Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Background Exposure to volatile organic compounds (VOCs) has been observed in both living and working environments. Volatile organic compounds metabolites (VOCMs) in urine can be used to assess the exposure to VOCs and potentially cause adverse effects on human body. Objective To quantitatively evaluate urinary VOCMs and their associations with renal function damage, and further trace the characteristics of potential environmental exposure to provide scientific evidence for effective prevention measures. Methods The study included a total of 6028 samples from four cross-sectional studies in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018, with exposure and health outcomes matched. Generalized linear models were employed to assess the associations of urinary VOCMs (urinary creatinine adjusted) with urinary protein levels and estimated glomerular filtration rate (eGFR), with coviriables including gender, age, body mass index, education, smoking, alcohol consumption, exercise frequency, diabetes, and hypertension. Weighted quantile sum (WQS) approach was utilized to analyze the effects of mixed exposure and to rank the contribution of individual VOCMs. The associations between VOCMs and associated living environments and occupational exposure characteristics were further investigated. Results Among the enrolled study participants (n=6028), a total of 11 urinary VOCMs were measured, with 10 metabolites having a positive rate of over 80% (84.59%-99.99%). There were 604 individuals (10.0%) having urinary protein abnormalities and 2831 individuals (47.0%) with eGFR reduced. Through a single and a multiple generalized linear model, 5 VOCMs exhibited statistically significant associations with urinary protein abnormalities and/or reduced eGFR levels (P<0.05): N-acetyl-S-(N-methylaminocarbonyl)-L-cysteine (AMC), N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEM), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHB), 2-hydroxy-2-phenylacetic acid (MAD), and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MB3). The WQS index indicated a significantly positive association between VOCMs and urinary protein abnormalities, and DHB contributed the most. The analysis on the potential sources of VOCs exposure showed that those who worked as a private entrepreneur or an employee (vs. government employees), rent houses (vs. owned real estate), had less number of rooms in the residence, fueled cars at self-service gas stations, and inhaled paint fumes in the past 48 h associated with higher VOCMs (P < 0.05) and DHB contributed the most. Conclusion Multiple VOCMs in urine are associated with significantly kidney function injuries. The mixture exposure to VOCMs is significantly associated with higher risks of urinary protein abnormalities. Occupational category, housing ownership, ways to fuel a car, and inhalation of paint odors are closely related with VOCMs levels.

Objective: To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children. Methods: A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations. Results: The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05). Conclusion Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

Objective:To explore the application value of optical surface monitoring system (OSMS) volume rendering technique (VRT) body surface imaging in intensity-modulated radiotherapy for thoracic tumors.Methods:A retrospective case series study was performed. The clinical data of 65 patients with thoracic tumors treated with intensity-modulated radiotherapy at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from September 2021 to October 2022 were retrospectively analyzed. In the first treatment,after cone-beam computed tomography (CBCT) scan and correction, VRT body surface images were obtained by using OSMS. In subsequent treatment, the VRT image was used as the benchmark and the 6-dimensional bed was automatically positioned to record the 6-dimensional bed positioning value. The CBCT scan was performed to record the translation and rotation errors of left-right direction (X-axis), head-foot direction (Y-axis) and front-rear direction (Z-axis). After the calibration of the 6-dimensional automatic bed shifting, the new real-time deltas (RTD) value of digital imaging and communications in medicine (DICOM) body surface image was recorded, and the new VRT image was obtained. CBCT registration error value was defined as VRT image-guided setup error. The sum of CBCT registration error value and moving bed movement value was defined as the body surface marker line-guided setup error. The sum of CBCT registration error value and the recorded DICOM image RTD value was defined as the theoretical error of DICOM image-guided setup. The advantages and disadvantages of VRT image, body surface marker line and DICOM image-guided setup were compared and analyzed.Results:There were 42 males and 23 females in 65 patients with thoracic tumors, and the age [ M ( Q1, Q3)] was 58 years (51 years, 64 years). The linear errors [ M ( Q1, Q3)] of VRT image-guided setup in X, Y and Z axes were 0.6 mm (0.3 mm, 1.2 mm), 1.2 mm (0.5 mm, 2.4 mm) and 1.1 mm (0.5 mm, 1.9 mm); and the rotational errors were 0.4° (0.1°, 0.7°), 0.4° (0.1°, 0.6°) and 0.4° (0.2°, 0.6°). The linear errors of the marker line-guided setup were 1.6 mm (0.9 mm, 2.6 mm), 2.2 mm (1.1 mm, 3.8 mm) and 1.0 mm (0.4 mm, 1.8 mm); and the rotational errors were 0.7° (0.3°, 1.2°), 0.5° (0.2°, 0.8°) and 0.5° (0.2°, 0.8°). The linear errors of the DICOM image-guided positioning were 1.1 mm (0.6 mm, 1.9 mm), 2.1 mm (1.0 mm, 3.4 mm) and 1.3 mm (0.6 mm, 3.1 mm), and the rotational errors were 0.6° (0.2°, 1.1°), 0.7° (0.3°, 1.1°), 0.7° (0.2°, 1.1°). Compared with the marker line-guided setup, except for Z-axis linear error ( P = 0.218), the VRT-guided setup errors were low (all P < 0.001). Compared with the DICOM imaging-guided setup, the VRT image-guided setup linear error and rotational error in X-, Y- and Z-axis were low (all P < 0.01). Conclusions:VRT image-guided setup is superior to traditional body surface marker setup and DICOM imaging setup; OSMS VRT body surface imaging can effectively improve the setup accuracy and stability of intensity-modulated radiotherapy for thoracic tumors, and reduce the setup errors.

Objective To explore the application efficacy and safety of oblique ultrasound-guided techniques in PICC puncture,in order to provide guidance and references for clinical application.Methods Through convenient sampling,654 patients from a tertiary A hospital in Zhejiang Province from March to December 2022 were selected as the study subjects.The random numbers were generated through Excel table functions and they were randomly grouped into 3 groups:A,B,and C.The ultrasound short axis method,long axis method,and oblique axis method were employed to guide PICC puncture catheterization,respectively.The success rate of PICC puncture,the number of subcutaneous adjustments of the puncture needle,puncture time,and the occurrence of puncture complications(such as hematoma,puncture of the posterior wall of blood vessels,accidental injury to arteries,and accidental injury to nerves)were recorded during the catheterization process in 3 groups.Results A total of 654 patients completed the study,including 215 in group A,219 in group B,and 220 in group C.The success rate of first-time puncture in the group C(86.36％)was higher than that in group A(73.95％)and group B(63.93％),and there was a statistically significant difference among 3 groups(P＜0.001).The subcutaneous adjustment frequency of the puncture needle was 1(1,1)in group C,1(1,2)in group A,and 1(1,2)in group B.The difference between 3 groups was statistically significant(P＜0.001);the puncture time of group C was shorter than that of group A and group B,and the difference was statistically significant(P＜0.001).There was a statistically significant difference in the puncture time between 3 groups(P＜0.017);the pairwise comparison of the number of subcutaneous needle adjustments and the success rate of a puncture between 3 groups showed that there was a statistical difference between group C and group A,and between group C and group B(P＜0.017),while there was no statistical difference between group A and group B(P＞0.017).There was statistical significance(P＜0.05)among 3 groups in terms of complications such as accidental nerve injury and puncture of the contralateral vascular wall by puncture needle,but there was no statistical significance in terms of accidental arterial injury and hematoma occurrence among 3 groups.Conclusion Compared with the short axis approach and the long axis approach,the ultrasound oblique axis approach guided PICC puncture has statistical differences in the success rate of a puncture and the incidence of puncture complications,etc.It is recommended to use the ultrasound oblique axis approach during PICC puncture.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

Objective To study the clinical application value of abdominal pressure band in CT-guided puncture biopsy of lower lung nodules.Methods A retrospective analysis was conducted on 100 patients who underwent lower lung nodule punc-ture biopsy at the Cancer and Radiotherapy Center of Tongji Hospital affiliated to Huazhong University of Science and Technol-ogy from January to December 2022.They were divided into abdominal pressure band group and control group.There were 40 patients in abdominal pressure band group,among which abdominal pressure bands were applied during the puncture process.There were 60 patients in control group who did not use abdominal pressure bands during the puncture process.The CT scan frequency,puncture depth,success rate,intraoperative time,incidence of complications,and radiation dose for puncture biopsy were compared between the two groups.Results The median value of CT scan frequency during puncture biopsy in ab-dominal pressure band group was 5 times,with a success rate of 100％(40/40).The median value of intraoperative time was 7.9 min,and the incidence of complications was 10％(4/40).The median value of radiation dose was 210.4 mGy·cm.The median value of CT scan frequency during puncture biopsy in control group was 8 times,with a success rate of 86.7％(52/60).The me-dian value of intraoperative time was 13 min,and the incidence of complications was 40％(24/60).The median value of radiation dose was 287.7 mGy·cm.Differences in five indicators were statistically significant between the two groups(all P＜0.05).Conclusion Application of the abdominal pressure bands in lower lung nodule puncture biopsy can significantly reduce the number of scans,shorten surgical time,reduce the radiation dose received by patients,and have a higher success rate and lower incidence of complications.Utilization of pressure band should be promoted in clinical practice.

Objective To explore the efficacy and safety of subretinal injection of conbercept in treating refractory neovascular age-related macular degeneration(nAMD).Methods In this prospective clinical study,17 eyes of 17 pa-tients diagnosed with refractory nAMD at the Department of Fundus Disease,the Affiliated Eye Hospital of Nanchang Uni-versity from March 2022 to September 2023 were enrolled.The 10 g·L-1 conbercept was injected into the subretinal area of the macular area using a 41G ultra-fine microneedle.If retinal exudation was found in the macular area by optical coherence tomography during the follow-up,the intravitreal injection of 10 g·L-1 conbercept was performed.The best corrected vis-ual acuity(BCVA),central macular retinal thickness(CMT),number of injections and complications were recorded before and 1,3,6,and 12 months after the operation.Results Compared with the preoperative values,the BCVA of patients significantly improved(all P＜0.001)1,3,6 and 12 months postoperatively.There was no significant change in BCVA at each time point after operation(all P＞0.05).Compared with pre-operation,CMT of patients significantly decreased at 1,3,6 and 12 months after operation(all P＜0.001).From 1 month to 12 months after the operation,the CMT of patients gradually decreased(all P＜0.001).Pearson correlation analysis showed that there were positive correlations between pre-operative BCVA and preoperative CMT,preoperative BCVA and 12-month postoperative BCVA(r=0.643,P=0.005;r=0.634,P=0.006).During the treatment,the number of anti-vascular endothelial growth factor injections in 17 eyes was(1.35±0.61)times,with 1 time in 12 eyes,2 times in 4 eyes,and 3 times in 1 eye.Correlation analysis showed that the number of injections was positively correlated with preoperative CMT(r=0.664,P=0.004).No intraoperative or postop-erative complications related to the operation occurred in 17 eyes.Conclusion Subretinal injection of conbercept,which can reduce CMT and improve visual prognosis,is a safe and effective treatment method for refractory nAMD.

Objective:To explore the clinical application value of Bodyfix fixation device in stereotactic body radiotherapy (SBRT) for elderly patients with lung cancer.Methods:The clinical data of 63 elderly patients with lung cancer who received SBRT in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to October 2021 were retrospectively analyzed. According to different fixation methods, the patients were divided into Bodyfix combined with vacuum bag fixation device group (Bodyfix group, 20 cases) and 4D respiratory gating technology combined with vacuum bag fixation device group (vacuum bag group, 43 cases). Cone beam CT (CBCT) was used for position verification before each treatment, linear and rotational errors in the horizontal (X), head-to-foot (Y), front-to-back (Z) directions were recorded.Results:The linear errors of Bodyfix group in the X, Y and Z directions were 1.7 mm (1.3 mm, 3.0 mm), 4.6 mm (4.3 mm, 5.3 mm) and 1.3 mm (0.8 mm, 2.8 mm), and the rotational errors were (0.46±0.04)°, (-0.48±0.05)° and 0.64°(0.38°, 1.07°); the linear errors of vacuum bag group in the X, Y and Z directions were 2.1 mm (1.6 mm, 3.3 mm), 2.8 mm (1.8 mm, 3.7 mm) and 3.0 mm (2.3 mm, 3.8 mm), and the rotational errors were (0.69±0.04)°, (-0.70±0.04)° and 0.64° (0.42°, 0.86°). The differences in linear errors in the Y and Z directions and rotational errors in the X and Y directions between the two groups were statistically significant ( P values were <0.001, <0.001, 0.003 and 0.007). Conclusions:Compared with the 4D respiratory gating technology, the Bodyfix fixation device has smaller rotational errors in the X and Y directions and linear errors in the Z direction. It can be used as an effective method of postural fixation for SBRT in elderly patients with lung cancer.