Objective:To verify the prognostic value of perineural invasion and lymphovascular tumor embolus for patients with gastric cancer undergoing gastrectomy and postoperative chemotherapy, and establish a prognostic prediction nomogram model.Methods:According to 7∶3 radio, 781 gastric cancer patients were randomly divided into training cohort and internal validation cohort. One hundred fifty patients were utilized as the external validation cohort. Univariate and multivariate analysis were performed to evaluate the prognostic value of perineural invasion and lymphovascular tumor embolus, and construct the dynamic nomogram. The concordance index (C-index), net reclassification index and integrated discrimination improvement index, receiver operating characteristic curve, calibration curves and decision curve analysis were used to evaluate the nomogram.Results:Perineural invasion ( HR=1.486, 95% CI: 1.150-1.919, P<0.01) and lymphovascular tumor embolus ( HR=1.321, 95% CI: 1.030-1.693, P<0.05) were independent prognostic risk factors for patients with gastric cancer after gastrectomy and postoperative chemotherapy. C-index (training cohort: 0.734, internal validation cohort: 0.755, external validation cohort: 0.715), net reclassification index (training cohort: 0.228 for 3-year and 0.213 for 5-year OS prediction; internal validation cohort: 0.211 for 3-year and 0.279 for 5-year OS prediction; external validation cohort: 0.220 for 3-year and 0.440 for 5-year OS prediction) and integrated discrimination improvement index (training cohort: 0.051 for 3-year and 0.041 for 5-year OS prediction; internal validation cohort: 0.027 for 3-year and 0.036 for 5-year OS prediction; external validation cohort: 0.063 for 3-year and 0.153 for 5-year OS prediction) indicated that the nomogram performed better than the traditional TNM staging system ( P<0.05). Conclusions:Perineural invasion and lymphovascular tumor embolus are independent prognostic risk factors of gastric cancer patients after postoperative chemotherapy. The novel dynamic nomogram model based on perineural invasion and lymphovascular tumor embolus provides better assistance in evaluating prognosis of gastric cancer patients.

Objective To explore the development of new formulations new pharmaceutical cocrystal by combining hot melt extrusion and 3D printing technologies.Methods The insoluble drug ibuprofen and nicotinamide were selected as model drugs,and hot melt extrusion was applied to extrude ibuprofen-nicotinamide cocrystal by regulating the processing temperature,screw speed and residence time,etc.Hot-stage polarized light microscopy,powder X-ray diffraction,differential scanning calorimetry,Fourier transform infrared spectroscopy,and Raman spectroscopy were used for characterization analysis.The process research was carried out by investigating properties such as eutectic particle size and distribution,angle of repose,and vibrational solidity density.On this basis,two 3D printing techniques,fused deposition molding and selective laser sintering type,were selected for pharmaceutical cocrystal loaded sheet printing.Results A new formulation of pharmaceutical cocrystal tablets loaded with ibuprofen-nicotinamide was successfully printed through the combined application of hot-melt extrusion and 3D printing technologies.Conclusions Combined process of hot melt extrusion and 3D printing technology in the field of developing new pharmaceutical cocrystal formulations,laying the material foundation and scientific support for the development of new pharmaceutical cocrystal formulations with personalized and programmable release on demand.

Objective To explore the development of new formulations new pharmaceutical cocrystal by combining hot melt extrusion and 3D printing technologies.Methods The insoluble drug ibuprofen and nicotinamide were selected as model drugs,and hot melt extrusion was applied to extrude ibuprofen-nicotinamide cocrystal by regulating the processing temperature,screw speed and residence time,etc.Hot-stage polarized light microscopy,powder X-ray diffraction,differential scanning calorimetry,Fourier transform infrared spectroscopy,and Raman spectroscopy were used for characterization analysis.The process research was carried out by investigating properties such as eutectic particle size and distribution,angle of repose,and vibrational solidity density.On this basis,two 3D printing techniques,fused deposition molding and selective laser sintering type,were selected for pharmaceutical cocrystal loaded sheet printing.Results A new formulation of pharmaceutical cocrystal tablets loaded with ibuprofen-nicotinamide was successfully printed through the combined application of hot-melt extrusion and 3D printing technologies.Conclusions Combined process of hot melt extrusion and 3D printing technology in the field of developing new pharmaceutical cocrystal formulations,laying the material foundation and scientific support for the development of new pharmaceutical cocrystal formulations with personalized and programmable release on demand.

The unique geography,climate,and natural conditions of plateaus pose significant challenges to the physical health and combat effectiveness of stationed troops.In high-altitude regions,maladaptation can lead to acute mountain sickness,such as high-altitude pulmonary edema and high-altitude cerebral edema.Previous studies have shown that gradual acclimatization is an effective strategy for preventing and mitigating altitude sickness.Additionally,non-pharmacological strategies such as intermittent hypoxia and pre-simulated altitude training have also been proven to effectively promote altitude acclimatization.Conventional acclimatization strategies take longer time and are not conducive to rapid deployment of military personnel.In this article,we review various acclimatization training for individuals entering high-altitude areas,in order to provide a reference for the research and application of scientific and efficient altitude acclimatization training strategies.

Objective:To establish a serum detection method of surface-enhanced Raman spectroscopy (SERS) combining with machine learning for early screening of colorectal cancer (CRC).Methods:Serum samples were collected from 150 CRC patients diagnosed at Jiangdu People′s Hospital, Affiliated to Yangzhou University, and also from 37 healthy subjects. Gold nanohexapod (AuNHs) arrays were prepared using an oil-water interface self-assembly method. A 5 μl serum sample was applied onto the AuNHs array. Scatheless and rapid detection for serum were performed using a Renishaw inVia Raman spectrometer at room temperature with a laser wavelength of 785 nm, exposure time of 10 s, and power of 5 mW. The raw SERS spectra were preprocessed using Savitzky-Golay smoothing, AsLS baseline correction, and Min-Max normalization with Origin 2019 software. Furthermore, the principal component analysis (PCA)-support vector machine (SVM) model was constructed using Python′s scikit-learn library. Leave-One-Out Cross-Validation (LOOCV) was used to evaluate the model′s accuracy, sensitivity, specificity, and area under the curve (AUC).Results:The AuNHs arrays exhibited uniform morphology. The relative standard deviation (RSD) of the SERS intensity at 1 080 cm -1 was 5.69%, and the RSD of the SERS intensity at 1 340 cm -1 was 6.20%. The limit of detection (LOD) of the AuNHs array was 9.42×10 -12 mol/L. The PCA-SVM model achieved an accuracy of 90.91% (170/187), sensitivity of 96.79% (181/187), specificity of 99.47% (186/187), and an AUC of 0.98. The most significant characteristic peaks distinguishing different CRC stages were at 747, 940, 1 000, 1 447, and 1 612 cm -1. Conclusion:The serum detection method based on SERS combined with machine learning can accurately screen CRC with higher accuracy, sensitivity, and specificity, demonstrating potential clinical application value.

Objective:To establish a serum detection method of surface-enhanced Raman spectroscopy (SERS) combining with machine learning for early screening of colorectal cancer (CRC).Methods:Serum samples were collected from 150 CRC patients diagnosed at Jiangdu People′s Hospital, Affiliated to Yangzhou University, and also from 37 healthy subjects. Gold nanohexapod (AuNHs) arrays were prepared using an oil-water interface self-assembly method. A 5 μl serum sample was applied onto the AuNHs array. Scatheless and rapid detection for serum were performed using a Renishaw inVia Raman spectrometer at room temperature with a laser wavelength of 785 nm, exposure time of 10 s, and power of 5 mW. The raw SERS spectra were preprocessed using Savitzky-Golay smoothing, AsLS baseline correction, and Min-Max normalization with Origin 2019 software. Furthermore, the principal component analysis (PCA)-support vector machine (SVM) model was constructed using Python′s scikit-learn library. Leave-One-Out Cross-Validation (LOOCV) was used to evaluate the model′s accuracy, sensitivity, specificity, and area under the curve (AUC).Results:The AuNHs arrays exhibited uniform morphology. The relative standard deviation (RSD) of the SERS intensity at 1 080 cm -1 was 5.69%, and the RSD of the SERS intensity at 1 340 cm -1 was 6.20%. The limit of detection (LOD) of the AuNHs array was 9.42×10 -12 mol/L. The PCA-SVM model achieved an accuracy of 90.91% (170/187), sensitivity of 96.79% (181/187), specificity of 99.47% (186/187), and an AUC of 0.98. The most significant characteristic peaks distinguishing different CRC stages were at 747, 940, 1 000, 1 447, and 1 612 cm -1. Conclusion:The serum detection method based on SERS combined with machine learning can accurately screen CRC with higher accuracy, sensitivity, and specificity, demonstrating potential clinical application value.

Objective:To verify the prognostic value of perineural invasion and lymphovascular tumor embolus for patients with gastric cancer undergoing gastrectomy and postoperative chemotherapy, and establish a prognostic prediction nomogram model.Methods:According to 7∶3 radio, 781 gastric cancer patients were randomly divided into training cohort and internal validation cohort. One hundred fifty patients were utilized as the external validation cohort. Univariate and multivariate analysis were performed to evaluate the prognostic value of perineural invasion and lymphovascular tumor embolus, and construct the dynamic nomogram. The concordance index (C-index), net reclassification index and integrated discrimination improvement index, receiver operating characteristic curve, calibration curves and decision curve analysis were used to evaluate the nomogram.Results:Perineural invasion ( HR=1.486, 95% CI: 1.150-1.919, P<0.01) and lymphovascular tumor embolus ( HR=1.321, 95% CI: 1.030-1.693, P<0.05) were independent prognostic risk factors for patients with gastric cancer after gastrectomy and postoperative chemotherapy. C-index (training cohort: 0.734, internal validation cohort: 0.755, external validation cohort: 0.715), net reclassification index (training cohort: 0.228 for 3-year and 0.213 for 5-year OS prediction; internal validation cohort: 0.211 for 3-year and 0.279 for 5-year OS prediction; external validation cohort: 0.220 for 3-year and 0.440 for 5-year OS prediction) and integrated discrimination improvement index (training cohort: 0.051 for 3-year and 0.041 for 5-year OS prediction; internal validation cohort: 0.027 for 3-year and 0.036 for 5-year OS prediction; external validation cohort: 0.063 for 3-year and 0.153 for 5-year OS prediction) indicated that the nomogram performed better than the traditional TNM staging system ( P<0.05). Conclusions:Perineural invasion and lymphovascular tumor embolus are independent prognostic risk factors of gastric cancer patients after postoperative chemotherapy. The novel dynamic nomogram model based on perineural invasion and lymphovascular tumor embolus provides better assistance in evaluating prognosis of gastric cancer patients.

Objective:To compare the clinical characteristics, diagnostic plans, and treatment strategies of patients with combined burn-blast injuries caused by liquid plastic and liquid metal foreign objects in the body.Methods:This study was a retrospective cohort study. From January 2009 to July 2019, 41 patients with combined burn-blast injuries caused by hot solution explosion who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Qingdao Hospital of Rehabilitation University. The following indexes of all patients were collected, including gender, age, total burn area, admission time after injury, site of combined burn-blast injuries, and type of foreign objects in the body. According to the type of foreign objects in the body, the patients were divided into liquid plastic group (30 cases) and liquid metal group (11 cases). The following indexes of the two groups of patients were collected, including the clinical characteristics (swelling in the injury site, pain, fever, abscess formation, depth of injury, activity of foreign objects, and difficulty in removing foreign objects), imaging examinations (ultrasound, computed radiography, computed tomography, and magnetic resonance imaging examinations), treatment (repair period and repair method), and incidence of complications during follow-up after discharge.Results:There were 33 males and 8 females among the patients, aged 18-65 years. The total burn area was 1% to 78% total body surface area, the admission time after injury was 2 h to 7 d, the combined burn-blast injuries mainly occurred in the limbs and trunk, and the foreign objects in the body were liquid plastics (polyethylene and acrylonitrile butadiene styrene) and liquid metals (liquid iron and aluminum). The proportions with swelling in the injury site, injury with depth to the bone, poor mobility of foreign objects, and difficulty in removing foreign objects in patients in liquid plastic group were significantly higher than those in liquid metal group ( P<0.05). The proportions of confirming foreign objects in the body through computed radiography and computed tomography examinations in patients in liquid metal group were 7/7 and 8/8, respectively, which were significantly higher than 1/5 and 3/20 in liquid plastic group ( P<0.05); the proportion of confirming foreign objects in the body through ultrasound examination in patients in liquid metal group was 11/11, which was similar to 24/26 ( P>0.05); the proportion of confirming foreign objects in the body through magnetic resonance imaging examination in patients in liquid metal group was 2/2, which was the same as 4/4 in liquid plastic group. The proportions of patients in liquid plastic group who underwent stage Ⅰ wound repair and direct suture were significantly lower than those in liquid metal group ( P<0.05), while the proportions of patients who underwent delayed wound repair, skin grafting, and flap grafting were significantly higher than those in liquid metal group ( P<0.05). There was no statistically significant difference in the incidence of complications between the two groups of patients during follow-up after discharge ( P>0.05). Conclusions:Combined burn-blast injuries could result in damages of different severity in patients due to different types and locations of foreign objects in the body. Computed radiography and computed tomography examinations can be used to diagnose metal foreign objects in the body, while ultrasound and magnetic resonance imaging examinations can be used to diagnose plastic foreign objects in the body. Multidisciplinary collaboration and comprehensive treatment are important means of treating this type of patients.

AIM:To elucidate the possible biological mechanism of silica-induced acute lung injury in rats.METHODS:Sixteen Male Sprague-Dawley rats were divided into control and acute silicosis model groups,and instilled intratracheally with 1 mL of normal saline and 50 g/L silica suspension,respectively.After 7 d,the rats were sacrificed for collection of lung tissue and serum.The serum levels of interleukin-1β(IL-1β),IL-18 and tumor necrosis factor-α(TNF-α)were measured by using ELISA.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and gasdermin D(GSDMD)were measured by immunohistochemistry.Bacterial DNA was ex-tracted from the lung tissue for 16S ribosomal RNA gene sequencing to characterize changes in the composition of lung flo-ra.The differences in the structure of bacterial flora between control and model groups were analyzed by bioinformatic analy-ses.RESULTS:Immunohistochemical analysis showed that the protein expression levels of NLRP3 and GSDMD were higher in the lungs of the rats in model group.In addition,serum cytokine profiling showed that IL-1β,IL-18 and TNF-α levels were significantly higher in model group.The most abundant bacterial genera in the lung flora of the rats in model group were Bifidobacterium,Clostridium sensu stricto 1,and Parasutterella.The NLRP3 and GSDMD levels in the lung tissue and IL-1β and TNF-α levels in serum were positively correlated with the abundance of Parasutterella.CONCLU-SION:The alterations in lung flora structure and increased inflammation levels may be the actual biological mechanisms underlying silica-induced acute lung injury.The modulation of lung flora may provide a basis for the prevention and treat-ment of silica-induced acute lung injury.

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.