Associations of low-density lipoprotein cholesterol with all-cause and cause-specific mortality in older adults in China.

CONTEXT: Limited information was available on detailed associations of low-density lipoprotein cholesterol (LDL-C) with all-cause and cause-specific mortality in older adults. METHODS: This prospective cohort study included a representative sample of 211,290 adults aged 65 or older, who participated in Shenzhen Healthy Aging Research 2018-2019. The vital status of the participants by 31 December, 2021 was determined. We estimated the hazard ratios (HR) with 95% confidence intervals for all-cause or cause-specific mortality using multivariable Cox proportional hazards models and Cox models with restricted cubic spline(RCS) . RESULTS: The median follow-up time was 3.08 years. A total of 5,333 participants were confirmed to have died. Among them, 2,303 cardiovascular disease (CVD) deaths and 1,881 cancer deaths occurred. Compared to those with LDL-C of 100-129 mg/dL, the all-cause mortality risk was significantly higher for individuals with LDL-C level that was very low (< 70 mg/dL) or low (70-99 mg/dL). Compared with individuals with the reference LDL-C level, the multivariable-adjusted HR for CVD-specific mortality was 1.327 for those with very low LDL-C level (< 70 mg/dL), 1.437 for those with high LDL-C level (160 mg/dL ≦ LDL-C < 190mg/dL), 1.528 for those with very high LDL-C level (≥ 190 mg/dL). Low LDL-C level (70-99 mg/dL) and very low LDL-C level (< 70 mg/dL) were also associated with increased cancer mortality and other-cause mortality, respectively. The results from RCS curve showed similar results. CONCLUSION: Considering the risk of all-causes mortality and cause-specific mortality, we recommended 100-159 mg/dL as the optimal range of LDL-C among older adults in China.

Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles.

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.

Sociodemographic and lifestyle determinants of multimorbidity among community-dwelling older adults: findings from 346,760 SHARE participants.

BACKGROUND: This study aimed to investigate the prevalence of multimorbidity and its associated factors among the older population in China to propose policy recommendations for the management of chronic diseases in older adults. METHODS: This study was conducted based on the 2021 Shenzhen Healthy Ageing Research (SHARE), and involved analysis of 346,760 participants aged 65 or older. Multimorbidity is defined as the presence of two or more clinically diagnosed or non self-reported chronic diseases among the eight chronic diseases surveyed in an individual. The Logistic analysis was adopted to explore the potential associated factors of multimorbidity. RESULTS: The prevalences of obesity, hypertension, diabetes, anemia, chronic kidney disease, hyperuricemia, dyslipidemia and fatty liver disease were 10.41%, 62.09%, 24.21%, 12.78%, 6.14%, 20.52%, 44.32%, and 33.25%, respectively. The prevalence of multimorbidity was 63.46%. The mean count of chronic diseases per participant was 2.14. Logistic regression indicated that gender, age, marriage status, lifestyle (smoking status, drinking status, and physical activity), and socioeconomic status (household registration, education level, payment method of medical expenses) were the common predictors of multimorbidity for older adults, among which, being women, married, or engaged in physical activity was found to be a relative determinant as a protective factor for multimorbidity after the other covariates were controlled. CONCLUSION: Multimorbidity is prevalent among older adults in Chinese. Guideline development, clinical management,and public intervention should target a group of diseases instead of a single condition.

PEGylated pH-responsive peptide-mRNA nano self-assemblies enhance the pulmonary delivery efficiency and safety of aerosolized mRNA.

Inhalable messenger RNA (mRNA) has demonstrated great potential in therapy and vaccine development to confront various lung diseases. However, few gene vectors could overcome the airway mucus and intracellular barriers for successful pulmonary mRNA delivery. Apart from the low pulmonary gene delivery efficiency, nonnegligible toxicity is another common problem that impedes the clinical application of many non-viral vectors. PEGylated cationic peptide-based mRNA delivery vector is a prospective approach to enhance the pulmonary delivery efficacy and safety of aerosolized mRNA by oral inhalation administration. In this study, different lengths of hydrophilic PEG chains were covalently linked to an amphiphilic, water-soluble pH-responsive peptide, and the peptide/mRNA nano self-assemblies were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro mRNA binding and release, cellular uptake, transfection, and cytotoxicity were studied, and finally, a proper PEGylated peptide with enhanced pulmonary mRNA delivery efficiency and improved safety in mice was identified. These results showed that a proper N-terminus PEGylation strategy using 12-monomer linear monodisperse PEG could significantly improve the mRNA transfection efficiency and biocompatibility of the non-PEGylated cationic peptide carrier, while a longer PEG chain modification adversely decreased the cellular uptake and transfection on A549 and HepG2 cells, emphasizing the importance of a proper PEG chain length selection. Moreover, the optimized PEGylated peptide showed a significantly enhanced mRNA pulmonary delivery efficiency and ameliorated safety profiles over the non-PEGylated peptide and LipofectamineTM 2000 in mice. Our results reveal that the PEGylated peptide could be a promising mRNA delivery vector candidate for inhaled mRNA vaccines and therapeutic applications for the prevention and treatment of different respiratory diseases in the future.

Reduction in Nuclear Size by DHRS7 in Prostate Cancer Cells and by Estradiol Propionate in DHRS7-Depleted Cells.

Increased nuclear size correlates with lower survival rates and higher grades for prostate cancer. The short-chain dehydrogenase/reductase (SDR) family member DHRS7 was suggested as a biomarker for use in prostate cancer grading because it is largely lost in higher-grade tumors. Here, we found that reduction in DHRS7 from the LNCaP prostate cancer cell line with normally high levels of DHRS7 increases nuclear size, potentially explaining the nuclear size increase observed in higher-grade prostate tumors where it is lost. An exogenous expression of DHRS7 in the PC3 prostate cancer cell line with normally low DHRS7 levels correspondingly decreases nuclear size. We separately tested 80 compounds from the Microsource Spectrum library for their ability to restore normal smaller nuclear size to PC3 cells, finding that estradiol propionate had the same effect as the re-expression of DHRS7 in PC3 cells. However, the drug had no effect on LNCaP cells or PC3 cells re-expressing DHRS7. We speculate that separately reported beneficial effects of estrogens in androgen-independent prostate cancer may only occur with the loss of DHRS7/ increased nuclear size, and thus propose DHRS7 levels and nuclear size as potential biomarkers for the likely effectiveness of estrogen-based treatments.

The percutaneous oval forceps suture-guiding method with anchor nails for Achilles tendon repair.

BACKGROUND: Acute Achilles tendon rupture (AATR) is a common injury of the foot and ankle. So far, the optimal management of AATR remains controversial. The target of the present retrospective study was to describe a new operative technique for percutaneous repair of AATR and evaluate efficacy of the technique. METHODS: In the present study, 32 patients were enrolled with AATR treated with the percutaneous oval forceps suture-guiding method with anchor nails from Jan 2014 to Jan 2017. The operation duration and length of incision were collected. The functional outcomes were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) score, Achilles tendon total rupture score (ATRS), range of motion (ROM) of the ankle and plantar flexion strength ratio at the last follow-up. The postoperative sports activity level and complications were also recorded. RESULTS: The mean operation duration and length of incision were 24.5 min and 2.0 cm. Whilst patient reported outcome questionnaires like AOFAS and ATRS showed good results, ROM of the ankle was quite low with only 16.5 degrees. Plantar flexion strength ratio was lower post surgery, as well. As for the postoperative sports activity level: 26/32 cases (81.3%) returned to former sports activity level; 4/32 cases (12.5%) showed a decline in sports activity level; 2/32 cases (6.2%) gave up on sports. The overall complication rate was 6.2%, one sural nerve damage and one fusiform thickening were found in the study. CONCLUSION: The percutaneous oval forceps suture-guiding method with anchor nails is a new considerable surgery method with adequate healing rates and an alternative to existing surgical procedures.

Chemical Interrogation of Nuclear Size Identifies Compounds with Cancer Cell Line-Specific Effects on Migration and Invasion.

Background: Lower survival rates for many cancer types correlate with changes in nuclear size/scaling in a tumor-type/tissue-specific manner. Hypothesizing that such changes might confer an advantage to tumor cells, we aimed at the identification of commercially available compounds to guide further mechanistic studies. We therefore screened for Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved compounds that reverse the direction of characteristic tumor nuclear size changes in PC3, HCT116, and H1299 cell lines reflecting, respectively, prostate adenocarcinoma, colonic adenocarcinoma, and small-cell squamous lung cancer. Results: We found distinct, largely nonoverlapping sets of compounds that rectify nuclear size changes for each tumor cell line. Several classes of compounds including, e.g., serotonin uptake inhibitors, cyclo-oxygenase inhibitors, ß-adrenergic receptor agonists, and Na+/K+ ATPase inhibitors, displayed coherent nuclear size phenotypes focused on a particular cell line or across cell lines and treatment conditions. Several compounds from classes far afield from current chemotherapy regimens were also identified. Seven nuclear size-rectifying compounds selected for further investigation all inhibited cell migration and/or invasion. Conclusions: Our study provides (a) proof of concept that nuclear size might be a valuable target to reduce cell migration/invasion in cancer treatment and (b) the most thorough collection of tool compounds to date reversing nuclear size changes specific to individual cancer-type cell lines. Although these compounds still need to be tested in primary cancer cells, the cell line-specific nuclear size and migration/invasion responses to particular drug classes suggest that cancer type-specific nuclear size rectifiers may help reduce metastatic spread.

Comparison of Open Reduction and Internal Fixation with Plate and Titanium Elastic Intramedullary Nail in Treating Pediatric Humeral Fracture.

OBJECTIVE: To investigate the therapeutic efficacy of titanium elastic intramedullary nail (TEN) and open reduction and internal fixation with plate (ORIF) in the treatment of humeral fracture in children. METHODS: A retrospective study was carried out in a total of 69 patients who were admitted to the hospital from January 2013 to December 2018. These patients, including 41 males and 28 females, were aged from 6 to 12 years old with a median of 8 years. These patients were diagnosed with humeral fracture and underwent the surgery of ORIF (n = 22) or TEN (n = 47). The intraoperative bleeding, operation time, length of stay (LOS), and fracture healing time were compared between the two groups. The therapeutic effect was assessed by the shoulder range of motion, the elbow range of motion, the UCLA shoulder function score, and the Mayo elbow performance score (MEPS) 6 months after the surgery. RESULTS: The intraoperative bleeding (97.20 ± 27.83 mL vs 185.60 ± 37.50 mL, P < 0.05), the operation time (53.70 ± 11.87 min vs 73.50 ± 13.33 min, P < 0.05), and the fracture healing time (9.30 ± 4.23 weeks vs 13.45 ± 3.67 weeks, P < 0.05) in the TEN group was significantly decreased than those in the ORIF group. There was no significant difference in the LOS between the two groups. The length of follow-up is 3 and 6 months. The shoulder range of motion (110.88° ± 15.82° vs 98.37° ± 16.22° at 3 months and 162.88° ± 17.29° vs 117.65° ± 19.38° at 6 months, both P < 0.05), the elbow range of motion (105.23° ± 2.81° vs 87.12° ± 4.73° at 3 months and 137.47° ± 4.82° vs 109.67° ± 5.83° at 6 months, both P < 0.05), and the UCLA shoulder function score (28.58 ± 4.74 vs 21.64 ± 7.23 at 3 months and 33.05 ± 3.27 vs 25.78 ± 3.87 at 6 months, both P < 0.05), and the MEPS (80.76 ± 3.53 vs 65.33 ± 9.43 at 3 months and 97.48 ± 1.23 vs 88.22 ± 3.65 at 6 months, both P < 0.05) in the TEN group were greater than those in the ORIF group. In the TEN group, complications occurred in three of 47 cases (6.38%), including one case (2.13%) of bone nonunion and two cases (4.25%) of irritation response around the nail. In the ORIF group, complications occurred in four of 22 cases (18.18%), including one case (4.55%) of delayed healing, one case (4.55%) of deep infection, and two cases (9.08%) of radial nerve injury. The complication rate was not significantly different between the two groups. CONCLUSION: TEN can be a good technique for the treatment of humeral fracture in children, with the advantages of less intraoperative bleeding, shorter operative time, quicker healing, and better recovery of shoulder range of motion and elbow range of motion.

Percutaneous reduction, cannulated screw fixation and calcium sulfate cement grafting assisted by 3D printing technology in the treatment of calcaneal fractures.

BACKGROUND: Percutaneous reduction, cannulated screw fixation and calcium sulfate cement grafting (PR + CSC) for treatment of displaced and intra-articular calcaneal fractures (DIACFs) is a difficult technique, because the minimally invasive treatment has limited exposure and cannot be used to reduce articular surface under direct vision. The goal of this study was to apply 3D printing technology to preoperative planning and surgery of DIACFs, and to evaluate its effectiveness, feasibility and safety in fracture repair. METHODS: We enrolled 81 patients with DIACFs in the study from August 2015 to August 2017. Patients with DIACFs in our hospital were randomly divided into the 3D printing group (40 cases) and the conventional group (41 cases). The operation duration, blood loss volume and the number of fluoroscopy were compared. Radiological results were evaluated using radiographs and functional results were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) score. The complications were also assessed. In addition, we made a questionnaire to verify the usefulness of the 3D printed model for both doctors and patients. RESULTS: The operation duration, blood loss volume and the number of fluoroscopy in 3D printing group were significantly less than that in the conventional group. Besides, 3D printing group achieved significantly better radiological results than conventional group both postoperatively and at the final follow-up except the calcaneal width at the final follow-up. The AOFAS score in the 3D printing group was significantly higher than that in the conventional group. In addition, the questionnaire from doctors and patients exhibited high scores of overall satisfaction of the 3D printed models. As for complications, there was no significant difference among the two groups. CONCLUSION: This study suggested the clinical feasibility of PR + CSC assisted by 3D printing technology in the treatment of DIACFs. LEVEL OF EVIDENCE: II.

[Endobutton and cortical screw fixation for the treatment of distal tibiofibular syndesmosis separated].

OBJECTIVE: To analyze the treatment effect of Endobutton plate cable system for the treatment of the distal tibiofibular syndesmosis injury. METHODS: Total 38 patients with tibiofibular syndesmosis separation treated by surgical operation from October 2011 to October 2013 were analyzed retrospectively. According to internal fixation, 38 cases were divided into two groups involving group A (cortical screw fixation) and group B (Endobutton plate cable system fixation). In group A, there were 26 patients including 16 males and 10 females with an average age of (37.90±4.67) years old ranging from 19 to 63 years old; 14 cases were on the left and 12 on the right;involving 8 cases of Weber-Denis type B, 18 cases of Weber-Denis type C; according to Lauge-Hanson typing, 9 cases of supination external rotation (SER), 10 cases of pronation abduction (PAB), 7 cases of pronation external rotation (PER). In group B, there were 12 cases including 7 males and 5 females, with an average age of (38.70±6.03) years old ranging from 20 to 55 years old;6 cases were on the left and 6 cases on the right;involving 4 cases of Weber-Denis type B and 8 cases of Weber-Denis; involving 7 cases of PER, 3 cases of SER, 2 cases of PAB. The operative time, intraoperative blood loss, surgery cost, hospital stay time, the wound healing, pain score at 1 month after operation, and the load time were recorded and evaluated. According to reviewing of X rays regulary, the healing of fracture were assessed, the function outcomes of ankle was evaluated according to the Ankle Hind Foot Scale of American Orthopaedic Foot and Ankle Society. RESULTS: All patients were followed up for 8 to 18 months with an average of 13.5 months. There were no statistical significance in intraoperative blood loss, hospital stay time, average load time and postoperative pain score at 1 month after operation between two groups (P>0.05). Duration of operation, the operative time were significantly shorter in cortical screw group;however, the average cost of hospitalization was significantly higher in Endobutton group. No significant differences were found between two groups in outcome of radiographic measurement. The X rays of 36 patients showed well healing of fracture, normal mortise and no distal tibiofibular syndesmosis separation. AOFAS score at the final follow up in group A was (87.50±8.67) scores, 18 cases got excellent result, 4 cases were good, and 4 cases were fair. AOFAS score at the final follow up in group B was (86.23±7.42) scores, 7 cases obtained excellent result, 4 cases were good and 1 case was fair; AOFAS score between two groups were no significant difference (P>0.05). CONCLUSIONS: Endobutton plate cable system is a dynamic capital equipment in treating the tibiofibular syndesmosis separation, it has a similar outcome compared with the screw, but without screw fractured and do not regular remove after operation. The patients could take the functional exercises earlier.

Differentiation of menstrual blood-derived stem cells toward nucleus pulposus-like cells in a coculture system with nucleus pulposus cells.

STUDY DESIGN: Human stromal stem cells derived from menstrual blood (MenSCs) and nucleus pulposus (NP) cells were cocultured under normal or low oxygen (O2) condition. OBJECTIVE: To assess the differentiation capability of MenSCs toward nucleus pulposus cells under normal or low oxygen condition. SUMMARY OF BACKGROUND DATA: Given the proliferative capacity and pluripotentiality of mesenchymal stem cells, mesenchymal stem cells transplantation is thought to be a promising approach to managing intervertebral disc degeneration. METHODS: Using coculture plates with 0.4-µm pore size polyethylene terephthalate track-etched inserts, MenSCs and NP cells (1:1 ratio) were cocultured with cell-to-cell contact for 2 weeks in normal (20% O2) or low oxygen tension (2% O2), respectively. Extracellular matrix accumulation was quantified by dimethylmethylene blue assay, histological staining, and quantitative reverse-transcription polymerase chain reaction. Novel characteristic human NP markers cytokeratin-19 (KRT19), carbonic anhydrase XII (CA12), and forkhead box F1 (FoxF1) were also detected by quantitative reverse-transcription polymerase chain reaction. RESULTS: The result of quantitative reverse-transcription polymerase chain reaction showed that aggrecan and COL2A1 genes expression was significantly increased in differentiated MenSCs (P < 0.05). There was significantly more COL2A1 gene expression in normoxic group than that in low O2 group (P < 0.05). But no significant difference was observed in aggrecan gene expression between normoxic group and low O2 group. These aforementioned results were also confirmed by histological analysis. We also found that the characteristic NP markers (KRT19, CA12, FoxF1) were significantly upregulated in differentiated MenSCs. Moreover, low O2 tension (2%) further enhanced these genes expression (P < 0.05). CONCLUSION: In our study, MenSCs were successfully differentiated into NP-like cells and may become a new source of seed cells for the treatment of intervertebral disc degeneration in the future. LEVEL OF EVIDENCE: N/A.