Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

A retrospective investigation was conducted to analyze the occupational exposure history, clinical manifestations, laboratory tests, imaging findings, and diagnosis and treatment of two cases of sequential latent occupational acute organotin poisoning. Both patients were successively employed in the same enterprise, engaged in crushing of waste polyvinyl chloride plastics, and thus potentially exposed to organotin hazards. Within several days of employment, both patients developed discomfort symptoms, and central nervous system impairment was observed, including short-term memory loss, slow response, and cognitive dysfunction. Hypokalemia was detected in both cases. Cranial magnetic resonance imaging showed abnormalities (multiple ischemic lesions in the bilateral frontal and parietal lobes), and urinary tin was positive. Symptoms relieved in both patients after treatments with tin-exclusion, potassium supplementation, and neurotrophic treatment. Based on the GBZ 26-2007 Diagnostic Criteria of Occupational Acute Trialkyltin Poisoning, and combined with worksite survey of occupational health and exclusion of cerebrovascular disease, viral encephalitis, and autoimmune encephalitis and other neurological disorders, both patients were diagnosed with mild occupational acute trialkyltin poisoning. Sequential latent occupational acute organotin poisoning is prone to misdiagnosis, with great difficulty in etiological identification. Comprehensive assessment of occupational exposure history and biomarker testing are essential for differential diagnosis. Early recognition and intervention improve prognosis, highlighting the need for strengthened occupational health supervision and protection in high-risk work posts.

Objective:To explore the application value of preoperative serum vitamin A level in the prediction of benign or malignant pulmonary nodules.Methods:It was a retrospective cohort study. A total of 1 224 patients who underwent surgery for pulmonary nodules at the General Hospital of the People′s Liberation Army from January 2016 to December 2018 were consecutively included. The demographic information, postoperative pathological results, pulmonary CT findings and preoperative serum vitamin A test results were collected. The preoperative serum vitamin A levels of patients with lung cancer and benign pulmonary nodules were compared pairwise using the χ2 test. Logistic regression analysis was used to analyze the relevant factors for the occurrence of lung cancer and a stratified analysis was performed too. Prediction models for the benignity or malignancy of pulmonary nodules were constructed based on the results of multivariate logistic regression analysis. The efficacy of the models was evaluated, and the optimal preoperative prediction model was determined. The application value of preoperative serum vitamin A levels in predicting the benignity or malignancy of pulmonary nodules was then analyzed. Results:Of the 1 224 patients, postoperative pathology confirmed 1 044 cases with lung cancer and 180 cases with benign pulmonary nodules. The mean preoperative serum vitamin A level of patients with lung cancer was significantly lower than that in patients with benign pulmonary nodules (0.90 vs 1.06 μmol/L) ( Z=-3.493; P<0.001). Preoperative serum vitamin A level was a negative related factor for the occurrence of lung cancer ( OR=0.663, 95% CI: 0.484-0.914) ( P=0.011). In patients aged<60 years ( OR=0.623, 95% CI: 0.428-0.912), male ( OR=0.649, 95% CI: 0.438-0.976), with a body mass index≥24 kg/m 2 ( OR=0.634, 95% CI: 0.420-0.974), no family history of tumors ( OR=0.634, 95% CI: 0.440-0.923), no smoking history ( OR=0.619, 95% CI: 0.412-0.941), no drinking history ( OR=0.625, 95% CI: 0.424-0.933), with pulmonary nodules measuring 1-3 cm in diameter ( OR=0.643, 95% CI: 0.455-0.920), and with solid pulmonary nodules ( OR=0.681, 95% CI: 0.466-1.001), the preoperative serum vitamin A levels were significantly negatively correlated with the occurrence of lung cancer (all P<0.05). The prediction model incorporating preoperative serum vitamin A, CT characteristics of pulmonary nodules (nodule diameter, density), and clinical characteristics (age, gender) showed the best predictive efficacy for the benignity or malignancy of pulmonary nodules (the area under the curve was 0.792). Conclusions:Among patients receiving surgical treatment for pulmonary nodules, the preoperative serum vitamin A level of patients with lung cancer is lower than that of patients with benign pulmonary nodules. The preoperative serum vitamin A level is a negative associated factor for the occurrence of lung cancer. A combined model incorporating the preoperative serum vitamin A level provides a good prediction of benign or malignant pulmonary nodules.

Objective To observe the value of motion freeze technology(MFT)for improving the quality of cone-beam CT(CBCT)images of renal artery aneurysms.Methods Twenty patients with renal artery aneurysms who would receive transcatheter arterial embolization were prospectively enrolled.Renal artery angiography was performed under the guidance of CBCT,and motion artifacts were processed using MFT.Then subjective and objective evaluation of images before and after MFT correction were performed,aimed on displaying of renal artery,parent artery and vascular tree in target area,and the mean value(mean)and standard deviation(SD)of unit density pixels,margin sharpening error rate of blood vessels were measured and calculated.Results After MFT correction,the displaying of renal artery on maximum intensity projection images and parent artery on reconstructed CBCT images were significantly better than those before correction(both P＜0.05),clear vascular trees could be automatically extracted using Flightplan for Liver software,SD and margin sharpening error rate of blood vessels of renal artery aneurysm significantly decreased but mean significantly increased on CBCT images(all P＜0.05).Conclusion MFT could effectively improve the quality of CBCT images of renal artery aneurysms.

Objective The equilibrium solubility and oil-water partition coefficient of caffeic acid in different pH environments were determined,and its biopharmaceutical classification system(BCS)classification was speculated.The dissolution curve of caffeic acid tablets was determined,and the above parameters were substituted into the rat PBPK model for modeling.Gastroplus software was used to predict the in vitro and in vivo correlation of caffeic acid tablets.Methods Quantitative analysis of caffeic acid was performed by a high-performance liquid chromatography in this research,the chromatographic column was Agilent Eclipse Plus C18(4.6 mm×250 mm,5 μm),the mobile phase was 0.32%glacial acetic acid solution-methanol(70∶30),the flow rate was 1.0 mL·min-1,the detection wavelength was 323 nm,the column temperature was 25℃,the injection volume was 10 μL.The equilibrium solubility,solubility volume(DSV)and oil-water partition coefficient(P)of caffeic acid in different pH buffers were measured by the shake flask method and n-octanol-water system,and its BCS classification was speculated.The dissolution curves of caffeic acid tablets in water,pH1.2,pH4.5 and pH6.8 were determined.The Z-Factor values of these dissolution curves were analyzed using Gastroplus software.The relevant parameters were substituted into the physiological pharmacokinetic(PBPK)model of rats to simulate the in vivo pharmacokinetic(PK)curve of rats.Compared with the measured PK curve that was reported previously,the correlation between in vivo and in vitro was speculated.Results The equilibrium solubility of caffeic acid in pH1.2,pH4.5 and pH6.8 were 0.676,1.266 and 4.624 mg·L-1,and the DSV were 443 787,236 967 and 64 879 mL,which showed that caffeic acid was an insoluble drug which had a strong pH dependence in dissolution;The oil-water partition coefficients(P)of caffeic acid in water,pH1.2 buffer,pH4.5 buffer and pH6.8 buffer were 4.33(logP=0.64),28.87(logP=1.46),19.77(logP=1.30)and 0.28(logP=-0.56),which indicated that caffeic acid was a BCS Ⅱ drug with high permeability.The results of the Cmax,tmax and AUC of caffeic acid in rats obtained by a software simulation was 0.358 μg·mL-1,0.39 h and 0.320 μg·h-1·mL-1,which was basically matched with the results[Cmax∶(0.250±0.037)μg·mL-1、tmax∶(0.33±0.12)h、AUC∶(0.303±0.024)μg·h-1·mL-1]that reported previously,so was the PK curves.Conclusion Caffeic acid is a drug with low solubility and high permeability.It is speculated that caffeic acid is a BCS Ⅱ drug,and its tablets show a high correlation in vivo and in vitro in rats.

AIM:To investigate the impact of Bruton tyrosine kinase(BTK)on Alzheimer disease(AD)-like pathology through the NIMA(never in mitosis gene A)-related kinase 7(NEK7)-nucleotide-binding oligomerization do-main-like receptor protein 3(NLRP3)pathway.METHODS:5xFAD and wild-type(WT)mice aged 2,4 and 6 months were utilized to assess the expression of BTK,NEK7 and NLRP3 proteins in the hippocampus and cortex via Western blot and immunofluorescence.Co-immunofluorescence was conducted to identify the interaction between NEK7 and NLRP3 in the brains of 4-month-old mice.Three-month-old mice were divided into a control group and an ibrutinib treatment group,receiving intraperitoneal injections of ibrutinib(10 mg/kg)or solvent for 14 d,and were then subjected to behavioral as-sessments including learning and memory tests using the Morris water maze and Y-maze.Wild-type mice were induced with an AD model by intracerebroventricular injection of Aβ42.Morris water maze tests were performed after 14 d to eva-luate learning and memory,followed by measurement of BTK protein levels in the brain via Western blot.BV2 microglial cells were treated with ibrutinib,followed by LPS or Aβ42 stimulation.Western blot analysis was conducted to measure the protein levels of NEK7,NLRP3,BTK and p-BTK(Y223),while immunofluorescence was used to assess the protein expression of ASC,caspase-1,NEK7 and NLRP3.RESULTS:The levels of BTK,NEK7 and NLRP3 in the brains of 5×FAD mice were significantly elevated compared to WT mice,with observed interaction between NEK7 and NLRP3 in the 5xFAD mouse brains.Ibrutinib treatment significantly improved learning and memory functions in mice compared to the AD group.In BV2 cells,pre-treatment with ibrutinib effectively suppressed the NLRP3 inflammasome pathway and NEK7 proteins in response to Aβ42 stimulation.CONCLUSION:BTK plays a regulatory role in AD-like pathology through the NEK7-NLRP3 pathway both in vivo and in vitro.

BACKGROUND:In recent years,a variety of lasers have been widely used in various diseases related to stomatology,including the prevention and treatment of dental caries. OBJECTIVE:To investigate the effect of neodymium-doped:yttrium aluminum perovskite(Nd:YAP)laser combined with two remineralizers on early enamel caries in vitro. METHODS:Early enamel caries models in vitro were artificially established by 60 enamel blocks and randomly divided into 6 groups(n=10).Group A did not undergo any treatment but underwent extracorporeal pH circulation.Group B underwent remineralization of dentin(the main component of casein phosphopeptide-amorphous calcium phosphate composite)and extracorporeal pH circulation.Group C underwent remineralization treatment of Sensodyne toothpaste(the main component of bioactive glass)and then underwent extracorporeal pH circulation.Group D received Nd:YAP laser irradiation and extracorporeal pH circulation.Group E was treated with Nd:YAP laser irradiation,with remineralization of dentin,and then with extracorporeal pH circulation.In group F,Nd:YAP laser irradiation was performed,and then Sensodyne toothpaste was used for remineralization,and the extracorporeal pH circulation was performed;the remineralization treatment was conducted twice a day,and the experimental period was 20 days.Group G was a normal control group,without caries or remineralization,but only underwent extracorporeal pH circulation.After the experiment,the microhardness,morphology and Ca/P ratio of the dental enamel surface were measured in each group. RESULTS AND CONCLUSION:(1)The surface microhardness value of dental enamel in groups B,C and D was higher than that in group A(P<0.000 1);the surface microhardness value of dental enamel in groups E and F was significantly higher than that in groups B,C and D(P<0.000 1),and the surface microhardness value of dental enamel in group F was significantly higher than that in group E(P<0.000 1).(2)Scanning electron microscopy showed that there were a lot of demineralized pores on the enamel surface of group A.There were mineral deposits on the enamel surface of group B,which were uneven and loose.In group C,there were a lot of mineral deposits on the enamel surface,and demineralized pores were found between the calcified masses.The enamel surface of group D was relatively flat;the demineralized pores were significantly smaller than that of group A,and the enamel column interstitium was damaged.In group E,the mineral deposits on the enamel surface were thicker and the demineralized pores were significantly reduced.The mineralized substances deposited on the enamel surface of group F were most dense and uniform and the demineralized pores were small.(3)The Ca/P ratio on the enamel surface of groups B and C was significantly higher than that of group A(P<0.000 1);the Ca/P ratio on the enamel surface of group E was significantly higher than that of groups B,C and D(P<0.000 1),and the Ca/P ratio on the enamel surface of group F was higher than that of group E(P<0.001).(4)These findings indicate that bioactive glass,casein phosphopeptide-amorphous calcium phosphate composite,and Nd:YAP laser after enamel demineralization can promote the remineralization of early enamel caries.Nd:YAP laser combined with bioactive glass or casein phosphopeptide-amorphous calcium phosphate composite can further strengthen the remineralization of dental enamel caries,and the combination of Nd:YAP laser and bioactive glass has the best effect.

METHODS: We retrospectively collected CT scan data from 276 patients with pathologically confirmed primary bone tumors from 4 medical centers in Guangdong Province between January, 2010 and August, 2021. A convolutional neural network (CNN) was employed as the deep learning architecture. The optimal baseline deep learning model (R-Net) was determined through transfer learning, and an optimized model (S-Net) was obtained through algorithmic improvements. Multivariate logistic regression analysis was used to screen the clinical features such as sex, age, mineralization location, and pathological fractures, which were then connected with the imaging features to construct the deep learning fusion model (SC-Net). The diagnostic performance of the SC-Net model and machine learning models were compared with radiologists' diagnoses, and their classification performance was evaluated using the area under the receiver operating characteristic curve (AUC) and F1 score. RESULTS: In the external test set, the fusion model (SC-Net) achieved the best performance with an AUC of 0.901 (95% CI: 0.803-1.00), an accuracy of 83.7% (95% CI: 69.3%-93.2%) and an F1 score of 0.857, and outperformed the S-Net model with an AUC of 0.818 (95% CI: 0.694-0.942), an accuracy of 76.7% (95% CI: 61.4%-88.2%), and an F1 score of 0.828. The overall classification performance of the fusion model (SC-Net) exceeded that of radiologists' diagnoses. CONCLUSIONS The deep learning fusion model based on multi-center CT images and clinical features is capable of accurate classification of osseous and chondroid matrix mineralization and may potentially improve the accuracy of clinical diagnoses of osteogenic versus chondrogenic primary bone tumors.
Humans ; Deep Learning ; Bone Neoplasms/diagnostic imaging* ; Retrospective Studies ; Tomography, X-Ray Computed/methods* ; Neural Networks, Computer ; Male ; Female ; ROC Curve ; Algorithms

【Objective】 To explore the current status and development trend of research on external therapies in traditional Chinese medicine (TCM) for insomnia over the past 10 years through bibliometrics and visual analysis, to provide references for further research on the topic. 【Methods】 Literature relating to TCM external therapies for insomnia from January 1, 2012 to December 31, 2021 was retrieved from Chinese databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and from the Web of Science Core Collection (WOSCC) for English articles. CiteSpace, VOSviewer, Scimago Graphica, and NoteExpress software were used to analyze publication volumes of the papers and how they were distributed in different journals, as well as to visualize the data of the countries, authors, institutions, and keywords. 【Results】 A total of 6 085 papers were obtained, of which 5 592 were from the Chinese databases and 493 were from the English database, with their publication volumes growing steadily year on year. Approximately 45 countries and regions were found to have published research on the topic. In terms of Chinese publications, the author with the most papers published was CHEN Yunfei from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine. The closest collaboration was between LIU Chengyong from the Affiliated Hospital of Nanjing University of Chinese Medicine and YUE Zenghui from Hunan University of Chinese Medicine. In terms of English publications, the author with the most papers published was MAO Junj from Sloan-Kettering Cancer Research Center, USA, and LAO Lixing from the University of Hong Kong was his closest partner in collaboration. Heilongjiang University of Chinese Medicine was the institution with the most Chinese publications, and Shanghai University of Traditional Chinese Medicine was the one with the most English papers published. Studies on the topic were published in 386 Chinese journals and 205 English journals, respectively. Nowadays, the clinical application of TCM external treatments for insomnia, the selection of meridians and acupoints, therapies for insomnia and its related diseases are research hotspots. The combined use of different TCM external therapies is a trend in the treatment of insomnia and its concomitant diseases, especially in the fields of oncology, nursing, and psychiatric disorders. The exploration of mechanisms of TCM external therapies for insomnia is also a key direction for future research. In clinical practice, the commonly used external therapies for insomnia include acupuncture, ear-acupressure with beans, acupoint application, etc. The commonly selected acupoints are auricular points, Sishencong (EX-HN1), Shenmen (HT7), etc. The frequently studied meridians are Ren, Du, Qiao, etc. The insomnia concomitant diseases are depression, stroke, anxiety, etc. 【Conclusion】 A wealth of research results have been accumulated in the treatment of insomnia by TCM external therapies, but authoritative research results are not so many. Therefore, institutions in different countries should strengthen communications and cooperation, and researchers should be encouraged to make innovations and breakthroughs on the basis of inherited TCM external therapies, so as to produce more valuable research results and improve TCM external therapies for providing better treatments for patients with sleep disorders.

The in-depth study of the intervention of endometriosis （EMS） with Chinese medicines has revealed many pathways that can be regulated by Chinese medicines in the treatment of EMS. Chinese medicinal compound prescriptions， single Chinese herbal medicines， or their active ingredients treat EMS via the signaling pathways discussed in this paper. They can directly or indirectly regulate the expression of key molecules in the corresponding signaling pathways to inhibit the proliferation of endometriotic cells and the inflammatory changes of endometrial tissue， promote the apoptosis of endometriotic cells， change the pain threshold， and reduce endometriotic cell invasion， so as to achieve the therapeutic effects of inhibiting EMS progression， improving endometrial receptivity， and reducing ovarian injury. The following details are based on relevant studies conducted both at home and abroad. Curcumol can inhibit angiogenesis and promote cell apoptosis by blocking the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Icariin can reduce inflammation and promote cell apoptosis by blocking the nuclear factor-kappa B signaling pathway. Puerarin can suppress cell proliferation and promote cell apoptosis by inhibiting the mitogen-activated protein kinase （MAPK） signaling pathway and blocking the estrogen signaling pathway. Naringenin has the ability to activate the MAPK signaling pathway to promote cell apoptosis. Imperatorin can inhibit cell proliferation and promote cell apoptosis by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Resveratrol can inhibit cell proliferation and alleviate fibrosis and adhesion by blocking the transforming growth factor-beta signaling pathway. Paeonol can inhibit angiogenesis by blocking the hypoxia-inducible factor 1 signaling pathway. The above summary can serve as a reference for the future clinical treatment or experimental research of EMS with Chinese medicines.