Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1⁺ NK cells (t = 8.45, P < 0.05) and DX5⁺ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1⁺ DX5⁺ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1⁺ NK cells (t = 4.58, P < 0.05) and PD-1⁺ DX5⁺ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5⁺ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5⁺ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5⁺ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5⁺ NK cell subsets.

Purpose To evaluate the added value of time of flight(TOF)and point spread dispersion(PSF)reconstruction in mediastinal lymph node metastasis of lung cancer in 18F-FDG PET/CT imaging.Materials and Methods Sixty-eight lung cancer patients with mediastinal lymph node metastasis who underwent PET/CT examination in the First People's Hospital of Foshan from March 9,2020 to July 23,2021 were analyzed retrospectively.The different methods,including ordered subsets estimation maximization(OSEM),OSEM+TOF,OSEM+PSF,OSEM+TOF+PSF,were used to reconstruct the images.The resolution of different reconstruction algorithms for mediastinal lymph node metastasis of lung cancer,as well as the differences of signal-to-noise ratio(SNR)and standard uptake value(SUV)were compared,respectively.Results The highest values of SUVmean,SUVmax and SNR were obtained via OSEM+TOF+PSF method,which increased by 21.99%,22.86%and 60.14%,compared with conventional OSEM method(t=28.321,19.11,11.059,all P<0.01).The difference percentage in smaller lesions that diameter≤22 mm was significantly higher than that in larger lesions that diameter>22 mm(24.1%vs.21.1%,25.3%vs.19.3%,70.6%vs.63.3%;Z=-3.658,-4.313,-2.154,all P<0.05),and the difference percentage in low contrast lesions that SNR≤15.31 was significantly higher than that in high contrast lesions that SNR>15.31(23.6%vs.21.4%,25.3%vs.21.1%,85.7%vs.46.0%;Z=-3.519,-2.336,-5.106,all P<0.05).Among the evaluation results of lesion detectability of different reconstruction algorithms,OSEM+TOF+PSF image showed the mediastinal lymph node metastasis most clearly(87.4%of the lesions were clearly existing),which was significantly higher than that of OSEM image(73.1%of lesions were clearly existing)(χ2=11.704,P=0.001),however,the proportion of lesions clearly existing in OSEM+PSF image did not significantly increase compared with OSEM image(73.1%vs.75.8%;χ2=0.361,P=0.548).Conclusion The combination of TOF and PSF can significantly improve the detection ability,SNR and SUV of mediastinal lymph node metastasis of lung cancer,especially in small and low contrast lesions.

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.
Humans ; Tigecycline/pharmacology* ; Escherichia coli/metabolism* ; Reactive Oxygen Species/therapeutic use* ; Plasmids ; Anti-Bacterial Agents/metabolism* ; Escherichia coli Infections/microbiology* ; Bacteria/genetics* ; Microbial Sensitivity Tests

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, a growing prevalence of racial and ethnic discrimination occurred when many Americans struggled to maintain healthy lifestyles. This study investigated the associations of racial and ethnic discrimination with changes in exercise and screen time during the pandemic in the United States. METHODS: We included 2,613 adults who self-identified as non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, or Hispanic from the Health, Ethnicity, and Pandemic study, a cross-sectional survey conducted among a nationally representative sample of United States adults between October and November 2020. We assessed self-reported racial and ethnic discrimination by measuring COVID-19-related racial and ethnic bias and examined its associations with changes in exercise and screen time using multivariable logistic regression models. We analyzed data between September 2021 and March 2022. RESULTS: COVID-19-related racial and ethnic bias was associated with decreased exercise time among non-Hispanic Asian (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.13 to 1.89) and Hispanic people (OR, 1.91; 95% CI, 1.32 to 2.77), and with increased screen time among non-Hispanic Black people (OR, 1.94; 95% CI, 1.33 to 2.85), adjusting for age, sex, education, marital status, annual household income, insurance, and employment status. CONCLUSIONS Racial and ethnic discrimination may have adversely influenced exercise and screen time changes among racial and ethnic minorities during the COVID-19 pandemic in the United States. Further studies are needed to investigate the mechanisms through which racial and ethnic discrimination can impact lifestyles and to develop potential strategies to address racial and ethnic discrimination as a barrier to healthy lifestyles.

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Objective:To compare the expression difference of Toll like receptor (TLR) and inflammatory factors between pancreatic cancer and normal pancreatic epithelial cells, and explore the correlation between TLR and inflammatory microenvironment.Methods:Normal pancreatic duct epithelium cells (HPNE) and pancreatic cancer cells (Panc-1 and Mia-PACA-2) were cultured and proteins were obtained. The expression of TLR family protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and myeloid differentiation factor 88 (MyD88) were examined by western blot in HPNE, Panc-1 and Mia-PACA-2. The correlations between TLR and inflammation cytokines of pancreatic cancer were analyzed by Pearson correlation analysis.Results:Compared with HPNE, the TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 were highly expressed in Panc-1 and Mia-PACA-2 (all P<0.05). Compared with Panc-1, the expression of TLR2 and TLR4 in Mia-PACA-2 were increased obviously, while the TLR9 expression was mildly decreased (all P<0.05). The expression of IL-6 in HPNE was found less than that in Panc-1 (0.52±0.03 vs. 0.76±0.04) and Mia-PACA-2 (0.52±0.03 vs. 1.12±0.09) with statistical differences ( P<0.05). Similarly, the expression of TNF-α was found significantly less than that of Panc-1 cells (0.63±0.04 vs. 0.87±0.06) and Mia-PACA-2 cells (0.63±0.04 vs. 0.95±0.10) with statistical differences (all P<0.05). The expression of IL-6 was found positively correlated with expressions of TLR2 ( r=0.964), TLR4 ( r=0.968), TLR7 ( r=0.844), TLR8 ( r=0.668) (all P<0.05), and the expression of TNF-α was found positively correlated with expressions of TLR2 ( r=0.805), TLR4 ( r=0.893), TLR7 ( r=0.847), TLR8 ( r=0.780) (all P<0.05). In contrast with HPNE, the expression of MyD88 was found highly expressed in Panc-1 (0.91±0.10 vs. 0.33±0.03) and Mia-PACA-2 (1.14±0.10 vs. 0.33±0.03) (all P<0.001). Compared with Panc-1, the expression of MyD88 in Mia-PACA-2 was obviously increased (1.14±0.10 vs. 0.91±0.10) with statistical difference ( P=0.048). Conclusion:The TLR family may play a critical role in development of pancreatic cancer by regulating the immune microenvironment, and its mechanism may be through upregulating MyD88 which functions as key signal transduction.

Objective:To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy (PD)associated postoperative pancreatic fistula (POPF), total complications, peri-operative death and postoperative in-hospital days.Methods:From January 2020 to August 2021, 148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial. Patients were randomly assigned into octreotide group ( n=74) and control group ( n=74). Octreotide group was subcutaneously injected with 0.1 mg (1 ml) octreotide after preoperative anesthesia, and was subcutaneously injected with the same dose every 8 hours for 5 days, with a total of 16 doses. Control group was injected with 1 ml normal saline in the same way, and relevant clinical data and indicators of the two groups were recorded. The primary endpoint was clinically relevant pancreatic fistula, and the secondary endpoints were total complications, perioperative death and postoperative in-hospital days. Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD. Results:120 patients were finally enrolled, including 61 in octreotide group and 59 in control group. There were no significant differences on age, gender ratio, body mass index, preoperative surgery rate of jaundice reduction, preoperative major biochemical indicators, operation time, intraoperative blood loss, pancreatic duct diameter, pancreatic texture and pathological type composition ratio. The total incidence of clinical relevant POPF was 8.3%, and there were no significant differences on biochemical leakage (4.9% vs 8.5%, P=0.435), grade B fistula (4.9% vs 8.5%, P=0.435) and grade C fistula (1.6% vs 1.7%, P=0.981). The total complication incidence (24.5% vs 28.8%, P=0.601), perioperative mortality (0 vs 3.3%, P=0.147) and postoperative in-hospital days (20.6±11.1 d vs 19.5±12.2 d, P=0.633) were not significantly different between two groups. Univariate analysis showed that preoperative serum albumin level <30 g/L( P<0.001) and pathological type of pancreatic ductal adenocarcinoma ( P=0.036) were independent risk factors for POPF after PD, while multivariate analysis found no statistically significant risk factors. Conclusions:Octreotide can neither reduce the incidences of POPF, total complications and postoperative mortality, nor shorten postoperative in-hospital days. However, for patients with preoperative hypoproteinemia and (or) the pathological type of pancreatic duct adenocarcinoma, the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.

Objective:To explore the value of diffusion tensor imaging (DTI) in evaluating the effects of hyperbaric oxygen therapy (HOT) in treating spinal cord injury.Methods:The modified Allen′s method was used to induce a traumatic spinal cord injury in 30 rats who were then divided randomly into an injured group and a treatment group, each of 15. The treatment group was given HOT twice a day for 3 days, then once a day for a total of 4 weeks. The injured group did not receive HOT. DTI was performed (along with Basso-Beattie-Bresnahan (BBB) evaluation) at 0h, 6h, 24h, as well as 3, 7, 14, 21 and 28 days after the operation. Two-factor repeated measures ANOVA was conducted to analyze any differences in the DTI results: the fractional anisotropy, mean apparent diffusivity, radial diffusivity and axial diffusivity, as well as the BBB scores. LSD t-tests were performed to analyze the significance of the differences at different time points.Results:At each time point after 24h the average FA value of the treatment group was significantly higher than the injured group′s average, while its average MD and RD values were significantly lower. Beyond 14 days the average AD value of the treatment group was significantly higher than that of the injured group. The treatment group′s average BBB score was also significantly higher at all the time points beyond 3 days.Conclusions:DTI results can evaluate spinal cord function and provide valuable information for the dynamic assessment of hyperbaric oxygen therapy after a traumatic spinal cord injury, and the therapy promotes the recovery of motor function, at least in rats.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been infected rapidly and is generally susceptible to population. Moreover, it has become the most serious public health problem in the world. In the process of coronavirus disease 2019 (COVID-19) treatment, the traditional Chinese medicine (TCM) intervention has achieved positive efficacy and which is widely recognized. However, the COVID-19 epidemic is still very serious, especially due to the characteristics of asymptomatic infection such as concealment, limitations and subjective symptoms, which has increased the difficulty of prevention and control. In view of asymptomatic infection, isolation is the main management. There is little mention of specific treatment options in each version of COVID-19 treatment plan. Through systematic study of TCM theory, we explored the way of diagnosis and treatment of asymptomatic infections. Based on the theory of latent evil, clearing away latent pathogens to truncate the course of disease and reduce the incidence. Based on the theory of prevention of disease, strengthen the lung and stomach to protect the place from pathogen and prevent the transmission of disease evil. It is supplemented by accurate treatment according to individual, timing and local conditions, in order to provide reference for the treatment of asymptomatic infection.

Objective:To investigate the clinical efficacy and safety of 90Sr- 90Y β-ray low dose applicator, topical timolol maleate, and their combination in the treatment of superficial infantile hemangioma (IH). Methods:From May 14, 2013 to April 11, 2017, 400 children (126 males, 274 females, age 5.3(3.9, 7.1) months) with superficial IH in Department of Nuclear Medicine, the First People′s Hospital of Foshan were prospectively enrolled. All patients were randomly divided into 4 treatment groups according to the proportion of 1∶1∶1∶1 by the method of random number table: topical timolol maleate (group A, control group), 90Sr- 90Y β-ray low dose applicator (group B), single course applicator combined with timolol (group C), and multi-course applicator combined with timolol (group D). Lesions were followed up to the 104 th week (W104). Cure rate of W104 was considered as primary end point. Efficacy and safety of different treatment were compared. Kruskal-Wallis rank sum test, Mann-Whitney U test, and logistic regression analysis were used for statistical analysis. Results:Totally, 438 lesions in 400 cases were included in this prospective study. There was no significant difference in baseline characteristics among 4 groups ( χ2 values: 1.709-11.616, H values: 3.681-7.653, all P>0.05). As of W104, 11 lesions (2.51%, 11/438) were lost follow-up, 32 lesions (7.31%, 32/438) were with early withdrawal, 357 lesions (81.51%, 357/438) were cured, 15 lesions (3.42%, 15/438) were with residual, 23 lesions (5.25%, 23/438) were with rebound growth, and no serious adverse events occurred in the 4 groups. Multivariate analysis showed that lesions thickness (<3 mm vs ≥ 3 mm, odd ratio ( OR)=16.689, 95% CI: 7.908-35.223; χ2=54.555, P<0.001) and treatment (considering group A as reference category, OR (95% CI) of group B, C and D were 16.842(6.179-45.901), 4.801(2.167-10.638) and 39.127(10.468-146.243), respectively; χ2=47.663, P<0.001) were independent factors affecting the cure rate of W104. 90Sr- 90Y low-dose fractionation radiotherapy was significantly better than topical timolol maleate ( OR=16.842, 95% CI: 6.179-45.901), and the combination with timolol could significantly reduce the cumulative absorbed dose of radiotherapy (group D vs B: 16(8, 16) vs 16(16, 24) Gy; z=-4.947, P<0.001). Conclusion:90Sr- 90Y low dose applicator therapy is superior to topical timolol maleate for superficial IH, and the combination with timolol could significantly reduce the cumulative absorbed dose of applicator.