Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

[Objective] In view of the crucial role of indole propionic acid in the treatment of tumor immune checkpoint blockade and further revealing its mechanism, our study intended to design and synthesize 1-[¹⁸F]-fluoroethyl-indole propionic acid (1-[¹⁸F]-IPA), and evaluate it as a tumor PET imaging agent. [Methods] The precursor 1-(2-p-toluenesulfonic acid oxygen ethyl)-methyl indole propionate underwent nucleophilic substitution reaction with ¹⁸F^-. The crude product was separated and purified by high-performance liquid chromatography and the intermediates were collected. Finally, 1-[¹⁸F]-IPA was obtained by hydrolysis. The clarity of the product was measured by visual inspection, the pH value was determined by precision test paper, and the radiochemical purity and stability were determined by high-performance liquid chromatography. In order to determine the biodistribution of 1-[¹⁸F]-IPA in normal mice, ICR mice were intravenously injected with 1-[¹⁸F]-IPA (0.2 mL, 7 MBq), and sacrificed at 5, 15, 25, 45, 75 and 120 min and dissected. Micro-PET imaging was performed and analyzed in BxPC-3 tumor-bearing nude mice. Student t test was used to compare the biodistribution of tissues and organs at different time points. [Results] The total preparation time of 1-[¹⁸F]-IPA was 35-40 min, the radiochemical yield was (45±5)%, and the radiochemical purity was more than 95%. The product solution was clear without particles, and the pH value was 6.5, which had good stability in vitro and in vivo. The results of biodistribution in healthy ICR mice showed that except for the brain, 1-[¹⁸F]-IPA had a certain uptake in all major organs, with the most obvious uptake in the liver, gallbladder and kidneys. The radioactivity in the gallbladder gradually increased with time and reached (39.86±6.56)%ID/g at 120 min, but bone uptake did not change significantly with time. Micro-PET/CT showed that there was radioactive uptake at the tumor 30 min after injection of 1-[¹⁸F]-IPA in Dutch BxPC-3 nude mice, but it was not obvious. At this time, SUVmax was about 55.18±14.62. Consistent with the results of biodistribution, the brain uptake was low at each time point. [Conclusion] In summary, 1-[¹⁸F]-IPA with short preparation time and high yield is expected to be a tool to probe tryptophan indole metabolism pathway and further reveal tumor immune resistance.

Objective:To investigate the satisfaction levels of the rural elderly in Dafeng district of Yancheng, Jiangsu province with the contracted family doctor services, and to identify the factors that influence their satisfaction.The findings of this study will provide valuable insights for improving the quality of the contracted family doctor services offered to the rural elderly population.Methods:The study utilized the stratified cluster sampling method to select elderly individuals aged 60 years and above from Dafeng district, Yancheng city for a questionnaire survey.Specifically, the study focused on elderly individuals who had participated in contracted family doctor services for more than six months.The survey aimed to gather information on the elderly population's general situation, as well as their understanding, utilization, and satisfaction with contracted family doctor services.The satisfaction of contracted family doctor services was analyzed using the chi square test and multivariate Logistic regression to identify the influencing factors.Results:The study surveyed 385 elderly individuals from rural areas who had contracted family doctor services.The results showed that 88.3%(340/385)of respondents were satisfied with the services they received.Additionally, 99.2%(382/385)of those surveyed were aware of the contracted family doctor services, and 81.8%(315/385)had received basic medical services from their signed-up doctors.The results of a multifactor analysis that examined the factors influencing the overall satisfaction of elderly patients with their contracted family doctor services revealed several significant factors.Specifically, being female( OR=2.557, 95% CI: 1.122-5.830, P=0.026)and unmarried( OR=7.355, 95% CI: 1.850-29.237, P=0.005), supporting the contracted family doctor services system( OR=18.442, 95% CI: 1.732-195.973, P=0.016), believing that the contracted medical institutions had excellent hardware facilities( OR=9.918, 95% CI: 2.313-42.526, P=0.002)and providing high-quality health services for the elderly( OR=8.723, 95% CI: 1.556-48.908, P=0.014), as well as experiencing improved health status after signing the contract( OR=5.006, 95% CI: 1.764-14.201, P=0.002)were all significant factors influencing their satisfaction.These findings suggest that these factors are important considerations for improving the satisfaction of elderly patients with their contracted family doctor services. Conclusions:The contracted family doctor services provided in Dafeng district, Yancheng city have been well received by the rural elderly population.Factors such as gender, marital status, attitude towards the contracted family doctor services system, improvements in health status after contracting the service, quality of the hardware facilities at the contracted medical institution, and availability of health services specifically tailored for the elderly all play a role in determining the level of satisfaction among the contracted elderly population.To better serve the elderly population, it is crucial that we prioritize their needs.This can be achieved by improving the level of "suitable aging" in the contracted services and enhancing the satisfaction of family doctors who provide these services.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Objective: To investigate the outbreak of mumps in a remote village school of Zhaoqing City, to evaluate and vaccine effectiveness ( VE ) of mumps containing vaccine (MuCV), so as to provide reference for the formulation of epidemic prevention and control strategies. Methods: Through on site case investigations and interviews, case data and epidemic related epidemiological information were obtained. Descriptive and retrospective cohort studies were used to analyze the epidemic characteristics, explore risk factors, and evaluate the protective effect of vaccines. Results: Totally 166 cases of mumps were found, and all of them were students. The total attack rate was 7.79% and the outbreak lasted for 60 days. The first case occurred on October 11th and the last case occurred on December 9th in 2018. Most of the cases aged from 10 to 13 years old, accounting for 66.27%. There were 96 male patients and 70 female patients, with no statistically significant sex difference in the incidence rate ( χ 2=2.40, P >0.05). Involving 28 classes, 11 of which had an incidence rate more than 10%, mainly distributed in grades 2, 4 and 6. There were statistically significant differences in incidence rates among different grades ( χ 2=96.89, P <0.01) and different floors ( χ 2=67.35, P < 0.01 ), with the third floor higher than the other floors. Twelve out of 58 boarding pupils were cases, and boarding pupils were 1.89 times higher in risk of contracting mumps than day students ( RR=1.89, 95%CI =1.10-3.23). Pupils without being given the shot of MuCV were higher in the infection rate than those having the shot ( χ 2=5.70, P <0.05), and the VE % was 35% (95% CI = 7%- 55%). The VE % of one dose was 34% (4%-54%), while the effectiveness of protection was declined with time ( χ 2 trend =6.53, P < 0.05). The effectiveness of vaccine almost diasappeared six years after the shot ( χ 2=1.12, P >0.05). Conclusion Delayed case report and isolation, low rate of receiving MuCV, and decreasing effectiveness of one shot MuCV are closely assocaited with the outbreak and ongoing spread of the epidemic.

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

【Objective】 To investigate the diagnostic efficacy of a novel bladder cancer detection system utilizing a urine cell processing kit for urine sample preservation and detection. 【Methods】 Patients with primary persistent gross hematuria and high recurrence risk of bladder cancer after transurethral resection of bladder tumor were prospectively enrolled between Dec.2021 and Mar.2022. Urine specimens were either added to (experimental group) or not added to (control group) the urine cell processing kit and were fixed on Day 0, Day 3 and Day 7. The sensitivity and specificity of the two groups were compared after the cells were fixed, produced, stained and read with body fluid cytology total staining technique. 【Results】 The sensitivity and specificity of the experimental group on Day 0 were 82.50% (33/40) and 87.50% (14/16), respectively; those of the control group were 79.49% (31/39) and 82.35% (14/17), respectively. On Day 3, the sensitivity and specificity of the experimental group were 76.32% (29/38)and 81.25% (13/16), respectively; those of the control group were 52.78% (19/36) and 78.57% (11/14), respectively. On Day 7, the sensitivity and specificity of the experimental group were 71.43% (25/35) and 72.22% (13/18), respectively; those of the control group were 35.71% (10/28) and 60.00% (9/15), respectively. The sensitivity of the experimental group on Day 3 and Day 7 was significantly higher than that of the control group (P<0.05). 【Conclusion】 This bladder cancer urine cytology detection system provides clear diagnostic advantages and can be used as an auxiliary examination before cystoscopy for patients with hematuria and those at high risk of bladder cancer recurrence. It can also be used as a bladder cancer screening tool for pre-screening a large sample of people in order to achieve early diagnosis and treatment of bladder cancer.

Objective:In order to develop an appropriate care service system and care security system for the elderly in urban communities, it is necessary to gain a comprehensive understanding of their needs and utilization of care services, as well as the cost of care and the factors that influence it.This will provide a theoretical basis for developing effective countermeasures.Methods:A stratified random cluster sampling method was utilized to conduct a questionnaire survey on individuals aged 60 and above in the Xuzhou urban community.The survey aimed to gain insight into the needs, utilization, and expenditure of care services for the elderly.To analyze the factors influencing care expenditure, a single factor χ2 test and Tobit regression model were employed. Results:In our survey of 1 623 elderly individuals, it was found that 32.4%(526 people)had been bedridden for more than one day in the past year and were unable to care for themselves.Of the elderly who are bedridden, 393 individuals(74.7%)have received care services from professional institutions, with a focus on medical care(312 people, 79.4%)and rehabilitation care(95 people, 24.2%).In terms of financial expenditures, 91.7% of respondents(1 489 people)reported spending zero yuan in the past year, while 6.0%(96 people)spent between 1 and 4 999 yuan.Only 1.0%(17 people)reported spending between 5 000 and 9 999 yuan, and 1.3%(21 people)spent 10 000 yuan or more.The findings from the univariate analysis revealed that various factors, including marriage, age, medical expenses, and life satisfaction had a significant impact on the care expenses of the elderly(all P<0.05).Furthermore, the Tobit regression model demonstrated that certain variables were particularly influential in determining care expenses.Specifically, elderly individuals with higher monthly income(Me=3.114), advanced age(Me=3.458), knowledge of care insurance(Me=7.647), disability(Me=10.998), no spouse(Me=14.387), and dementia(Me=20.473)had significantly higher care expenses. Conclusions:The survey conducted in Xuzhou suggests that the demand for care services is high, yet the utilization rate remains low, leading to a significant burden of care costs.To address these challenges, we must prioritize the care needs of disabled, mentally retarded, and advanced-age elderly individuals.We should also focus on enhancing medical and rehabilitation care services, improving the overall quality of elderly care, and promoting the development of a comprehensive elderly care service system and care security system that caters to the specific needs and financial constraints of the elderly population.

Objective:To evaluate the efficacy of bedside gastric ultrasound in guiding enteral nutrition therapy in the patients with spontaneous cerebral hemorrhage.Methods:Sixty-one patients with spontaneous intracerebral hemorrhage in the intensive care unit (ICU) of our hospital, aged 18-60 yr, with the European malnutrition risk screening score in 2002 was ≥ 3, who could not eat orally, were selected.All patients received decompression or aneurysm clipping under general anesthesia.Patients were divided into 2 groups using a random number table method: control group ( n=30) and ultrasound group ( n=31). Nutrient infusion pump was used to infuse standard whole protein formula enteral nutrition continuously through a nasogastric tube.In control group, gastric residual volume, residual traits and bowel sounds were evaluated according to gastric drainage to start or adjust enteral nutrition treatment.In ultrasound group, the antral motility index and gastric residual volume were monitored by the modified antral single section method under ultrasound to start or adjust enteral nutrition treatment.The starting time of enteral nutrition, time to reach the target feeding amount, rate of reaching the target feeding standard within 96 h, interruption of enteral nutrition, duration of hospitalization in ICU, and occurrence of intraperitoneal hypertension, aspiration, diarrhea, gastrointestinal bleeding and new pulmonary infection during enteral nutrition therapy were recorded. Results:Compared with control group, the initiation time of enteral nutrition and time to reach the target feeding amount were significantly shortened, the interruption rate of enteral nutrition was decreased, the rate of reaching the target feeding standard within 96 h was increased, the incidence of aspiration and new pulmonary infection was decreased ( P<0.05), and no significant change was found in the duration of hospitalization in ICU and incidence of intraperitoneal hypertension, diarrhea and upper gastrointestinal bleeding in ultrasound group ( P>0.05). Conclusions:Bedside gastric ultrasound-guided enteral nutrition therapy can improve the therapeutic effect with higher safety in the patients with spontaneous intracerebral hemorrhage.