Pancreatic cancer is one of the most prevalent malignant tumors of the digestive system， and its incidence and mortality rates are increasing year by year. Most patients with pancreatic cancer are unable to receive surgery due to the advanced stage. Although chemotherapy regimens based on gemcitabine and fluorouracil have prolonged the survival time of patients to some extent， some patients cannot tolerate chemotherapy and hence lose the opportunity for treatment. With the advent of the era of precision medicine， molecular-targeted therapy has exhibited an excellent therapeutic efficacy and has thus become one of the most important treatment techniques for tumors； however， due to the high heterogeneity of pancreatic cancer and its complicated tumor microenvironment， molecular-targeted therapy for pancreatic cancer has not achieved notable results. Therefore， it is imperative to seek new therapeutic targets and medications to overcome this issue. This article reviews the latest advances in the research on molecular-targeted therapy for unresectable pancreatic cancer based on common molecular targets and tumor immunity-related therapeutic targets， in order to provide new treatment strategies for patients with pancreatic cancer.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Objective To explore the effects of occupational noise exposure on hypertension in Chongqing area,and to provide reference for the prevention and treatment of hypertension in noise-exposed populations.Methods Using the Chongqing key occupational disease surveillance and occupational disease hazard factor site monitoring database,the samples of adult male and female occupational noise-exposed popu-lations in Chongqing were selected by the cluster sampling,the physical examination data were collected,and the degree of hearing loss was evaluated by the binaural high-frequency mean hearing thresholds.The follow-up lasted for 3 years (2017-2019) and 5 years (2017-2021).The age,noise operation working age,BMI and blood pressure were respectively compared among the male and female respondents with different degrees of hearing loss;the Cox proportional risk regression model was adopted to analyze the relationship between de-gree of hearing loss and hypertension.Results After 3-year follow-up,the prevalence rate of hypertension in the respondents was 6.47％(308/4761),6.92％(289/4178) in males and 3.26％(19/583) in females;the de-tection rates of normal hearing,mild hearing loss and high degree of hearing loss were 46.42％,42.62％ and 10.96％ respectively.After 5-year follow-up,the prevalence rate of hypertension among the respondents was 12.44％ (431/3464),12.92％(399/3088) in males,and 8.51％(32/376) in females;the detection rates of normal hearing,mild hearing loss,and high degree of hearing loss were 64.20％,25.87％ and 9.93％ respec-tively.After 3-year,5-year follow-up,there was no significant difference in the systolic blood pressure among respondents with different degrees of hearing loss in males and females (P>0.05),but the diastolic blood pressure had significant difference (P<0.05).After adjusting the confounding factors,the 5-year risk of hy-pertension in male respondents with noise-induced mild hearing loss (binaural high-frequency mean hearing threshold 25-40 dB) was significantly increased (HR=1.25,95％CI:1.05-1.48,P<0.01).The 5-year risk of hypertension in female respondents with noise induced high degree of hearing loss (binaural high-frequency mean hearing threshold>40 dB) was significantly increased (HR=1.26,95％CI:1.10-1.44,P<0.01). Conclusion Among the populations with occupational noise exposure,the risk of developing hypertension in males with mild hearing loss is increased,and the risk of developing hypertension in males with high degree of hearing loss is increased.

With the continuous progress of research methodology in the real world and the growing maturity of artificial intelligence technology， a method for conducting “quantitative” research to guide clinical practice based on traditional Chinese medicine （TCM） diagnosis and treatment data was gradually developed. However， there is still a need for further improvements in the overall design of studies and the transformation of findings into clinical practice. Based on this， we put forward a comprehensive overall design concept and application approach for real-world study and artificial intelligence research based on clinical diagnosis and treatment data of TCM. This approach consists of five steps： Constructing a research-based database with a large sample size and high data quality； Mining and classification of core prescriptions； Conducting cohort studies to evaluate the effectiveness of core prescriptions； Utilizing case-control studies to clarify the dominant population； Establishing predictive models to achieve precision medicine. Additionally， it is imperative for researchers to establish a standardized system for collecting TCM variables and processing data， optimize the determination and measurement methods of confounding factors， further improve and promote methodologies， and strengthen the training of interdisciplinary talents. By following this research method， we anticipate that the clinical translation of research findings will be facilitated， leading to advancements in TCM precision medicine. Real-world study and artificial intelligence research share similar research foundations， and clinical applications complement each other. In the future， the two will merge together.

Adoptive cell immunotherapy has been a hot spot in tumor research in recent years. Chimeric antigen receptor T cells (CAR-T) have achieved great success in hematological tumors and have changed the current tumor treatment landscape to a certain extent. However, the application of CAR-T therapy in clinics is limited due to its serious side effects and high treatment costs. Natural killer (NK) cells are important immune cells in the body and have native cytotoxicity and well safety. NK cells based on CAR engineering (CAR-NK) have shown powerful anti-tumor activity and safety in preclinical research and could be the next generation of CAR platform-based cellular immunotherapy. This review will systematically introduce the current research status of CAR-NK cells in lymphoma.

Freshwater snail is an important biological group in aquatic ecosystem and an intermediate host of many parasites. Intestinal flora plays an important role in animal energy metabolism and resistance to pathogens. We analyzed the intestinal microbiota diversity of Radix auricularia (RA) and Planorbella trivolvis (PL) by 16S rRNA high-throughput sequencing. At the phylum level, RA had 23 phyla, including Proteobacteria (33.63%), Cyanobacteria (15.33%), Chloroflexi (13.95%), and Actinomycetes (12.99%). PL had 13 phyla, including Proteobacteria (54.88%), Bacteroidetes (28.49%), and Actinomycetes (7.65%). At the genus level, there were 445 genera in RA, including Pleurocapsa, Thiodictyon, Leptotrichia, and Nocardioides. There were 238 genera in PL, including Cloacibacterium, OM60NOR5_clade, Pseudomonas, and Rhodobacter. Ninety-three genera were the common core flora of the two snail species (all the samples were present), and 27 genera had an abundance greater than 0.5%. The structure of intestinal microbiota was significantly different between the two groups (P=0.027). We performed the functional prediction of intestinal microbiota using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and the results show that the KEGG functional composition of the intestinal flora of the two snails was similar, and the abundance of the amino acid metabolism, carbohydrate metabolism and membrane transport were large. In summary, the intestinal microbiota of the two snails was high in diversity and significantly different, but there were a large number of common core flora.
Animals ; Auricularia ; Ecosystem ; Fresh Water ; Gastrointestinal Microbiome/genetics* ; High-Throughput Nucleotide Sequencing ; Phylogeny ; RNA, Ribosomal, 16S/genetics* ; Snails

Objective To explore the effect of TCM external treatment on the patients with hyperplasia of mammary glands by meta-analysis.Methods Literatures about TCM external treatment on the patients with hyperplasia of mammary glands that were published on domestic or international magazines were extensively solicited and assessed with uniform effect criteria. The total number and valid number of patients in these literatures were counted, and the literatures were also assessed and chosen by meta-analysis with Review Manager 5.3.OR values and a 95% confidence interval (CI) were calculated and consolidated.Results Finally, totally 11 literatures and 945 patients were included in our study, of which 464 received TCM external treatment, an effective rate of 89.22%, while the control group included a total of 481 patients, an effective rate of 82.33%. TCM external treatment showed the same effect on hyperplasia of mammary glands as the oral liquid of Chinese medicines, massage and acupuncture did [OR=1.91,95%CI (0.74-4.97)]. When comparing the effect of TCM external treatment and Rupixiao oral liquid on hyperplasia of mammary glands, totally 6 literatures and 509 patients were included in the study, of which 258 received TCM external treatment, an effective rate of 97.29%, while 251 patients took Rupixiao oral liquid, an effective rate of 88.45%. TCM external treatment had a significantly better effect than Rupixiao oral liquid [OR=4.52,95%CI (1.98-10.33)].Conclusions TCM external treatment has the same effect with oral liquid of Chinese medicines, massage and acupuncture, while TCM external treatment on hyperplasia of mammary glands which promotes the circulation of qi and blood and eliminates phlegm and frees channels has a significantly better effect than Rupixiao oral liquid. It suggests that in our clinical work we should treat patients based on whatever methods they can withstand so as to improve their satisfaction.

Objective: To research and establish an analysis model for chemical drug standards to provide the reference for the standard exploration jobs. Methods:The standard variation was studied by comparing and analyzing every version standard for the same drug to look for the change rule. Results:The standard items of the drug had some change rules in indicator numbers, testing methods and limits according to the order of issue time. The standard development trends could be described by making specific indicators and drawing evolution figures of the items. Conclusion:By the standard analysis model, the same item of the same drug can be compared to provide the reference for data collecting of experts. Meanwhile, formulate standard can be calculated to provide the reference for the standard improvement without drug standards.

Adult ; Clavicle ; injuries ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods

OBJECTIVETo investigate the complications in 16 patients who had breast augmentation with polyacrylamide hydrogel injection. The distribution and late changes of the injected material was observed.

METHODSThe physical signs and symptoms of the 16 patients were classified. Ultrasound and infrared examinations or MRI were used in some cases.

RESULTSTwo patients had operations for extraction. The injection material was distributed in the muscles diffusely, or existed in the breast and subcutaneous tissue as many masses.

CONCLUSIONThe reliability of this injection method for breast augmentation is in doubt.