given a placebo granule. The administration frequency is 10 g each time and two times daily. After 4 weeks of treatment, the patients were followed up for 12 weeks. The primary outcomes are treatment failure rate and all-cause mortality. Secondary outcome measures will include the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, Modified British Medical Research Council (mMRC) score, the St George's Respiratory Questionnaire idiopathic pulmonary fibrosis (SGRQ-I) score, and arterial blood gas analysis. DISCUSSION: TCM may be beneficial in IPF. However, it has never been evaluated in patients with AE-IPF, who are incredibly prone to respiratory failure and have a high mortality rate. It is the first clinical trial to explore the efficacy and safety of TCM in the treatment of AE-IPF. This result will provide a basis for further study, which provides a high-quality evidence for the treatment of AE-IPF with TCM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026289 . Registered on 29 September 2019.

Characterization of Bacterial Community Structure Dynamics in a Rat Burn Wound Model Using 16S rRNA Gene Sequencing.

Burns destroy the skin barrier and alter the resident bacterial community, thereby facilitating bacterial infection. To treat a wound infection, it is necessary to understand the changes in the wound bacterial community structure. However, traditional bacterial cultures allow the identification of only readily growing or purposely cultured bacterial species and lack the capacity to detect changes in the bacterial community. In this study, 16S rRNA gene sequencing was used to detect alterations in the bacterial community structure in deep partial-thickness burn wounds on the back of Sprague-Dawley rats. These results were then compared with those obtained from the bacterial culture. Bacterial samples were collected prior to wounding and 1, 7, 14, and 21 days after wounding. The 16S rRNA gene sequence analysis showed that the number of resident bacterial species decreased after the burn. Both resident bacterial richness and diversity, which were significantly reduced after the burn, recovered following wound healing. The dominant resident strains also changed, but the inhibition of bacterial community structure was in a nonvolatile equilibrium state, even in the early stage after healing. Furthermore, the correlation between wound and environmental bacteria increased with the occurrence of burns. Hence, the 16S rRNA gene sequence analysis reflected the bacterial condition of the wounds better than the bacterial culture. 16S rRNA sequencing in the Sprague-Dawley rat burn model can provide more information for the prevention and treatment of burn infections in clinical settings and promote further development in this field.