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Shengqiang Fu,1,* Binbin Gong,1,* Siyuan Wang,1 Qiang Chen,1 Yifu Liu,1 Changshui Zhuang,2 Zhilong Li,1 Zhicheng Zhang,1 Ming Ma,1 Ting Sun1 1Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Urology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting SunDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, 330000, Jiangxi Province, People’s Republic of ChinaEmail 361439919033@email.ncu.edu.cnBackground: DLEU2 is a long noncoding RNA considered important in the progression of many cancers. However, correlations between DLEU2 and kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC) have rarely been reported.Methods: We first analysed the expression of DLEU2 across cancers and the correlation between DLEU2 and the clinical features of KIRC and LIHC by using the “ggplot2” package in R and searched the Oncomine database and Timer website platform. We verified the expression of DLEU2 in the GEO dataset (GSE105261 and GSE45267). Receiver operating characteristic (ROC) curves were drawn using the “pROC” and “ggplot2” packages in R, and we constructed a DLEU2-based prognostic nomogram for KIRC and LIHC by using the “survival” and “rms” packages in R. Then, we analysed the correlation between DLEU2 expression and prognosis in R as well as the correlation between DLEU2 and immune cell infiltration in the TIMER database. Finally, we explored the causes of DLEU2 upregulation in the UCSC Xena and UALCAN databases.Results: We found that DLEU2 was upregulated in many cancers, including KIRC and LIHC. Expression of DLEU2 is associated with tumour stage, grade, lymphatic metastasis, and distant metastasis in KIRC as well as alpha-fetoprotein (AFP), tumour stage, grade, lymphatic metastasis, and distant metastasis in LIHC. DLEU2 is an adverse factor for the prognosis of KIRC and LIHC. In addition, DLEU2 has moderate accuracy in diagnosing KIRC and LIHC and predicting their prognosis. Moreover, we found that expression of DLEU2 correlated positively with immune cell infiltration in KIRC and LIHC, and upregulation of DLEU2 in KIRC and LIHC suggests a poor prognosis based on immune cells analysis. Genetic and epigenetic analyses of DLEU2 indicate that copy number variations (CNVs) and methylation contribute to the upregulation of DLEU2.Conclusion: The long noncoding RNA DLEU2 has the potential to predict the prognosis and immune infiltration of KIRC and LIHC.Keywords: DLEU2, prognosis, immune infiltration, KIRC, LIHC

Yuhui Ruan,1 Weisin Chen,2 Chenyang Zhuang,2 Hong Lin2,3 1School of International and Public Affairs, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Institute of Medical Science Popularization, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hong LinDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaTel +86 13636526656Email lin.hong1@zs-hospital.sh.cnPurpose: This study aimed to elucidate the quality of life of older adults/patients with degenerative lumbar diseases (ODLs) and analyse its association with some of their health-related perceptions.Materials and Methods: This mixed-methods study consisted of a questionnaire survey and an in-depth interview, which was designed within this study. ODLs were recruited from January 12, 2017 to June 27, 2018. The independent sample t-test and grounded theory coding method were employed for data analysis.Results: Of the 125 participants who returned valid questionnaires, 18 were included in the in-depth interviews. ODLs’ quality of life was associated with the following health-related perceptions: “life barriers”, “subjective health status”, and “treatment outcomes” across the domains of physiology, psychology, social relations, and environment.Conclusion: Our findings indicate that ODLs’ quality of life is associated with their health-related perceptions. Thus, to improve older adults’ quality of life, more attention should be paid to enhancing non-medical factors such as their health-related perceptions.Keywords: life barriers, subjective health status, treatment outcomes

Zixiang Wang,1,* Chenyang Zhuang,1,* Weixin Chen,1 Zefang Li,2 Juan Li,1,3 Hong Lin,1,3 Dong Jian1 1Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Orthopedics, Qianjiang Central Hospital of Chongqing, Chongqing, 409000, People’s Republic of China; 3Department of Orthopedics, Shanghai Geriatrics Medical Center, Fudan University, Shanghai, 201100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Lin; Dong JianDepartment of Orthopedics, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, 200032, People’s Republic of ChinaTel +86-13636526656; +86-13916930859Email lin.hong1@zs-hospital.sh.cn; dong.jian@zs-hospital.sh.cnPurpose: The research aimed to compare the therapeutic effect of teriparatide (TPTD) and zoledronic acid (ZOL) therapy on bone formation and spinal fusion in patients with osteoporosis (OP) who underwent transforaminal lumbar interbody fusion (TLIF).Methods: On the basis of different anti-OP treatment options, the TPTD group was treated daily with TPTD (20 μg. ih. qd) for at least 6 months, while the ZOL group was treated with a single dose of ZOL (5 mg. ivgtt. st) postoperatively. The visual analogue scale (VAS), Oswestry Disability Index (ODI), bone mineral density (BMD), and concentration of bone turnover markers before, 6, and 12 months after surgery were evaluated. X-ray and three-dimensional computed tomography scans were performed at 6 and 12 months postoperatively to assess interbody fusion.Results: The number of patients in the TPTD and ZOL groups was 29 and 38 patients, respectively. The VAS and ODI scores in both groups were significantly reduced at 6 and 12 months after TLIF. Compared with that of baseline, the lumbar spine BMD of TPTD patients increased significantly from 0.716± 0.137 g/cm2 to 0.745± 0.124 g/cm2 and 0.795± 0.123 g/cm2 at 6 and 12 months, respectively, and was significantly higher than that of the ZOL group at 12 months (0.720± 0.128 g/cm2). The bone formation marker, P1NP, in the TPTD group increased significantly (145.48± 66.64 ng/mL and 119.55± 88.27 ng/mL) compared with baseline (44.67± 25.15 ng/mL) and in the ZOL group (28.82± 19.76 ng/mL and 29.94± 20.67 ng/mL) at 6 and 12 months, respectively. The fusion rates in the TPTD and ZOL groups were 57% and 45% at 6 months, without statistical significance. However, TPTD had a more statistically significant positive influence on fusion rate than ZOL at 12 months (86% vs 70%).Conclusion: TPTD was more efficient than ZOL in bone formation and spinal fusion in OP patients who underwent TLIF.Keywords: teriparatide, zoledronic acid, osteoporosis, TLIF

Chenyang Zhuang,1,&ast; Zixiang Wang,1,&ast; Weisin Chen,1 Bo Tian,1 Juan Li,1,2 Hong Lin1,2 1Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Orthopedics, Shanghai Geriatrics Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan LiDepartment of Orthopedics, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86 21 6404 1990Email li_juan1983@outlook.comHong LinDepartment of Orthopedics, Shanghai Geriatrics Center, Fudan University, No. 2560 Chunshen Road, Shanghai, 201104, People’s Republic of ChinaEmail lin.hong1@zs-hospital.sh.cnPurpose: Osteoporosis and endplate damage, two primary orthopedic disorders that have adverse effects on the quality of life of older adults, may have some previously unknown relationship. The purpose of this study was to determine the potential association between osteoporosis and endplate damage with two specific imaging scoring systems and analyze the underlying mechanisms.Patients and Methods: A cross-sectional study including 156 patients with degenerative disc disease (DDD) who visited our department in 2018 was performed. Data including age, sex, body mass index, Hounsfield unit (HU) values utilizing computed tomography (CT), and total endplate scores (TEPSs) using magnetic resonance imaging (MRI) of all patients were retrospectively collected and analyzed. The average HU value and TEPS of L1–L4 were used to represent the degrees of bone mineral density (BMD) and endplate damage, respectively. Patients with an HU value < 110 were defined as having osteoporosis and placed in the low-BMD group; otherwise, they were placed in the normal-BMD group. Multivariate logistic regression models were used to determine the independent factors of endplate damage.Results: The TEPSs in the low-BMD group were significantly higher (6.4 ± 1.6 vs 5.0 ± 0.9, p < 0.001) overall and in every segment of L1–L4 (p < 0.01). A significant negative correlation was found between TEPS and HU values (p < 0.001). The HU value (odds ratio [OR] 0.221; 95% confidence interval [CI], 0.148– 0.295, p < 0.001), age (OR 0.047; 95% CI, 0.029– 0.224, p < 0.001), and BMD (OR 3.796; 95% CI, 2.11– 7.382, p < 0.05) were independent factors influencing endplate damage.Conclusion: A significantly positive correlation was observed between osteoporosis and endplate damage, indicating the requirement for a more comprehensive therapeutic regimen for treating patients with DDD complicated with osteoporosis.Keywords: degenerative disc diseases, bone mineral density, computed tomography, magnetic resonance imaging

Xiaonan Xu, 1,* Chengle Zhuang, 2,* Liming Chen 1 1Department of Neurology, Shenzhen University General Hospital, Shenzhen 518000, Guangdong Province, People’s Republic of China; 2Department of Urology, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liming Chen Email limingchen_2000@sina.comBackground: Acute minor stroke (AMS) is one kind of hypoxic ischemic necrosis with no more than 4 National Institutes of Health Stroke Scale (NIHSS) score. However, the early diagnosis of AMS is tough for lack of effective molecular markers. Recently, many long non-coding RNAs (lncRNAs) associated with AMS have been gradually revealed. Here, we aim to find the potential biomarkers of lncRNAs in exosomes isolated from blood serum of patients with AMS for early detection.Methods: RNA-seq technique, KEGG pathway analysis and GO enrichment analysis were used in this study. Besides, reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate expression levels of four of eleven differentially expressed lncRNAs (lnc-CRKL-2, lnc-NTRK3-4, RPS6KA2-AS1 and lnc-CALM1-7) involved in the neurotrophin signaling pathway.Results: The expression levels of lnc-CRKL-2 (mean value 48, standard deviation 4.583, P = 0.003) and lnc-NTRK3-4 (mean value 32.3, standard deviation 2.08, P = 0.001) were increased significantly in AMS patients, while the expression levels of RPS6KA2-AS1 (mean value − 118.7, standard deviation 7.09, P = 0.001) and lnc-CALM1-7 (mean value − 148.7, standard deviation 6.10, P = 0.001) were decreased dramatically.Conclusion: In conclusion, these four new revealed lncRNAs may be used as novel joint biomarkers for the early detection of AMS.Keywords: exosomes, stroke, LncRNAs, biomarker

Zhe Fan,1,2,* Yue Zhao,3,* Shuang Wang,3 Feng Zhang,4 Chengjun Zhuang51Department of General Surgery, The Third People’s Hospital of Dalian, Dalian Medical University, Dalian, People’s Republic of China; 2Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Graduate School, Dalian Medical University, Dalian, People’s Republic of China; 4Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 5Department of Critical Care Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China*These authors contributed equally to this workBackground: Tetanus is a serious disease resulting in muscle spasm, and even death.Methods: A retrospective, single-center study was conducted by analyzing demographic and clinical parameters.Results: The study included 12 males (70.6%) and 5 females (29.4%). The mean age of the patients was 56.71±9.05 years. Patient occupations included farming (47.0%), retired (23.5), homebound (23.5), and workers (6.0%). The causes of patient injuries were as follows: metal injury (52.9%), deep injury (29.4%), electrical injury (5.9%), maxillofacial region and knee injury (5.9%), and skin ulceration (5.9%). The disease duration ranged from 3 to 36 days, and the mean incubation period was 12.65±10.17 days. Four patients had co-morbidities. The infected patients were given tetanus antitoxin (TAT) and antibiotics treatment. One patient was given continuous renal replacement therapy (CRRT) and only one patient died.Conclusions: In our department, although tetanus is a serious disease, with effective treatment, patients have reasonable cure and low death rates.Keywords: tetanus, intensive care unit, retrospective study

Chunbo Zhuang,1 Lei Zheng,1 Pei Wang2 1Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Background: Long non-coding RNAs (LncRNAs) play important roles in tumorigenesis and progression. Recent studies have demonstrated that LncRNA HNF1A antisense RNA 1 (HNF1A-AS1) is aberrantly expressed in several types of cancers and is associated with poor outcomes. This meta-analysis was conducted to investigate the relationship between HNF1A-AS1 expression and clinical outcomes in cancer patients. Methods: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang databases (updated until December 31, 2017) for literature. A total of eight studies with 789 cancer patients were finally included in the present meta-analysis. Results: The results showed that high expression of HNF1A-AS1 significantly predicted poor overall survival (HR=3.10, 95% CI: 1.58–6.11, P=0.001), which was further validated using The Cancer Genome Atlas (TCGA) dataset. Moreover, high HNF1A-AS1 expression was also associated with advanced TNM stage (OR=3.32, 95% CI: 2.28–4.83, P

Increasing roof albedo (using a “cool” roof) and night ventilation are passive cooling technologies that can reduce the cooling loads in buildings, but existing studies have not comprehensively explored the potential benefits of integrating these two technologies. This study combines an experiment in the summer and transition seasons with an annual simulation so as to evaluate the thermal performance, energy savings and thermal comfort improvement that could be obtained by coupling a cool roof with night ventilation. A holistic approach integrating sensitivity analysis and multi-objective optimization is developed to explore key design parameters (roof albedo, night ventilation air change rate, roof insulation level and internal thermal mass level) and optimal design options for the combined application of the cool roof and night ventilation. The proposed approach is validated and demonstrated through studies on a six-storey office building in Xiamen, a cooling-dominated city in southeast China. Simulations show that combining a cool roof with night ventilation can significantly decrease the annual cooling energy consumption by 27% compared to using a black roof without night ventilation and by 13% compared to using a cool roof without night ventilation. Roof albedo is the most influential parameter for both building energy performance and indoor thermal comfort. Optimal use of the cool roof and night ventilation can reduce the annual cooling energy use by 28% during occupied hours when air-conditioners are on and reduce the uncomfortable time slightly during occupied hours when air-conditioners are off.

Roofs with high-reflectance (solar reflectance) coating, commonly known as cool roofs, can stay cool in the sun, thereby reducing building energy consumption and mitigating the urban heat island. However, chemical-physical degradation and biological growth can decrease their solar reflectance and the ability to save energy. In this study, the solar spectral reflectance of 12 different roofing products with an initial albedo of 0.56–0.90 was measured before exposure and once every three months over 32 months. Specimens were exposed on the roofs of dormitory buildings in Xiamen and Chengdu, each major urban areas with hot summers. The albedos of high and medium-lightness coatings stabilized in the ranges 0.45–0.62 and 0.36–0.59 in both cities, respectively. This study yielded albedo loss exceeded those reported in the latest Chinese standard by 0.08–0.15. Finally, DesignBuilder (EnergyPlus) simulations estimate that a new cool roof with albedo 0.78 on a six-story dormitory building will yield annual site energy savings (heating and cooling) for the top floor, which are 8.01 kWh/m2 (24.2%) and 9.12 kWh/m2 (26.3%) per unit floor area in Xiamen and Chengdu, respectively; while an aged cool roof with albedo 0.45 and 0.56 will yield the annual savings by 5.12 kWh/m2 (15.4%) and 2.47 kWh/m2 (10.5%) in these two cities.

Abstract Background Traumatic pulmonary pseudocyst is a rare “cystlike” lung lesion that typically develops following blunt chest trauma. It differs from lung cancer associated with cystic airspaces in terms of pathogenic mechanisms, clinical manifestations, and radiological features. Furthermore, there are few reports of the diagnostic bias between traumatic pulmonary pseudocyst and lung cancer associated with cystic airspaces. Here, we present a rare case of lung cancer associated with cystic airspaces that mimicks traumatic pulmonary pseudocyst. Case presentation A 61-year-old man with no chest medical or surgical history, no chest radiologic examination within the last five years, and no smoking history had an air-filled “cystlike” lesion surrounded by solid components and ground-glass opacities in the middle third of the right upper lobe of the lung during a computed tomography evaluation following blunt chest trauma. He was initially diagnosed with traumatic pulmonary pseudocyst and treated conservatively. On the third post-trauma day, he experienced hemoptysis, which was successfully treated with intravenous hemostatic medication. On the ninth post-trauma day, he exhibited a significant hemoptysis and a moderate dyspnea. A subsequent chest computed tomography scan demonstrated that the solid components had entered the lesion’s cavity and significantly expanded, and the surrounding ground-glass opacities had slightly enlarged. A contrast-enhanced chest computed tomography scan and a three-dimensional reconstruction computed tomography image confirmed that the solid components were a hematoma caused by damage to the right upper pulmonary vein. A right upper lobectomy was performed based on the concern about severe intrapulmonary bleeding. An intraoperative frozen section analysis showed significant bleeding in the lung parenchyma. Adenosquamous carcinoma was unexpectedly identified during the postoperative pathological examination of the resected specimen. A diagnosis of primary lung adenosquamous carcinoma was made. He was discharged on the seventh postoperative day and followed up for two years without any recurrence. Conclusions The potential of lung cancer associated with cystic airspaces should be considered for “cystlike” lung lesions discovered in elderly patients after blunt chest trauma. A comprehensive review of the medical history, meticulous analysis of the radiological findings, and close monitoring can help clinicians reduce the risk of diagnostic bias.

Abstract Background Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. Methods Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. Results We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP (aOR = 2.999, 95% CI: 1.886–4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP (aOR = 0.307, 95% CI: 0.194–0.485) and those using both daily and on-demand PrEP (aOR = 0.114, 95% CI: 0.058–0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. Conclusions The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.

Abstract Background Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. Methods Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. Results The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0–21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. Conclusions Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases.

Abstract Introduction Few studies focused on the Pre-Exposure Prophylaxis (PrEP) -related aspects, and the applicability of prior evidence to young men who have sex with men (YMSM) students was unknown. This study aimed to assess the awareness, willingness, uptake, and adherence (AWUA) to PrEP among YMSM students in China and to explore the associated factors with these stages. Methods A cross-sectional survey with a sizable sample of 1151 was conducted among YMSM students aged 16 and above, who self-identified as men who have sex with men(MSM) and resided in mainland China between October 20 and December 20, 2021. The chi-square test and Fisher’s exact test were used for univariate analysis, followed by multivariable logistic regression analysis of influencing factors at all levels. Results According to the cascade analysis approach, 88.71% of the participants were aware of PrEP, among which 66.7% expressed willingness to use it. Among those who were willing to use PrEP, only 13.80% took it, and of those who took it, 44.68% adhered to it. The students taking PrEP were those with higher education (OR = 4.239, 95% CI: 1.334–13.467), residence in pilot cities (OR = 2.791, 95% CI: 1.498–5.198), residence in high-risk areas (OR = 5.082, 95% CI: 2.224–11.612), engagement in multi-person sexual behavior (OR = 2.186, 95% CI: 1.236–3.867), and substance use (OR = 1.908, 95% CI: 1.167–3.118). Furtherly, students with higher adherence to PrEP were likely to have receptive sexual behaviors (OR = 8.702, 95% CI: 2.070-36.592), absence of substance use (OR = 4.468, 95% CI: 1.371–14.561), and uptake of PrEP through daily oral route. (OR = 7.065, 95% CI: 1.699–29.371). Conclusion YMSM students exhibit distinct patterns of “high awareness, low willingness, low uptake, and low adherence” to PrEP. Strategies for reduction in the acquisition of HIV prioritizing the current features of utilizing PrEP were urgently warranted.

Abstract Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age‐related osteoarthritis (OA). In the present study, highly lubricated and drug‐loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)‐modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti‐chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA‐seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO‐/P53 pathway. Notably, the intra‐articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age‐related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

BackgroundThe association of Remnant cholesterol (RC) with renal function and its progression in patients with Type 2 diabetes (T2DM) related chronic kidney disease (CKD) remains unclear.Methods8,678 patients with T2DM-related CKD were included in cross-sectional analysis, and 6,165 patients were enrolled in longitudinal analysis and followed up for a median of 36.0 months. The outcomes were renal composite endpoint event and rapid progression of renal function.Results24.54% developed a renal composite endpoint event, and 27.64% rapid progression of renal function. RC levels above 0.56 mmol/L independently increased the risk of both renal composite endpoint (HR, 1.17; 95% CIs, 1.03-1.33) and rapid progression of renal function (OR, 1.17; 95% CIs, 1.01- 1.37). TG levels above 1.65 mmol/L only increased the risk of renal composite endpoint (HR, 1.16; 95% CIs, 1.02 -1.32). TC levels above 5.21 mmol/L increased the risk of renal composite endpoint (HR, 1.14; 95% CIs, 1.01-1.29) only in patients with proteinuria≥0.5g/d. Conversely, HDL-C levels below 1.20 mmol/L or above 1.84 mmol/L increased the risk of rapid progression of renal function (OR, 0.88; 95% CIs, 0.70 -0.99) in patients with proteinuria

Pentatricopeptide repeat (PPR) proteins represent one of the largest protein families in plants and typically localize to organelles like mitochondria and chloroplasts. By contrast, CYTOPLASM- LOCALIZED PPR1 (OsCPPR1) is a cytoplasm-localized PPR protein that can degrade OsGOLDEN- LIKE1 (OsGLK1) mRNA in the tapetum of rice anther. However, the mechanism, by which OsCPPR1 recognizes and binds to OsGLK1 transcripts, remains unknown. Through protein structure prediction and macromolecular docking experiments, we observed that distinct PPR motif structures of OsCPPR1 exhibited varying binding efficiencies to OsGLK1 RNA. Moreover, RNA-electrophoretic mobility shift assay experiment demonstrated that the recombinant OsCPPR1 can directly recognize and bind to OsGLK1 mRNA in vitro. This further confirmed that the mutations in the conserved amino acids in each PPR motif resulted in loss of activity, while truncation of OsCPPR1 decreased its binding efficiency. These findings collectively suggest that it may require some co-factors to assist in cleavage, a facet that warrants further exploration in subsequent studies.

Abstract Background Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. Methods PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. Results BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. Conclusion Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling.

A pre-metastatic niche (PMN) is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic organs. Extracellular vesicles (EVs) play a role in intercellular communication by delivering cargoes, such as noncoding RNAs (ncRNAs). The pivotal role of extracellular vesicle-derived noncoding RNAs (EV-ncRNAs) in the PMN has attracted increasing attention. In this review, we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression, vascular permeability and angiogenesis, inflammation, metabolic reprogramming, and fibroblast alterations. In particular, we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different cancers. Finally, we discussed the promising clinical applications of EV-ncRNAs, including their potential as diagnostic and prognostic markers and therapeutic targets.

Objectives Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high incidence and mortality rates worldwide. This study aimed to investigate the correlation between LINC-PINT polymorphisms and ESCC risk in the Hainan Han population.Methods A total of 391 patients with ESCC and 452 healthy controls were enrolled to evaluate the effect of LINC-PINT SNPs (single nucleotide polymorphisms) on ESCC susceptibility. Associations were evaluated by calculating odds ratios (OR) and 95% confidence intervals (CIs). Multifactor dimensionality reduction analysis was performed to explore the association between SNP-SNP interactions and ESCC susceptibility. We further determined the correlation between clinical indicators and SNP in patients with ESCC.Results Our study showed that rs157916 (OR 0.63, p = 0.011) and rs157928 (OR 0.80, p = 0.021) were associated with a decreased risk of ESCC. Stratified analysis indicated that rs157916 could decrease the risk of ESCC in people aged >64 years, in males, and non-drinkers (OR 0.58, p = 0.042; OR 0.58, p = 0.010; OR 0.62, p = 0.025, respectively). Rs16873842 was related to a decreased risk of ESCC in males (OR 0.70, p = 0.015). Rs7801029 was associated with ESCC risk in females (OR 0.39, p = 0.033) and non-drinkers (OR 0.68, p = 0.040). Rs7781295 decreased the ESCC risk in smokers (OR 0.58, p = 0.046) and drinkers (OR 0.58, p = 0.046). In addition, rs157928 played a protective role in ESCC risk in females (OR 0.39, p = 0.033) and non-smokers (OR 0.32, p = 0.006). Additionally, the best predictive model for ESCC was a combination of rs157916, rs16873842, rs7801029, rs7781295, rs28662387, and rs157928.Conclusion Our study revealed that LINC-PINT polymorphisms were associated with ESCC risk.

Men who have sex with men (MSM) are at a high risk of HIV infection and should be offered effective preventive measures, such as pre-exposure prophylaxis (PrEP). However, PrEP uptake among eligible MSM was not as high as desired. Diverse research findings on how risky sexual behaviors affect PrEP uptake highlight the necessity for a comprehensive investigation. Understanding the interconnectedness of different sexual behaviors is crucial for evaluating their impact on PrEP uptake among eligible MSM.Using a proportional sampling method, we recruited 5877 MSM aged 16 years and above in mainland China according to PrEP eligibility criteria. Through latent class analysis (LCA), three distinct sexual behavior patterns were identified among eligible MSM. Demographic variances and PrEP uptake among the three distinct sexual behavior patterns were examined using chi-squared tests and multinomial logistic regression.LCA revealed three patterns: low-risk (4,815 MSM), medium-risk (516 MSM), and high-risk (546 MSM). MSM aged 25 years or older with a monthly income of ≥¥8,000 were more likely to be in the medium-risk group. Those from areas with high HIV prevalence and engaging as ''top'' in anal sex were more likely to be in the medium- and high-risk groups. The medium- and high-risk groups had a higher willingness, uptake, and adherence rates for PrEP than the low-risk group.LCA is effective in identifying diverse sexual behavior patterns among MSM, aiding targeted interventions to enhance PrEP uptake. Addressing demographic variations and tailoring interventions for specific risk groups are crucial for promoting PrEP dissemination and reducing HIV infection risk in eligible MSM.

Abstract Background Colorectal cancer (CRC) is one of the most common malignant tumors, influenced by several genetic loci in its clinical phenotypes. The aim of this study was to determine the relationship between the MMP8 gene polymorphism and CRC risk in the Chinese Han population. Method This study recruited 688 CRC patients and 690 healthy controls. The relationship between MMP8 polymorphism and CRC susceptibility was assessed by calculating the odds ratio (OR) and 95% confidence interval (CI) after stratifying by age, gender, body mass index (BMI), smoking, and alcohol consumption under a multi-genetic model. Results MMP8 rs3740938 was associated with increased CRC predisposition (p = 0.016, OR = 1.24, 95% CI: 1.04–1.48), and this association was detected particularly in subjects aged > 60 years, females, people with BMI > 24 kg/m2, smokers, and drinkers. Moreover, rs3740938 was found to be associated with the pathological type of rectal cancer. Conclusions Our results first displayed that rs3740938 in MMP8 was a risk factor for CRC predisposition. This finding may provide a new biological perspective for understanding the role of the MMP8 gene in CRC pathogenesis.

Maintaining the confidentiality and integrity of the messages during a transmission is one of the most important aims of encrypted communication systems. Many achievements were made using biomolecules to improve the quality of the messages in communication. At the same time, it is still a challenge to construct cooperative communications based on the interactions between biomolecules to achieve the confidentiality and integrity of the transmitted messages. DNA-based encrypted communications have been developed, and in particular, DNA-origami-based message encryption can combine steganography and pattern encryption and exhibits extremely high confidentiality. Nevertheless, limited by biological characteristics, encrypted messages based on DNA require a strict storage environment in the process of transmission. The integrity of the message encoded in the DNA may be damaged when the DNA is in an unfriendly and hard environment. Therefore, it is particularly significant to improve the stability of DNA when it is exposed to a harsh environment during transmission. Here, we encoded the information into the DNA strands that were condensed for encryption to form a nanosphere covered with a shell of SiO2, which brings high-density messages and exhibits higher stability than separated DNA. The solid shell of SiO2 could prevent DNA from contacting the harsh environment, thereby protecting the DNA structure and maintaining the integrity of the information. At the same time, DNA nanospheres can achieve high throughput input and higher storage density per unit volume, which contribute to confusing the message strand (M-strand) with the interference strand in the stored information. Condensing DNA into the nanosphere that is used for DNA origami cryptography has the potential to be used in harsh conditions with higher confidentiality and integrity for the transmitted messages.

Abstract The commercial space industry seems to draw worldwide attention in the recent two decades to respond to the increasingly broad market demand. Compared with Western countries, the development of China’s commercial space industry is still in its infancy and faces many daunting challenges. Few studies have considered the dual perspective of government and market of commercial space industry in China. Aiming at exploring the influencing factors and future directions of the development of China’s commercial space industry, this paper proposed the theoretical analysis framework consisting of Policy, Innovation and Economics, and conducted a synergistic analysis of government and market in China’s commercial space industry. Specifically, based on the interview data, assisted by a machine learning approach, we have conducted an industry analysis of the influencing factors of commercial space in China. The results show that China’s commercial space industry is rapidly developing with many characteristics. Specifically, at present, there is a lack of specific and operational policies at the implementation level. Despite limited disruptive innovation, commercial space companies have achieved breakthroughs in many key areas. The overall industry is exploring more stable and sustainable profit models. The findings of this study contribute to the topic of industry development in business management literature by underpinning the policy discussion, technological analysis and direction for the future development of China’s commercial space industry. The industry practitioners may also benefit from the practices that were discussed in this research.

Discrete element method (DEM) has been widely utilised to model the mechanical behaviours of granular materials. However, with simplified particle morphology or rheology-based rolling resistance models, DEM failed to describe some responses, such as the particle kinematics at the grain-scale and the principal stress ratio against axial strain at the macro-scale. This paper adopts a computed tomography (CT)-based DEM technique, including particle morphology data acquisition from micro-CT (μCT), spherical harmonic-based principal component analysis (SH-PCA)-based particle morphology reconstruction and DEM simulations, to investigate the capability of DEM with realistic particle morphology for modelling granular soils' micro-macro mechanical responses with a consideration of the initial packing state, the morphological gene mutation degree, and the confining stress condition. It is found that DEM with realistic particle morphology can reasonably reproduce granular materials’ micro-macro mechanical behaviours, including the deviatoric stress–volumetric strain–axial strain response, critical state behaviour, particle kinematics, and shear band evolution. Meanwhile, the role of multiscale particle morphology in granular soils depends on the initial packing state and the confining stress condition. For the same granular soils, rougher particle surfaces with a denser initial packing state and a higher confining stress condition result in a higher degree of shear strain localisation.

Objectives To assess the association between ambient temperature and diurnal temperature range (DTR) on emergency admissions for hyperventilation syndrome (HVS).Design Distributed lag non-linear model design was used with a lag time to 5 days.Setting Emergency admission data used were from the Beijing Red Cross Emergency Centre (2017–2018).Participants and exposure Cases were those with emergency visits to the Beijing Emergency Center during the period 2017–2018 and who were given the primary outcome indicator defined as HVS according to the International Classification of Diseases, 10th edition code F45.303. Ambient temperature and DTR were used as exposure factors with adjustments for relative humidity, wind speed, precipitation, seasonality long-term trend and day of the week.Main outcome measure We used the minimum emergency visits temperature as a reference to indicate the relative risk with 95% CI of exposure–response for the risk of HVS visits at different temperatures.Results A u-shape was described between ambient temperature and HVS visits, with a minimum risk at 12°C. Moderate heat (23°C) at lag (0–3) days, extreme heat at lag 0 days, had greatest relative risks on HVS visits, with 2.021 (95% CI 1.101 to 3.71) and 1.995 (95% CI 1.016 to 3.915), respectively. A stronger association between HVS visits and temperature was found in women and aged ≤44 years. Notably, the relationship between DTR and HVS visits appeared a reverse u-shaped. Low DTR (4°C) effect appeared at lag (0–1) days with 0.589 (95% CI 0.395 to 0.878), lasting until lag (0–3) days with 0.535 (95% CI 0.319 to 0.897) and was associated with a reduced risk of HVS visits in women and those aged ≤44 years.Conclusions Ambient temperature and DTR were associated with HVS visits, appearing a differentiation in gender and age groups. Timely prevention strategies during high temperatures and control mild changes in temperature might reduce the risk of HVS.

Summary: Immune escape is identified as one of the reasons for the poor prognosis of colorectal cancer (CRC) patients. Circular RNAs are considered to promote tumor progression by mediating tumor immune escape. We discovered that higher expression of circYAP1 was associated with a worse prognosis of CRC patients. Functional experiments in vitro and in vivo showed that circYAP1 upregulation inhibited the cytotoxicity of CD8+ T cells by upregulating programmed death ligand-1 (PD-L1). Mechanistically, we found that circYAP1 directly binds to the YAP1 protein to prevent its phosphorylation, enhancing proportion of YAP1 protein in the nucleus, and that YAP1 interacts with TCF4 to target the PD-L1 promoter and initiate PD-L1 transcription in CRC cells. Taken together, circYAP1 promotes CRC immune escape and tumor progression by activating the YAP1/TCF4-PD-L1 axis and may provide a new strategy for combination immunotherapy of CRC patients.

Abstract In mice, retrotransposon‐associated long noncoding RNAs (lncRNA) play important regulatory roles in pre‐implantation development; however, it is largely unknown whether they function in the pre‐implantation development in pigs. The current study aims to screen for retrotransposon‐associated lncRNA in porcine early embryos and identifies a porcine 8‐cell embryo‐specific SINE‐associated nuclear long noncoding RNA named SAWPA. SAWPA is essential for porcine embryonic development as depletion of SAWPA results in a developmental arrest at the 8‐cell stage, accompanied by the inhibition of the JNK‐MAPK signaling pathway. Mechanistically, SAWPA works in trans as a transcription factor for JNK through the formation of an RNA‐protein complex with HNRNPA1 and MED8 binding the SINE elements upstream of JNK. Therefore, as the first functional SINE‐associated long noncoding RNAs in pigs, SAWPA provides novel insights for the mechanism research on retrotransposons in mammalian pre‐implantation development.