Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Background and objective The pathological types of lung ground glass nodules(GGNs)show great significance to the clinical treatment.This study was aimed to predict pathological types of GGNs based on computed tomog-raphy(CT)quantitative parameters.Methods 389 GGNs confirmed by postoperative pathology were selected,including 138 cases of precursor glandular lesions[atypical adenomatous hyperplasia(AAH)and adenocarcinoma in situ(AIS)],109 cases of microinvasive adenocarcinoma(MIA)and 142 cases of invasive adenocarcinoma(IAC).The morphological characteristics of nodules were evaluated subjectively by radiologist,as well as artificial intelligence(AI).Results In the subjective CT signs,the maximum diameter of nodule and the frequency of spiculation,lobulation and pleural traction increased from AAH+AIS,MIA to IAC.In the AI quantitative parameters,parameters related to size and CT value,proportion of solid component,energy and entropy increased from AAH+AIS,MIA to IAC.There was no significant difference between AI quantitative parameters and the subjective CT signs for distinguishing the pathological types of GGNs.Conclusion AI quantitative parameters were valu-able in distinguishing the pathological types of GGNs.

Objective To analyze the mutation of common driver genes in patients with non-small cell lung cancer(NSCLC)in eastern Henan Province.Methods A retrospective analysis was performed on 661 patients with NSCLC admitted to the First People's Hospital of Shangqiu city from March 2022 to July 2023.Five kinds of gene mutation detection kits(fluorescent PCR)were used for gene detection in all enrolled patients.The relationship between the clinical features and the status of each driver gene was analyzed by statistical methods.Results In the 661 patients with NSCLC,the mutation rates of EGFR,KRAS,ALK,ROS1,PIK3CA,BRAF,HER2,RET,MET14 and NRAS were 47.35%,9.68%,5.45%,1.82%,2.87%,1.82%,1.21%,0.91%,0.61%and 0%.Mutations in EGFR,ROS1 and HER2 were more likely to occur in women(P<0.05),while KRAS mutations were more common in men(P<0.05).The mutation rates of EGFR,KRAS and ALK in adenocarcinoma was significantly higher than that in squamous cell carcinoma and NSCLC.NOS(P<0.05),and the mutation rate of PIK3CA in NSCLC.NOS was the highest.The mutation rate of KRAS gene in stage Ⅰ+Ⅱ was significantly higher than that in stage Ⅲ+Ⅳ(P<0.05),and there was no significant correlation between other genes and clinical stage.Compared with smokers,the mutation rate of total driver gene was significantly higher in non-smokers(P<0.05).EGFR,ALK,PIK3CA,ROS1,BRAF and HER2 were more common in non-smokers(P<0.05),while KRAS gene was more common in smokers(P<0.05).The mutation rate of 10 driver genes in sediment cell block samples was 78.67%,and the detection rate was significantly higher than that in other types of samples(P<0.05).Conclusion Com-mon driver genes such as EGFR,KRAS and ALK are correlated with gender,pathological type,clinical stage and smoking.Qualified samples of sediment cells have obvious advantages for gene detection and could be widely pro-moted in patients.ARMS-PCR combined detection of 10 genes could be used as the preferred gene detection method for newly diagnosed and treated NSCLC patients.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P＜0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)

The syndrome/pattern of defensive qi deficiency is a common basic syndrome of traditional Chinese medicine in clinical practice. However,there is a lack of standardized and operable diagnostic specifications in practical applications. Based on the previous literature,this study proposed the idea of starting from the elements of the syndrome,qualitative diagnostic criteria for the syndrome/pattern of defensive qi deficiency oriented to the entire region of the disease were constructed based on the two dimensions of " deficient defensive qi failing to consolidate the exterior" and " qi deficiency" and constructing a set of quantitative evaluation criteria as the supporting content for the diagnostic items. The core members of the research group attempted to formulate the draft standard,then reached a consensus through the Delphi method expert questionnaire consultation and the Nominal group technique,and finally evaluated the reliability and validity of the standard through clinical verification to provide ideas for the standardization and normalization of research on syndromes.

Objective:To explore the role of arthroscopic exploration in the treatment of tibial plateau fractures with homeopathic double reverse traction reduction and internal fixation.Methods:A retrospective analysis was conducted on the data of 188 patients with tibial plateau fractures treated by homeopathic double reverse traction reduction assisted internal fixation and arthroscopic exploration at the Third Hospital of Hebei Medical University from January 2019 to December 2021. There were 129 males and 59 females, aged 46.7±11.8 years (range, 14-80 years); 115 cases on the left and 73 cases on the right. Schatzker classification of fractures: 81 cases of type II, 15 cases of type III, 23 cases of type IV, 29 cases of type V, and 40 cases of type VI. The time from injury to surgery was 1-14 days, with an average of 10±5 days. The surgery was performed with double reverse traction assisted reduction, locking bone plate and self-breaking compression bolt fixation. Then, arthroscopy was used to explore the quality of fracture reduction, meniscus and ligament damage, and the corresponding intra-articular lesions were treated, such as partial meniscus resection, complete meniscus resection, or suturing. The Rasmussen score was used to evaluate the quality of fracture reduction after surgery, and the Hospital for Special Surgery (HSS) knee joint score was used to evaluate the postoperative function of the knee joint.Results:All patients successfully completed fracture reduction, fixation, and arthroscopic exploration. The average surgical time was 95±21 min (range, 30-120 min); The average intraoperative bleeding volume was 120±58 ml (range, 50-300 ml). All patients were followed up for 10-24 months, with an average of 18±6.5 months. All patients' fractures achieved clinical healing after surgery, with a healing time of 2.5-6.0 months, with an average of 3±2.4 months. Among them, 165 patients (87.8%, 165/188) healed within 3 months after surgery, while the remaining 23 patients healed within 4-6 months after surgery. Arthroscopic exploration revealed that 188 patients had good fracture reduction and a flat articular surface. Among them, 97 cases (51.6%, 97/188) were complicated with meniscus injury, with longitudinal tear (29%, 28/97) being the most common, suture treatment was performed under arthroscopy; the remaining 69 patients underwent partial meniscectomy. All the patient's knee function recovered well at the last follow-up. 29 cases (15.4%, 29/188) were complicated with cruciate ligament injury, none of them underwent primary repair and were fixed with plaster or brace after operation. The Rasmussen score for the final follow-up after surgery was 16.8±2.4 points (range, 6-18 points), with 152 cases being excellent and 36 cases being good, with a 100% excellent and good rate. The HSS knee joint scores were 79.8±9.2 points, 85.1±10.1 points, and 94.9±7.6 points at 3, 6 months after surgery, and at the last follow-up, respectively, with statistically significant differences ( F=52.53, P<0.001). Superficial skin infection occurred in 2 cases after operation, which was cured by regular dressing change and anti-infection treatment with antibiotics. Deep vein thrombosis occurred in 7 cases within 1 week after operation, and low molecular weight heparin anticoagulation therapy was given. Conclusion:After using double reverse traction assisted reduction and internal fixation, arthroscopic examination can not only evaluate the quality of reduction for tibial plateau fractures, but also handle combined meniscus injuries and evaluate the condition of cruciate ligament injuries.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β‍‍-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.
Male ; Female ; Swine ; Animals ; Lipopolysaccharides/toxicity* ; Antioxidants/pharmacology* ; Rice Bran Oil ; Dysbiosis ; Dietary Supplements ; Diarrhea/veterinary* ; Weaning ; Body Weight