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.

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.

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.

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.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia / 中华儿科杂志

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

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.

Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats. METHODS Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF- α， IL-6 and IL-1β， the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus （P＜0.05）； the escape latency time was shortened significantly （P＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （P＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （P＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （P＜0.05）. CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway， thus reducing hippocampal neuronal damage.

Predictive value of anticardiolipin antibody and D-dimer combined with risk assessment profile for thromboembolism for deep vein thrombosis in elderly postoperative patients with intertrochanteric fracture of femur / 中国医师进修杂志

Objective:To investigate the predictive value of anticardiolipin antibody (ACA) and D-dimer (D-D) combined with risk assessment profile for thromboembolism (RAPT) for deep vein thrombosis (DVT) in elderly postoperative patients with intertrochanteric fracture of femur (IFF).Methods:The clinical data of 123 elderly patients with IFF in Suzhou Hospital Affiliated to Anhui Medical University from January 2019 to March 2022 were retrospectively analyzed. All patients underwent closed reduction intramedullary nail fixation. The patients were divided into DVT group (27 cases) and non-DVT group (96 cases) according to the presence or absence of DVT 7 d after surgery. Before surgery and 3, 5 d after operation, the ACA was detected by enzyme-linked immunosorbent assay, the D-D was detected by automatic coagulation analyzer, and RAPT was performed. The correlation among ACA, D-D and RAPT was analyzed by Spearman method. Multivariate Logistic regression was used to analyze the independent risk factors of DVT in elderly postoperative patients with IFF. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of ACA, D-D and RAPT in predicting DVT in elderly postoperative patients with IFF. The incidences of postoperative DVT in patients with different ACA, D-D and RAPT patients were compared.Results:There were no statistical difference in ACA, D-D and RAPT before operation between the two groups ( P>0.05); the ACA, D-D and RAPT 3 and 5 d after operation in DVT group were significantly higher than those in the non-DVT group, 3 d after operation: (12.44 ± 3.25) × 10 3 RU/L vs. (8.67 ± 2.81) × 10 3 RU/L, (7.29 ± 1.49) mg/L vs. (4.70 ± 1.23) mg/L and (9.79 ± 1.15) scores vs. (9.21 ± 1.32) scores; 5 d after operation: (10.28 ± 2.16) × 10 3 RU/L vs. (6.45 ± 2.04) × 10 3 RU/L, (5.49 ± 1.26) mg/L vs. (3.63 ± 1.05) mg/L and (9.57 ± 1.08) scores vs. (9.12 ± 0.70) scores, and there were statistical differences ( P<0.01 or <0.05). Since ACA, D-D and RAPT in the two groups all reached their peak 3 d after operation, this time point was selected for analysis. Three days after operation, Pearson correlation analysis result showed that ACA and D-D were positively correlated with RAPT ( r = 0.635 and 0.630, P<0.01), and ACA was positively correlated with D-D ( r = 0.657, P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of ACA and D-D combined RAPT 3 d after operation in predicting DVT in elderly postoperative patients with IFF was greater than that predicted by the 3 indexes alone (0.982 vs. 0.894, 0.870 and 0.868), the optimal cut-off values were 11.48 × 10 3 RU/L, 6.75 mg/L and 9 scores. According to the optimal cut-off value of ROC curve analysis at 3 d after operation, the patients were divided into ACA low expression (≤11.48 × 10 3 RU/L, 92 cases) and ACA high expression (>11.48 × 10 3 RU/L, 31 cases), D-D low expression (≤6.75 mg/L, 99 cases) and D-D high expression (>6.75 mg/L, 24 cases), low RAPT (≤9 scores, 93 cases) and high RAPT (>9 scores, 30 cases). The incidences of postoperative DVT in patients with ACA high expression, D-D high expression and high RAPT were significantly higher than those in patients with ACA low expression, D-D low expression and low RAPT: 43.39% (15/31) vs. 13.04% (12/92), 54.17% (13/24) vs. 14.14% (14/99) and 53.33% (16/30) vs. 11.83% (11/93), and there were statistical differences ( χ2 = 16.91, 18.06 and 22.81; P<0.01). After controlling for diabetes and other factors, multivariate Logistic regression analysis result showed that ACA, D-D and RAPT 3 d after operation were independent risk factors for DVT in elderly postoperative patients with IFF ( OR = 2.156, 2.276 and 6.106; 95% CI 1.356 to 3.429, 1.240 to 4.177 and 1.564 to 23.840; P<0.01). Conclusions:The ACA, D-D combined with RAPT can improve the predictive value of DVT in elderly postoperative patients with IFF, which has important reference significance for taking timely and effective intervention measures in early clinical stage.

Research progress of perineural invasion in gallbladder cancer / 中华消化外科杂志

As a special mode of tumor metastasis, perineural invasion has been paid more and more attention. It is closely related to prognosis, recurrence and metastasis of tumor after surgery. As the most common malignancy of the biliary tract, perineural invasion is also an inde-pendent prognostic risk factor for gallbladder cancer due to its anatomical location, lymphatic reflux, blood perfusion and innervation. However, there are few studies on perineural invasion in gallbla-dder cancer, especially on its mechanism. By analyzing the general situation and recent progress of perineural invasion in gallbladder cancer, the authors mainly introduce the perineural invasion mechanism, perineural invasion rate of gallbladder cancer, relationship between perineural invasion and the clinical pathologic characteristic, the correlation with the prognosis, relationship with surgi-cal procedures and postoperative adjuvant therapy.

Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study / 中华消化外科杂志

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial / 中西医结合学报

BACKGROUND@#Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear.@*OBJECTIVE@#The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS@#We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment.@*MAIN OUTCOME MEASURES@#The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score.@*RESULTS@#The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant.@*CONCLUSION@#KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.