AIM:To investigate the relationship between the expression of phosphatidylinositol 3-kinase cata-lytic subunit alpha(PIK3CA)gene in circulating tumor cells(CTCs)and the prognosis of colorectal cancer patients,and to construct a corresponding predictive model.METHODS:This retrospective study included 110 newly diagnosed and treated colorectal cancer patients at Guangzhou Red Cross Hospital from January 2019 to December 2021.Peripheral blood samples were collected and tested for CTC and PIK3CA gene at first visit.We determined the expression levels of PIK3CA gene in CTCs of different subtypes by typing and counting CTCs.Patients were randomly divided into training group(n=77)and validation group(n=33)in a ratio of 7∶3.Univariate and multivariate Cox regression analyses were per-formed to assess the associations between clinicopathological factors and patient prognosis.A nomogram model was con-structed to predict survival of patients at 6,12 and 24 months.The model performance was evaluated and validated using the concordance index(C-index),receiver operating characteristic(ROC)curve,and decision curve analysis(DCA)in the validation group.And then,the clinical application value of the model was further evaluated using the DCA curve.RESULTS:Univariate analysis showed that N1 and N2 stage,M stage(M1),carcinoembryonic antigen(CEA)level,liver metastasis,and lung metastasis were independent risk factors for prognosis(P<0.01).Multivariate analysis showed that age,gender,N1 stage,TNM stage(IIC,IIIA,IV),CEA level,liver metastasis,lung metastasis,and PIK3CA ex-pression in mixed CTCs were correlated with prognosis(P<0.05).The nomogram model based on PIK3CA expression demonstrated excellent predictive performance in the validation group,with areas under the ROC curve(AUC)of 0.952(6 months),0.931(12 months),and 0.957(24 months).The DCA curve showed that the model had a high net benefit across a wide range of decision thresholds.CONCLUSION:The different expression levels of PIK3CA gene in CTC are correlated with the survival rate of patients.Especially in mixed CTCs,high expression of PIK3CA gene is associated with shorter overall survival.The clinical prediction model nomogram has good clinical application value in predicting the sur-vival rate of colorectal cancer patients.The decision curve analysis also shows that the model has good net benefits and clinical application value.

Objective:To digitally measure the three-dimensional (3D) size of primary tooth crowns and the dimensions of the dental arch in children with individual normal primary dentition, preliminarily obtaining baseline data on the 3D size of primary tooth crowns as well as the length and width of the dental arch, and their influence factors. This study aims to provide a data foundation for the design of reference models for primary dentition.Methods:From May to June 2021, 122 caries-free children aged 3.5-4.5 years with individual normal occlusion were selected from five kindergartens in Haidian District, Beijing. Impressions were taken and plaster models were cast. After preliminary screening, 67 eligible models were scanned to obtain digital dental models. Digital measurement software was used for landmark-based measurements. Parameters included 3D crown dimensions (mesiodistal diameter, buccolingual diameter, and occlusogingival height), dental arch dimensions (length and width at specific regions), and occlusal measurements (overjet and overbite at the primary central incisors, and Bolton index for anterior and full dentition). Gender differences in crown dimensions and bilateral symmetry of homologous teeth, as well as the correlations between arch dimensions and gender, height, weight, and body mass index (BMI) were analyzed.Results:The homonymous teeth of 67 children exhibited strong bilateral symmetry in all 3D dimensions ( P>0.05). Gender differences were observed in the buccolingual dimension for all deciduous molars except for the right mandibular first deciduous molar ( P<0.05). For the occlusogingival dimension, gender differences were found in the right maxillary first and second deciduous molars, left maxillary first deciduous molar, and left mandibular first and second deciduous molars ( P<0.05). For the mesiodistal dimension, only the left mandibular second deciduous molar and right mandibular deciduous canine showed gender differences ( P<0.05). All significant differences above indicated larger dimensions in boys compared to girls. In both maxillary and mandibular arches, the lengths and widths at various locations were significantly larger in boys than in girls ( P<0.05). Univariate correlation analysis revealed that body weight was positively correlated with the width of the terminal plane in both the maxilla and mandible and the total length of the mandibular dental arch, while BMI was positively correlated with the width of the maxillary terminal plane and the widths at all measured sites in the mandible ( P<0.05). Multiple regression analysis demonstrated that, after controlling for relevant variables, BMI was a significant positive predictor for the lengths and widths at various sites of the dental arch ( P<0.05), and height was a positive predictor for dental arch length ( P<0.05), as well as body weight was a positive predictor for the width in the molar region ( P<0.05). Overjet at the primary central incisors was 2.28 (1.57, 2.66) mm, and overbite was 1.13 (0.75, 1.92) mm. The anterior Bolton index was 0.79±0.03, and the overall Bolton index was 0.94±0.03. Conclusions:Primary tooth crowns of individual normal occlusion children demonstrate strong bilateral symmetry in homologous teeth. Most primary molars exhibit gender differences in buccolingual and occlusogingival dimensions, with larger values in boys. Arch dimensions (length and width) are consistently larger in boys.

Objective:To digitally measure the three-dimensional (3D) size of primary tooth crowns and the dimensions of the dental arch in children with individual normal primary dentition, preliminarily obtaining baseline data on the 3D size of primary tooth crowns as well as the length and width of the dental arch, and their influence factors. This study aims to provide a data foundation for the design of reference models for primary dentition.Methods:From May to June 2021, 122 caries-free children aged 3.5-4.5 years with individual normal occlusion were selected from five kindergartens in Haidian District, Beijing. Impressions were taken and plaster models were cast. After preliminary screening, 67 eligible models were scanned to obtain digital dental models. Digital measurement software was used for landmark-based measurements. Parameters included 3D crown dimensions (mesiodistal diameter, buccolingual diameter, and occlusogingival height), dental arch dimensions (length and width at specific regions), and occlusal measurements (overjet and overbite at the primary central incisors, and Bolton index for anterior and full dentition). Gender differences in crown dimensions and bilateral symmetry of homologous teeth, as well as the correlations between arch dimensions and gender, height, weight, and body mass index (BMI) were analyzed.Results:The homonymous teeth of 67 children exhibited strong bilateral symmetry in all 3D dimensions ( P>0.05). Gender differences were observed in the buccolingual dimension for all deciduous molars except for the right mandibular first deciduous molar ( P<0.05). For the occlusogingival dimension, gender differences were found in the right maxillary first and second deciduous molars, left maxillary first deciduous molar, and left mandibular first and second deciduous molars ( P<0.05). For the mesiodistal dimension, only the left mandibular second deciduous molar and right mandibular deciduous canine showed gender differences ( P<0.05). All significant differences above indicated larger dimensions in boys compared to girls. In both maxillary and mandibular arches, the lengths and widths at various locations were significantly larger in boys than in girls ( P<0.05). Univariate correlation analysis revealed that body weight was positively correlated with the width of the terminal plane in both the maxilla and mandible and the total length of the mandibular dental arch, while BMI was positively correlated with the width of the maxillary terminal plane and the widths at all measured sites in the mandible ( P<0.05). Multiple regression analysis demonstrated that, after controlling for relevant variables, BMI was a significant positive predictor for the lengths and widths at various sites of the dental arch ( P<0.05), and height was a positive predictor for dental arch length ( P<0.05), as well as body weight was a positive predictor for the width in the molar region ( P<0.05). Overjet at the primary central incisors was 2.28 (1.57, 2.66) mm, and overbite was 1.13 (0.75, 1.92) mm. The anterior Bolton index was 0.79±0.03, and the overall Bolton index was 0.94±0.03. Conclusions:Primary tooth crowns of individual normal occlusion children demonstrate strong bilateral symmetry in homologous teeth. Most primary molars exhibit gender differences in buccolingual and occlusogingival dimensions, with larger values in boys. Arch dimensions (length and width) are consistently larger in boys.

AIM:To investigate the relationship between the expression of phosphatidylinositol 3-kinase cata-lytic subunit alpha(PIK3CA)gene in circulating tumor cells(CTCs)and the prognosis of colorectal cancer patients,and to construct a corresponding predictive model.METHODS:This retrospective study included 110 newly diagnosed and treated colorectal cancer patients at Guangzhou Red Cross Hospital from January 2019 to December 2021.Peripheral blood samples were collected and tested for CTC and PIK3CA gene at first visit.We determined the expression levels of PIK3CA gene in CTCs of different subtypes by typing and counting CTCs.Patients were randomly divided into training group(n=77)and validation group(n=33)in a ratio of 7∶3.Univariate and multivariate Cox regression analyses were per-formed to assess the associations between clinicopathological factors and patient prognosis.A nomogram model was con-structed to predict survival of patients at 6,12 and 24 months.The model performance was evaluated and validated using the concordance index(C-index),receiver operating characteristic(ROC)curve,and decision curve analysis(DCA)in the validation group.And then,the clinical application value of the model was further evaluated using the DCA curve.RESULTS:Univariate analysis showed that N1 and N2 stage,M stage(M1),carcinoembryonic antigen(CEA)level,liver metastasis,and lung metastasis were independent risk factors for prognosis(P<0.01).Multivariate analysis showed that age,gender,N1 stage,TNM stage(IIC,IIIA,IV),CEA level,liver metastasis,lung metastasis,and PIK3CA ex-pression in mixed CTCs were correlated with prognosis(P<0.05).The nomogram model based on PIK3CA expression demonstrated excellent predictive performance in the validation group,with areas under the ROC curve(AUC)of 0.952(6 months),0.931(12 months),and 0.957(24 months).The DCA curve showed that the model had a high net benefit across a wide range of decision thresholds.CONCLUSION:The different expression levels of PIK3CA gene in CTC are correlated with the survival rate of patients.Especially in mixed CTCs,high expression of PIK3CA gene is associated with shorter overall survival.The clinical prediction model nomogram has good clinical application value in predicting the sur-vival rate of colorectal cancer patients.The decision curve analysis also shows that the model has good net benefits and clinical application value.

Objective To estimate the disease burden of silicosis in China from 1990 to 2021 and analyze its changing trend using the data from the Global Burden of Disease Study 2021 (GBD 2021), and to provide evidence for the prevention and control of silicosis. Methods Data on the incidence, prevalence, morbidity and death, mortality and disability-adjusted life year (DALY) of silicosis in China were extracted from the GBD 2021 to analyze the disease burden and age distribution of silicosis. The average annual percentage change (AAPC) was calculated to reflect the temporal trend of various disease burden indicators from 1990 to 2021. The results were then compared with those of the global population. Results In China, prevalent cases of silicosis increased by 116.62% from 79 075 in 1990 to 171 291 in 2021; incident cases of silicosis increased by 75.75% from 13 315 in 1990 to 23 401 in 2021; deaths of silicosis increased by 30.76% from 4 837 in 1990 to 6 326 in 2021; DALYs of silicosis increased by 14.84% from 150,729.65 person-years in 1990 to 173 091.06 person-years in 2021. The age-standardized rate of prevalence, incidence, mortality, DALY, YLL, and YLD of silicosis in China all showed a downward trend. The AAPC (95% CI) was -0.42% (-0.56% ~ -0.29%), -1.02% (-1.16 %~ -0.88%), -2.16% (-2.49% ~ -1.83%), -2.24% (-2.63% ~ -1.84%), -2.45% (-2.76% ~ -2.14%), and -0.42% (-0.54% ~ -0.29%), respectively. From 1990 to 2021, the age-standardized indicators of silicosis in China were all higher than the global level, and the differences were statistically significant (all P <0.05). The proportion of silicosis incident cases in the total incident cases of pneumoconiosis in China increased from 68.49% in 1990 to 78.58% in 2021. Conclusion The age-standardized indicators of silicosis in China showed a downward trend from 1990 to 2021, but the number of prevalent cases, incident cases, and DALYs showed an increasing trend. The age-standardized incident rate of silicosis in China remains at a high level, suggesting that further efforts should be made to prevent and control silicosis.

Objective To calculate the absorbed dose of ⁹⁰Y TheraSphere in the pancreas and the surrounding sensitive organs after the administration in the treatment of pancreatic cancer through the establishment of an individual voxel model, and to provide technical support for the clinical application of ⁹⁰Y TheraSphere in the treatment of pancreatic cancer. Methods An individualized voxel model was constructed in Geant4 software based on the CT images of the patient. 12 monoenergetic electron specific absorption fractions (SAFs) in the range of 0.01 to 1 MeV were calculated and validated against the ICRP data. The model and method were used to calculate the absorbed doses in the target organs under uniform and nonuniform distribution of ⁹⁰Y microspheres in the pancreas. Results The relative errors between the SAF values calculated based on the individualized voxel model and the ICRP data after mass calibration were less than 3.89%. When ⁹⁰Y was uniformly distributed in the pancreas, the absorbed dose in the pancreas was 4.69 × 10⁻⁷ Gy/Bq; the absorbed doses in the liver, kidneys, and spleen were 6.15 × 10⁻¹², 6 × 10⁻¹², and 1.65 × 10⁻¹¹ Gy/Bq, respectively. When ⁹⁰Y was distributed within the tumor, the absorbed dose in the tumor was 6.69 × 10⁻⁶ Gy/Bq and the absorbed dose in normal pancreas was 5.72 × 10⁻⁸ Gy/Bq. The fitted relationship between tumor volume V and administered activity A at the prescribed dose of 120 Gy was quadratic, with relatively low activity required for concentrated administration in the center of the tumor. Conclusion The Monte Carlo dose calculation method based on individual voxel model accurately predicted the absorbed doses in the surrounding sensitive organs (liver, kidneys, and spleen) when ⁹⁰Y TheraSphere was used to treat pancreatic cancer. These results and the analysis of the factors affecting the drug delivery activity will provide data support for the clinical research of ⁹⁰Y TheraSphere in pancreatic cancer.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Objective To explore the mechanism of butylphthalide(NBP)in regulating microglia acti-vation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy af-ter carbon monoxide poisoning(DEACMP).Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized in-to three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegeta-ble oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-bind-ing adapter molecule 1(IBA1)was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA.Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency(P=0.001,P=0.029),reduced nerve cells(P=0.001,P=0.035),up-regulated expression of IBA1(P=0.001,P=0.042),increased mean fluorescence intensity of IBA1(P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α(TNF-α)(P=0.002,P=0.024),inter-leukin(IL)-6(P=0.001,P=0.015),and IL-1β(P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency(P=0.025),increased nerve cells(P=0.039),down-regulated expression of IBA1(P=0.035),decreased average fluorescence intensity of IBA1(P=0.031),and lowered levels of TNF-α(P=0.028),IL-6(P=0.037),and IL-1 β(P=0.034).Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cog-nitive dysfunction and brain tissue damage caused by DEACMP.

Objective:To research and design a negative pressure environment that can be applied in container type of biological isolation shelter,so as to meet the stable negative pressure environment and dynamic intelligent regulation of pressure difference in the container during multimodal transportation,especially under air freight conditions.Methods:The design specifications and research achievements of pressure differences of negative pressure isolation equipment for infectious diseases at home and abroad were comprehensively analyzed.And then,one kind of power-distributed ventilation system without air duct was designed to achieve.The preseted pressure redundancy,real-time monitoring of sensors and dynamic follow-up of pressure were used to realize stable and intelligent regulation of negative pressure within the container during air freight.Results:After testing,the pressure differences of each region of the"three regions and two channels"included clean region,buffer region,contamination region,medical staff passage and patient passage within container type of biological isolation shelter under the negative pressure environment could meet the preseted requirements.The values of pressure differences at the outside of room of clean region,the toilet of clean region,the toilet of clean region of the second dressing room of the buffer region,the contamination region of the first dressing room of the buffer region,the toilet of contamination region and the outside of the room of contamination region were respectively 34.2,38.8,-8.0,-31.7,-15.1 and-44.6.The conditions of the pressure differences within each region of container,which dynamically met the requirements of Biosafety Level-Ⅲ(BSL-3)laboratory,were tested through the sensors,and intelligent display and control equipment that deployed inside of container.Conclusion:The stable negative pressure environment and intelligent regulation for pressure difference in each region of the container can take container to have more high biosafety characteristics,which can effectively ensure the safe transportation of whole region for patients with severe infectious diseases,and the transport and treatment under air freight condition.