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.

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.

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.

Objective To rapidly evaluate the efficacy,safety,and economics of dexmedetomidine in patients on mechanical ventilation in intensive care unit(ICU),and to provide references for clinical and decision makers.Methods To search PubMed,Embase,Cochrane Library,CNKI,WanFang Data databases and official websites of domestic and foreign Health Technology assessment(HTA)institutions from the inception to June 14,2023.HTA reports,systematic reviews/Meta-analyses,and pharmacoeconomic studies of patients with mechanical ventilation in ICU compared with dexmedetomidine versus placebo or other traditional sedatives were included.Two reviewers independently identified studies,extracted data,assessed the quality of included studies,and descriptive analyzed and summarised the results.Results A total of 13 literatures were included,including 10 systematic reviews/Meta-analyses and 3 economic studies.The analysis results of effectiveness showed that compared with placebo or other traditional sedatives,the use of dexmedetomidine in the sedation of mechanically ventilated patients in the ICU was associated with a shorter duration of mechanical ventilation and a shorter length of stay in the ICU.The analysis results of safety displayed treatment with dexmedetomidine could reduce the incidence of delirium,but may increase the incidence of bradycardia.The results of the economic analysis showed that the dexmedetomidine group had a higher cost of medication,but a lower overall ICU cost.Conclusion Dexmedetomidine has good efficacy,safety and economics in the sedation of patients on mechanical ventilation in ICU,but the economic studies included in the search were mainly foreign studies,and domestic economy studies needs to be further demonstrated.

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 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.

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.

Danggui Liuhuangtang is the 47^th of the 100 famous classical formulas published by the National Administration of Traditional Chinese Medicine， and is known as the holy medicine for night sweat. By bibliometrics， the authors collected the ancient books on Danggui Liuhuangtang and screened out 269 valid data， involving 156 ancient books of traditional Chinese medicine. The analysis on the historical origin， disease syndromes， pathogenesis， composition， dosage， preparation， usage， and processing of Danggui Liuhuangtang found that this famous classical formula originated from Secret Book of the Orchid Chamber （《兰室秘藏》） written by LI Dongyuan， and is composed of Angelicae Sinensis Radix， Rehmanniae Radix， Rehmanniae Radix Praeparata， Phellodendri Chinensis Cortex， Scutellariae Radix， Coptidis Rhizoma and Astragali Radix. It has the functions of nourishing Yin， reducing fire， consolidating exterior and stopping sweating， and mainly treats night sweat due to Yin deficiency and fire exuberance. In the later generations， disease syndromes are mostly treated based on LI Dongyuan's theory， and have expanded to more than 30 kinds （339 in total）， among which night sweat （208） was the most， accounting for 61.36% of the total disease syndromes， followed by spontaneous sweating （38）， accounting for 11.21%. Additionally， it was found that Danggui Liuhuangtang was widely used in modern clinical practice for various disease syndromes. Among them， endocrine disease （77， 28.21%） was predominant， followed by gynecological disease （48， 17.58%）， and pediatric disease （24， 8.79%）. Although Danggui Liuhuangtang treats many disease syndromes， their pathogenesis was always yin deficiency and fire exuberance. Through the systematic excavation of the ancient books on Danggui Liuhuangtang and the analysis of its modern clinical application， this paper probed into the historical evolution and confirmed the key information of the formula， providing detailed literature basis for the research and development application of famous classical formulas.

Objective An epidemiological investigation was carried out on the first family cluster epidemic of psittacosis in Wuhan to provide scientific basis for the prevention and control of Chlamydia psittacosis. Methods Epidemiological data were collected by field epidemiological investigation methods, and pathogenic testing was carried out by collecting cases, suspected exposed persons, and environmental samples. Results The 2 cases in the same family stared with fever, headache and chills. The first case was treated in 5 medical institutions and hospitalized in 2 of them. The results of metagenomic next-generation sequencing in the bronchoalveolar lavage fluid of the case indicated that it was infected with Chlamydia psittaci. Thirty environmental samples from cases and 3 pigeon farmers homes, 4 throat swabs from family members of pigeon farmers were collected, and 15 environmental samples were positive by real-time fluorescence quantitative polymerase chain reaction, all of which were in the cases' home and neighbor farmers' homes, including 8 pigeon feces smearing samples, 3 pigeon drinking residual water samples, 1 sand and corn eaten by pigeons, 1 tableware surface smearing sample, and 1 sample of external environment of the patient's home. Conclusions The family cluster epidemic of psittacosis was caused by exposure to the external environment contaminated by Chlamydia psittacosis. Poultry breeding should be regulated to prevent the spread of poultry infection to the human world. At the same time, the awareness of medical staff should be raised, and pathogenic testing should be carried out to confirm the diagnosis for avoiding the occurrence of severe cases and death.

Qingweisan is one of the classical prescriptions commonly used in the treatment of oral diseases. By means of Bibliometrics， the authors collected the ancient books on Qingweisan and sifted out 411 valid data， involving 116 classics of traditional Chinese medicine. The historical origin， drug composition， indications， principle of composition， dosage，and preparation of Qingweisan were statistically analyzed， and it was found that the prescription originated from the Treatise on Spleen and Stomach（《脾胃论》） by LI Dongyuan and is composed of Rehmanniae Radix， Angelica Sinensis， Cortex Moutan， Coptidis Rhizoma and Cimicifugae Rhizoma， with the functions of clearing stomach， purging fire， cooling blood and dispersing depression. And Qingweisan was mainly used to treat toothache， headache， and preference for cold and aversion to heat caused by "excessive heat in yang brightness meridian". There were 352 indications recorded， most of which followed LI Dongyuan's theory and the expanded indications reached 70 kinds. Specifically， toothache （132） was the most， accounting for 22.49% of the total indications， followed by headache （60， 10.22%）. In addition， Qingweisan was widely used in modern clinical practice for multiple system diseases， among which oral system （197） was dominant， accounting for 72.69%， followed by skin system （28， 10.33%） and digestive system （27， 9.96%）. Although the indications were wide， the pathogenesis always belonged to "upward attack of stomach fire". Through the excavation and statistical analysis of the ancient books on Qingweisan and its modern clinical application， the authors aimed to provide a more scientific reference for the research and application of classical famous prescriptions.