Objective:To investigate personal exposures to nitrogen oxides(NOX)and nitrogen di-oxide(NO2)and the influence of baseline personal characteristics,living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai.Methods:In this panel study,91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study.The study was conducted in summer and winter.The participants were followed for three times with an interval of at least two weeks.Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic.Twenty-seven participants completed follow-up visits in both seasons.We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity in-formation through questionnaire/diary.The linear mixed model was used to analyze the associations be-tween potential influencing factors and personal NOX and NO2 exposure levels.Results:There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities.The ave-rage 24 h personal exposures to NO2 and NOX(volume fraction)in Tianjin participants were 18.0 x 10-9 and 26.2 × 10-9 in summer,and 31.0 x 10-9 and 54.9 x 10-9in winter,respectively;and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7 x 10-9and 100.0x10-9in summer,and 45.5 x10-9 and 139.2 x 10-9 in winter,respectively.The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city,season,gender,average daily cooking times,and ambient NO2 concentrations measured at fixed-site monitoring stations.In addition to the above factors,the personal NOX exposure levels were also significantly associ-ated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking,average daily home time,cooking energy type,residential distance from main traffic road,and use of kitchen ventilators.Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai,were significantly lower in summer than that in winter,and were significantly and positively associated with ambient NO2 concen-trations measured at fixed-site monitoring stations.In addition,personal NOX exposure levels were signifi-cantly lower in females than in males,and personal NO2 exposure levels were significantly positively asso-ciated with average daily cooking times and significantly inversely associated with average daily home time.For every interquartile range(IQR)increase(12.7 × 10-9)in ambient NO2,the personal NO2 exposure levels increased by 27.5％(95％CI:17.0％-38.9％),and personal NOX exposure levels in-creased by 16.1％(95％CI:7.1％-25.8％).Conclusion:Season,city and ambient NO2 concentra-tions are significant influencing factors of personal exposure levels of NO2and NOX At the same time,the personal exposures levels of NO2 are also affected by lifestyle factors.Our study provides scientific evi-dence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Objective:To investigate the influence of combining therapy of massage on sacro-2 to sacro-4 spinal cord reflexion area and anal dilatation therapy on constipation after cerebral apoplexy and promote the rehabilitation of defecation function in patients with constipation after stroke.Methods:Aandomized controlled study method was chosen, 80 patients with constipation after cerebral apoplexy treated in Guangzhou Traditional Chinese Medicine Hospital from August 2018 to July 2019 were selected as research subjects by convenience sampling. The enrolled patients were divided into 2 groups, 40 to the observation group and 40 to the control group by random number table method. On the basis of routine constipation related nursing measures, the control group was given anal dilatation therapy, while the observation group′s treatment was given massage on sacro-2 to sacro-4 spinal cord reflexion area combined with anal dilatation therapy. Before intervention and after intervention, the changes of therapeutic effect of constipation effect, constipation symptoms scores and the degree of neurological deficit were all compared between the two groups.Results:There were 22 males and 18 females in the observation group; age ranged from 40 to 75 (63.33 ± 8.49) years old; in the control group, there were 23 males and 17 females, aged 41-74 (63.03 ± 7.60) years old. Before intervention, there was no statistically significant difference in constipation symptom scores and neurological deficits between the two groups (both P>0.05). After intervention, the score of constipation symptoms was (3.80 ± 2.05) points and the score of the degree of neurological deficit was (7.58 ± 2.69) points in the observation group, both lower than (5.18 ± 3.52) points and (8.90 ± 2.73) points in the control group with statistically significant differences between the two groups ( t values were respectively -2.13 and -2.19, both P<0.05). The total efficacy of the observation group was 97.50% (39/40), which was significantly higher than 87.50% (35/40) of the control group with statistically significant differences between the two groups ( χ2 = - 2.11, P<0.05). Conclusions:Nursing intervention of massage on sacro-2 to sacro-4 spinal cord reflexion area combined with anus dilatation therapy on constipation after cerebral apoplexy can effectively reduce the symptoms of constipation and lowered the degree of neurological deficit, which is beneficial to the functional rehabilitation of patients with cerebral apoplexy.

Due to traditional professional divisions, the practice of endoscopy by gastro-intestinal surgeons in China remains controversial. However, with the evolution of treatment philo-sophies, medical technology, and equipment advancements, a trend of integration between tradi-tional surgery and endoscopy is emerging. Gastrointestinal surgeons performing endoscopy can maxi-mize patient benefits, and they naturally possess advantages in conducting endoscopic procedures. It is recommended to further establish entry thresholds for surgeons to perform endoscopy, provide standardized endoscopic training for surgeons, and coordinate efforts at the administrative depart-ment. With the support of artificial intelligence, more patients can receive minimally invasive, indivi-dualized, and precise treatments.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Objective To analyze the clinical phenotypes and mutation types of children with X-linked Alport syndrome(XLAS)with mutations in COL4A5 gene,and to explore the relationship between children with XLAS and nephrotic syndrome nephritic type.Methods Thirty-two children with COL4A5 gene mutations detected by second-generation sequencing and finally diagnosed with Alport syndrome at Guangzhou Red Cross Hospital affiliated with Jinan University and the First People's Hospital of Guangzhou between April 2016 and April 2023 were included,and their clinicopathological features and gene mutation characteristics were retrospectively analyzed.Results The mean age of onset of disease in children with XLAS was(3.68±2.07)years old,the mean age at diagnosis(6.56±2.95)years old,12 cases(37.5%)started with isolated hematuria,8 cases(25%)started with hematuria and proteinuria,12 cases(37.5%)started with nephrotic syndrome nephritic phenotype,and the positive family history of the children was found in 11 cases(34.4%),ocular lesions were found in 3 cases(9.37%),ear lesions in 6 cases(18.75%),and 7 cases(21.87%)were found to have developed chronic kidney disease(CKD)in the later follow-up.21 children underwent renal tissue puncture biopsy,and electron microscopy showed thinning of the basement membrane(diffuse or segmental)in 13 cases(61.9%),and uneven thickness of the basement membrane in 8 cases(38.09%);light microscopy showed thinning of the basement membrane in 13 cases(61.9%);light microscopy showed thinning of the basement membrane in 8 cases(38.09%);and light microscopy showed thinning of the basement membrane in 3 cases(11.5%).(38.09%);light microscopy:focal segmental glomerulosclerosis(FSGS)in 2 cases(9.52%),mesangial proliferative glomerulonephritis(Ms PGN)in 11 cases(52.38%),and minimal change disease(MCD)in 8 cases(38.09%).The type of mutation was categorized as missense mutation in 12 cases(37.5%),shear site mutation in 9 cases(28.12%),nonsense mutation in 6 cases(18.75%),deletion mutation in 3 cases(9.37%),and code shift mutation in 2 cases(6.25%).Genetic mutations were present in 22 cases(68.75%);spontaneous mutations were present in 10 cases(27.02%).Conclusions Children with XLAS have atypical clinical manifestations and pathologic features in the early stage of the disease,and the progress is slow,and some of them are easy to be misdiagnosed as nephrotic syndrome nephritis type in the early stage,so it is important to improve the genetic test for this disease as early as possible,and to make reason-able drug choices to predict the prognosis scientifically.

Objective:To evaluate the efficacy of arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique for the treatment of tibial avulsion fracture of posterior cruciate ligament (PCL).Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with tibial avulsion fracture of PCL, who were admitted to First People′s Hospital of Huizhou from January 2018 to October 2022. There were 19 males and 13 females, with age range of 18-65 years [(42.8±15.0)years]. By the Meyers-Mckeever classicfication, 27 patients were type II, and 5 type III. All the patients were treated with arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique to fix PCL tibial avulsion fracture at the insertion point. The fracture reduction was observed by X-ray films before discharge. Three months postoperatively, the fracture healing was observed by CT imaging, and the stability of knee joint was evaluated by posterior drawer test. The knee active range of motion, visual analogue score (VAS), Lysholm score, and International Knee Documentation Committee (IKDC) score were used to evaluate the pain and knee function before operation, at 3 months after operation, and at the last follow-up. Intraoperative and postoperative complications were observed.Results:All the patients were followed up for 6-36 months [(19.7±8.7)months]. The X-ray films showed satisfactory reduction of the fracture before discharge, and the CT showed that the fracture line was blurred to various degrees at 3 months after operation. Two patients had degree I positive posterior drawer test at 3 months after operation, and the rest were negative. The knee active range of motion was improved from 54.2°(45.0°, 70.0°) preoperatively to 124.8°(120.0°, 130.0°) at 3 months postoperatively and to 130.6°(125.0°, 135.0°) at the last follow-up (all P<0.01). The VAS was decreased from 5.1(3.0, 7.0)points preoperatively to 1.2(1.0, 2.0)points at 3 months postoperatively and to 0.1(0.0, 0.0)points at the last follow-up (all P<0.01). The Lysholm score was improved from 31.2(24.3, 37.0)points preoperatively to 73.6(69.3, 78.8)points at 3 months postoperatively and 92.6(91.0, 95.0)points at the last follow-up (all P<0.01). The IKDC score was increased from (20.9±7.1)points preoperatively to (59.2±8.9)points at 3 months postoperatively and to (77.5±7.0)points at the last follow-up (all P<0.01). Compared with 3 months after operation, the last follow-up showed significantly improved knee active range of motion, significantly decreased VAS, and significantly increased Lysholm score and IKDC score (all P<0.05). No intraoperative nerve vascular injury, postoperative incision infection, or lower limb venous thrombosis was observed. Conclusion:Arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique can achieve good reduction and high healing rate in patients with tibial avulsion fracture of PCL, with improved joint mobility, relieved pain, good recovery of knee joint function, and few complications.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic expo-nential decay model.The potential effect of thimerosal on protein function,particularly for thiol-containing proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.

Objective:To analyze the risk factors of hepatocellular carcinoma microvascular invasion (MVI) and to construct a preoperative prediction clinical scoring system.Methods:A retrospective analysis was made on 113 patients with hepatocellular carcinoma undergoing hepatectomy at Zhongshan Hospital from March 2018 to Jun 2019.Postoperative pathology confirmed 35 cases with microvascular invasion.Results:The multivariate logistic regression model showed that the maximum tumor diameter( OR: 1.028, 95% CI: 1.001-1.005), the smoothness of the capsule edge( OR: 0.208, 95% CI: 0.062-0.699), the positive circulating tumor cells (CTC)( OR: 3.728, 95% CI: 1.029-13.501) and abnormal prothrombin(PIVKA-Ⅱ)( OR: 1.001, 95% CI: 1.000-1.002) were risk factors for MVI. The area, sensitivity and specificity of the clinical score constructed by assigning 1 point to each risk factor were 0.906, 74.29% and 92.31%, respectively. Clinical scores of 0, 1, 2, 3, and 4 predict MVI positive rates of 0 (0/26), 9.09% (3/33), 28.57% (6/21), 77.78% (14/ 18), 85.71% (12/14). Conclusions:Tumor maximum diameter>62 mm, PIVKA-Ⅱ>115 mAU/ml, unsmooth tumor capsule and CTC in peripheral blood are independent high risk factors in patients with MVI.

Objective:To explore the application value of detecting circulating tumor cells (CTC) before liver transplantation for predicting the recurrence and survival of hepatocellular carcinoma (HCC).Methods:From October 2015 to October 2019, 62 HCC patients at Affiliated Zhongshan Hospital were collected and analyzed by Cyttel method before liver transplantation. CTC was determined by X-tile software and Kaplan-Meier method for determining the optimal cutoff value of CTC before liver transplantation and the relationship between CTC and clinical factors was analyzed. Univariate and multivariate COX regression analyses were performed for determining the independent risk factors affecting the prognosis. Kaplan Meier method was employed for describing the survival curve of tumor-free survival and overall survival after transplantation.Results:The optimal preoperative critical value of CTC was 3.2 ml. CTC ≥3/3.2 mL was set as CTC positive group while CTC <3/3.2 mL CTC negative group. The positive/negative CTC before transplantation was significantly correlated with preoperative Alpha-fetoprotein(AFP) level, maximal tumor diameter, lymph node metastasis, liver transplantation criteria and degree of differentiation ( P<0.05). Univariate and multivariate COX regression models indicated that the number of preoperative CTC (HR: 1.262, 95%CI: 1.069-1.489, P=0.006) and microvascular invasion (HR: 2.657, 95%CI: 1.120-6.305, P=0.027) were independent risk factors for tumor-free survival after transplantation while microvascular invasion (HR: 3.738, 95%CI: 1.219-11.459, P=0.027) was the sole independent risk factor affecting the overall survival of HCC after transplantation. Statistically significant difference existed between preoperative CTC positive/negative and tumor recurrence or metastasis (no recurrence, intrahepatic recurrence, and distant metastasis)( χ2=7.790, P=0.020). The disease-free survival rates of 1/2/3-year CTC-negative/positive patients were 82.90%, 68.70%, 58.90% and 49.00%, 29.40%, 22.10%; the 1/2/3-year overall survival rates of preoperative CTC-negative/positive patients were 85.50%, 77.10%, 69.79% and 64.90%, 47.20%, 40.50% respectively. The disease-free survival curve of CTC-negative patients was significantly higher than that of CTC-positive counterparts ( P<0.001) and the overall survival curve of CTC-negative patients was significantly higher than that of CTC-positive counterparts ( P<0.005). Conclusions:Preoperative CTC detection has certain application value in evaluating the prognosis of liver cancer after liver transplantation, which has important clinical significance and application prospects.