Objective:To investigate the effects of human glycolipid transfer protein(GLTP)on proliferation,migration and invasion of pancreatic cancer(PC)cells,and to elucidate their mechanisms.Methods:The difference in the expression levels of GLTP proteins between PC tissue and normal pancreas tissue was analyzed by University of Alabama at Birmingham Cancer Data Analysis Platform(UALCAN)Database,as well as the difference in the expression levels of GLTP protein between PC tissue and normal pancreas tissue of the PC patients with different clinicopathological characteristics.The PANC-1 cells were cultured in vitro and divided into control group(transfected with pFLAG-CMV4 plasmid)and GLTP-overexpression(GLTP-OE)group(transfected with pFLAG-GLTP plasmid).The stably GLTP transfected cells were established using the antibiotic screening method.Knock-down experiments were performed using non-specific siRNA transfected PANC-1 cells as control group and si-GLTP transfected PANC-1 cells as si-GLTP group.Western blotting method was used to detect the expression of GLTP protein in the cells in various groups,cell counting kit-8(CCK-8)method was used to detect the proliferation activities of PANC-1 cells,clone formation assay was used to detect the number of clone formation,and Transwell chamber assay were used to detect the numbers of migration and invasion cells in various groups.Transcriptomics sequencing analyses were conducted to assess the possible mechanism of GLTP in the PANC-1 cells.Western blotting method was employed to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt)proteins in the PANC-1 cells in various groups;Real-time fluorescence quantitative PCR(RT-qPCR)was used to assess the expression levels of amphiregulin(AREG)and kinase insertion domain receptor(KDR)mRNA in the cells in various groups.The mice were randomly divided into control group(injected with pFLAG-GMV4 transfected PANC-1 cells)and experimental group(injected with pFLAG-GLTP stably transfected PANC-1 cells),and the subcutaneously transplanted tumor models were prepared;the volumes and weights of the transplanted tumors of the mice in two groups were measured.Results:UALCAN database analysis showed that the expression level of GLTP protein in PC tissue was lower than that in normal pancreas tissue(P＜0.01),and there were statistically significant differences in the GLTP protein expression between PC tissue and normal pancreas tissue of the PC patients with different cancer stages(P＜0.05),tumor grades(P＜0.05),ages(P＜0.001),and genders(P＜0.05).Compared with control group,the proliferation activity(P＜0.01)and the number of clone formation(P＜0.001)of the cells in GLTP-OE group were decreased,while the numbers of migration cells(P＜0.001)and invasion cells(P＜0.01)were decreased.In the knock-down experiment,compared with control group,the proliferation activity(P＜0.01)and the number of clone formation(P＜0.05)of the cells in GLTP-OE group were increased,while the numbers of migration cells(P＜0.001)and invasion cells(P＜0.001)were increased.Compared with control group,the tumor weight and volume of the mice in experimental group were decreased(P＜0.01),following the injection of tumor cells for a period of four weeks.In the over-expression experiment,compared with control group,the expression levels of p-PI3K(P＜0.01),p-Akt-S473(P＜0.01),and p-Akt-T308(P＜0.05)proteins in the cells in GLTP-OE group were decreased;the expression levels of AREG(P＜0.01)and KDR(P＜0.01)mRNA were decreased.In the knock-down experiment,compared with control group,the expression levels of p-PI3K(P＜0.01),p-Akt-S473(P＜0.01),and p-Akt-T308(P＜0.01)in the cells in si-GLPT group were increased,and the expression levels of AREG(P＜0.01)and KDR(P＜0.05)mRNA were increased.Conclusion:Low expression levels of GLTP in PC tissue are present.The over-expression of GLTP can inhibit the proliferation,migration and invasion of PANC-1 cells,as well as the growth of subcutaneously transplanted tumors in the nude mice;its possible mechanism may be related to decreasing the activity of the PI3K/Akt signaling pathway.

Epidural labor analgesia aims to provide effective medical services to alleviate labor pain in parturients, while adhering to the principles of voluntary participation and clinical safety. In 2018, Peking Union Medical College Hospital(PUMCH)became one of the first pilot units for labor analgesia in China, and has achieved satisfactory results in high-quality development of labor analgesia. This article mainly introduces the achievements and experience of labor analgesia at PUMCH, including: (1) prioritizing maternal and infant safety, arranging personnel rationally, and developing standardized treatment processes through multidisciplinary collaboration to ensure safe and comfortable childbirth; (2) leveraging the hospital's comprehensive capabilities in emergency treatment, and improving collaborative rescue plans for critically ill parturients and newborns; (3) implementing advanced teaching methods to effectively train and conduct simulated drills for labor analgesia and rescue of critically ill parturients; (4) conducting patient education and informative lectures to help parturients acquire a scientific understanding of labor analgesia. We hope that this experience can provide reference and inspiration for other hospitals.

Objective:To identify micronuclei through the cytochalasin B blocking micronucleus method-based assay using scanning microscope, combined with the slide scanning software Metafer 4 and, accordingly, to establish a dose-response relationship between the dose of 60Co γ-rays and the frequency of micronuclei in human peripheral blood lymphocytes using artificial intelligence-based color recognition. Methods:Blood samples were collected from four healthy individuals (two men and two women) and were then exposed to varying doses of 60Co γ-ray radiation (0, 0.25, 0.5, 1, 2, 3, 4, 5 Gy) at a dosage rate of 0.74 Gy/min. Micronucleus slides were prepared as per the GBZ 128-2023 standard. The numbers of binuclear cells and micronuclei were recorded using an artificial intelligence-based color recognition analysis system. The dose-response curve was determined through fitting using the CABAS software. Then, the doses to both independent samples were estimated based on the curve. Results:Within a dose range of 0 to 5 Gy, the fitted micronucleus dose-response curve aligned with a quadratic polynomial model, with a regression equation of y = 0.032 1 D2+ 0.023 7 D+ 0.012 7 ( D denoting the dose, correlation coefficient R2=0.998). The dose estimations from the validation samples closely corresponded to the actual irradiation doses. Conclusions:Establishing the micronucleus dose-response curve provides a feasible method and basis for the rapid and accurate estimation of radiation biological doses in laboratory automation.

Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.

Objective:To summarize the precision fluid management of patients with severe blast injury in the emergency intensive care unit, so as to help patients smoothly pass through the dangerous period and recover smoothly.Methods:Based on the experience of fluid management in 6 patients admitted to the Second Affiliated Hospital Zhejiang University School of Medicine in the tanker truck explosion on 14 June, 2020. The main measures included: fluid volume management and dynamic adjustment; assessment of intake, output and urine volume, and dynamic adjustment of infusion volume and speed; monitoring of pulmonary oxygenation and timely adjustment of fluid resuscitation strategies; monitoring indexes and providing nursing care strategies for fluid management.Results:Finally, among 6 patients with severe blast injury, 5 patients were discharged from the hospital with follow-up treatment after they suffered from the shock and infection phases and refined fluid management, 1 patient died due to severe injury and ineffective rescue.Conclusions:Adopting individualized, phased, and refined liquid management strategy has clinical significance for patients with severe blast injury to smoothly pass the risk period.

ObjectiveTo explore the effects and possible mechanisms of Jianpi Bushen Formula （健脾补肾方） on radiation-induced immune function damage of mice. MethodsFifty mice were randomly divided into four groups： normal group， model group， thymosin group， high- and low-dose groups of Jianpi Bushen Formula， with 10 mice in each group. Except for the normal group， the mice in the other groups were irradiated with a single whole-body dose of 6.0 Gy X-rays to establish a radiation-injured mouse model. After the successful modeling， the low- and high-dose groups of the Jianpi Bushen Formula were given respectively 13 g/（kg·d）、 26 g/（kg·d） of the formula by gavage， while the thymosin group was given 11.7 mg/（kg·d） of thymosin by gavage， and the normal group and model group were given 0.1 ml/（10g·d） of 0.9% sodium chloride solution by gavage. Each group was administered once a day for 7 consecutive days. After the last gavage， the mice were weighed， and their spleens were separated and weighed to calculate the spleen index. The levels of interferon gamma （IFN-γ） and interleukin 2 （IL-2） in the spleen tissue were detected by enzyme linked immunosorbent assay （ELISA）. The autophagosomes in the spleen were observed by transmission electron microscopy. The mRNA expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR） in the spleen were detected by real-time fluorescent quantitative PCR. The protein expression of PI3K， Akt， and mTOR in the spleen， as well as the expression of autophagy-related proteins microtubule-associated light chain protein 3 （LC3）， Beclin1， and p62 were detected by Western blot. ResultsCompared with the normal group， the model group showed significant decreases in body weight， spleen index， and levels of IFN-γ and IL-2 in the spleen （P＜0.01）； the mRNA and protein expression levels of PI3K， Akt， and mTOR in the spleen were also significantly reduced （P＜0.01）； the expression of Beclin1 protein， the ratio of LC3-II/LC3-I significantly increased （P＜0.01）， while the level of p62 protein expression significantly decreased （P＜0.01）. And transmission electron microscopy showed a significant increase in the number of autophagosomes in the spleen and severe cell structure damage in the model group. Compared with the model group， all the above indicators in each medication group were significantly improved （P＜0.05 or P＜0.01）. In the high-dose Jianpi Bushen Formula group， partial intact cristae were visible in the fine mitochondria of the spleen， and there were more autophagosomes. In the low-dose Jianpi Bushen Formula group and thymosin group， the structure of the fine mitochondria in the spleen was relatively intact， and there were fewer autophagosomes. The improvement effect of the low-dose Jianpi Bushen Formula group was better than that of the high-dose group （P＜0.05 or P＜0.01）， and there was no significant difference between the low-dose group and the thymosin group in terms of each indicator （P＞0.05）. ConclusionJianpi Bushen Formula may alleviate the structural damage of the spleen， promote the recovery of immune function， and achieve a best effect at a low dose by enhancing the PI3K/Akt/mTOR signaling pathway in the spleen and inhibiting the over-activation of autophagy induced by radiation.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Objective:To study the effect of occupational X-ray exposure on non-cancer diseases of radiation workers.Methods:The medical X-ray workers in Chongqing mumicipality were surved in 1980. In 2020, the previous 91 medical institutions distributed across 41 districts and counties of Chongqing continued to be selected as the survyed units, including 53 grade-A top-class hospitals. Using the method of prospective cohort study, the fifth follow-up survey was conducted for Chongqing′s medical X-ray workers and the control groups in 1980 with respect to their personal information, occupational radiation exposure, disease history and others. The incidence rate, relative risk ( RR) and 95% confidence interval of diseases in each system were analyzed. Results:There were 937 individuals in this cohort. So far, 359 cases of non-cancer diseases had been counted. Compared with the control group, the relative risk RR of cardiovascular system, ophthalmology and other unclassified diseases in the exposure group were 1.50, 2.03 and 2.64 ( χ2=5.97, 3.97, 4.25, P <0.05) , respectively. The adjusted confounding factors showed that the RR of the incidence rate of cardiovascular, ophthalmic and digestive diseases in the female exposure group was generally higher than that in the control group ( RR=2.33, 2.59, 7.55; χ2= 7.28, 4.17, 8.64, P < 0.05) , respectively. The RR of the incidence rate of cardiovascular and ophthalmic diseases in exposure group was generally higher than that in the control group among 25-29 year-old workers ( RR=2.26, 5.07; χ2 =8.22, 4.91, P < 0.05) , respectively. For compasion between the the accumulated dose groups, the incidence rate of cardiovascular system, ophthalmology and digestive system diseases in the exposure group was generally higher than that in the control group ( RR=1.86, 2.91, 3.59; χ2= 9.83, 8.21, 5.58, P < 0.05) , respectively. Conclusions:The non-cancer risk of X-ray workers exposed to long-term occupational exposure was increased, among which the risk of cardiovascular system, digestive system, ophthalmic diseases and others might be related to the occupational exposure.

China’s chronic disease management suffers from problems such as unclear institutional function， insufficient information technology application， and weak regulation support. On the basis of current chronic disease management condition in China， this paper proposes to apply the concept of “people-centered” integrated health management to community chronic disease management and discusses the content and procedure of establishing an integrated community-based chronic disease management model driven by massive databases. The model innovatively combines technology integration， data integration and service integration， and can accurately and efficiently realize the "people-centered" full-course health management of various chronic diseases. Shanghai has provided integrated community-based chronic disease management service for 1.98 million citizens through applying this model. The model warrants further effectiveness and economic evaluation. This study provides precious experience for the development of chronic disease prevention and treatment in China.

Objective:To investigate the clinical effects of acupuncture therapy on post-hemiplegia neck and shoulder pain.Methods:Eighty patients with post-stroke hemiplegia with neck and shoulder pain who received treatment in Department of Acupuncture, Massage and Physiotherapy, Zhejiang Provincial Armed Police Corps Hospital between December 2020 and June 2021 were included in this study. They were randomly assigned to undergo either conventional rehabilitation treatment and analgesic tablets (control group, n = 40) or conventional rehabilitation treatment, analgesic tablets and acupuncture therapy in combination (observation group, n = 40). Traditional Chinese medicine efficacy, western medicine efficacy, degree of neurological deficits, ability of daily living, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, traditional Chinese medicine efficacy and western Chinese medicine efficacy in the observation group were significantly higher than those in the control group (87.50% vs. 52.50%, 82.50% vs. 55.00%), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (17.50% vs. 42.50%, χ2 = 21.48, 16.33, 9.12, all P < 0.05). In the control group, National Institutes of Health Stroke Scale (NIHSS) score measured after treatment was significantly lower than that measured before treatment [(7.58 ± 1.87) points vs. (14.87 ± 1.36) points, t = -9.58, P < 0.001], and Barthel Index (BI) measured after treatment was significantly higher than that measured before treatment [(53.78 ± 1.34) points vs. (37.92 ± 1.74) points, t = 6.35, P < 0.001]. In the observation group, NIHSS score measured after treatment was significantly lower than that measured before treatment [(5.44 ± 2.11) points vs. (14.51 ± 0.34) points, t = -12.69, P < 0.001], and BI measured after treatment was significantly higher than that measured before treatment [(62.02 ± 0.68) points vs. (37.73 ± 1.58) points, t = 7.45, P < 0.05]. BI post-measurement in the observation group was significantly higher than that in the control group [(62.02 ± 0.68) points vs. (53.78 ± 1.34) points, t = 4.35, P < 0.05]; NIHSS score post-measurement in the observation group was significantly lower than that in the control group [(5.44 ± 2.11) points vs. (7.58 ± 1.87) points, t = -8.48, P < 0.05]. Conclusion:Acupuncture treatment for post-hemiplegia neck and shoulder pain can markedly reduce pain in patients, improve prognosis and increase clinical efficacy.