Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

Neurological impairment in the form of stroke,cognitive dysfunction and delirium is a common complication after cardiac surgery and a major cause of postoperative death and long-term disability in patients undergoing cardiac surgery.There have been many studies attempting to identify intervention and treatment strategies,but no standardized protocols for neurological protection have been developed.The purpose of this article is to discuss the risk factors,mechanisms and neuroprotective measures to improve patient prognosis of neurological injury after cardiac surgery,and to review the recent research progress from three aspects:preoperative assessment and intervention,intraoperative management and monitoring,and postoperative diagnosis and treatment,emphasizing that the focus of perioperative prevention and treatment should be on the prevention of ischemic-hypoxic injury.Future research directions should focus on translational research of preclinical experiments and the development of novel imaging techniques to reduce the incidence of neurological complications and improve clinical outcome.

Objective: To understand the infection status and epidemiological characteristics of hepatitis C in people aged 1-69 years in Henan Province in 2020. Methods: The estimated sample size was 5 827. From August to December 2020, multistage sampling was used to select 8 counties (districts) in Henan, and two survey sites were selected in each county (district), and a questionnaire survey was conducted in local people aged 1-69 years, blood samples were collected from them for anti-HCV, HCV RNA and genotype detections. Results: A total of 5 165 people aged 1-69 years completed the questionnaire survey. Men accounted for 44.76% (2 312/5 165), women accounted for 55.24% (2 853/5 165). In the people aged 1-69 years, the overall prevalence rates of anti-HCV and HCV RNA were 0.69% (95%CI: 0.68%-0.70%) and 0.20% (95%CI: 0.19%-0.21%) respectively. The prevalence rates of anti-HCV and HCV RNA were 0.48% (95%CI: 0.46%-0.50%), 0.09% (95%CI: 0.08%-0.10%) in men and 0.86% (95%CI: 0.85%-0.87%), 0.30% (95%CI: 0.28%-0.32%) in women. The prevalence rates of anti-HCV and HCV RNA increased with age. The prevalence rates of anti-HCV and HCV RNA were 0.87% (95%CI: 0.86%-0.88%), 0.28% (95%CI: 0.26%-0.30%) in urban residents and 0.53% (95%CI: 0.51%-0.55%), 0.14% (95%CI: 0.13%-0.15%) in rural residents. The genotyping results of 10 HCV RNA positive samples ware genotype 1b (4/10), genotype 2 (3/10), genotype 1b/3 (1/10), genotype 1b/3/6 (1/10) and genotype 2/6 (1/10). Conclusions: The prevalence of hepatitis C was low in Henan in 2020. It is necessary to strengthen hepatitis C surveillance in people aged 40 years and above. The major HCV genotypes were 1b and 2, and mixed genotype infection existed.
Female ; Humans ; Male ; Coinfection ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/epidemiology* ; Hepatitis C Antibodies/genetics* ; Prevalence ; RNA, Viral/genetics* ; Surveys and Questionnaires ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

China ; Cognition ; Digestive System Surgical Procedures ; Enhanced Recovery After Surgery ; Humans ; Length of Stay

OBJECTIVE: This study evaluated the effect of maximal oxygen pulse (O ₂P _max) on patients with chronic obstructive pulmonary disease (COPD) and confirmed the predictive effect on acute exacerbations of COPD (AECOPD). METHODS: This retrospective study included 91 participants who underwent cardiopulmonary exercise testing (CPET), lung function testing, a dyspnea scale assessment, and a 3-year follow-up. The participants were divided into two groups according to the O ₂P _max value. Exercise capacity, ventilatory conditions, gas exchange efficiency, and dyspnea symptoms were compared, and the correlations between O ₂P _max and these indices were evaluated. The ability of O ₂P _max to predict AECOPD was examined. RESULTS: Exercise capacity, ventilatory conditions, and gas exchange efficiency were lower, and dyspnea symptom scores were higher in the impaired O ₂P _max group ( P < 0.05). O ₂P _max was positively correlated with forced vital capacity (FVC)%, forced expiratory volume in 1 sec (FEV ₁)%, FEV ₁/FVC%, anaerobic threshold (AT), work rate (WR)%, aximal oxygen uptake (V̇O _2max)%, V̇O ₂/kg _max, V̇O ₂/kg _max%, WR _AT, WR _max, V̇O _2AT, V̇O _2max, and V̇ _Emax, and was negatively correlated with EqCO _2AT, and EqCO _2max ( P < 0.05). Most importantly, O ₂P _max could be used to predict AECOPD, and the best cut-off value was 89.5% (area under the curve, 0.739; 95% CI, 0.609-0.869). CONCLUSION O ₂P _max reflected exercise capacity, ventilation capacity, gas exchange capacity, and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.
Dyspnea/etiology* ; Exercise Tolerance ; Humans ; Oxygen ; Oxygen Consumption ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies

Objective To summarize the clinical characteristics of recipients of renal transplantation who used tacrolimus extended-release capsules,to optimize the postoperative immunosuppressive regimen,and provide reference for the therapeutic administration of imnmunosuppressive agents after renal transplantation.Methods 156 patients who had renal transplant in our center were divided into three groups according to the time of the change of the extended-release tacrolimus capsules,and the blood glucose and blood lipids of each group were analyzed.Results The longer the postoperative duration was,the higher proportion of new-onset diabetes cases (P =0.025).There was no significant difference among the three groups of immune induction regimens.The immnunosuppressive regimen was changed from MMF (68.8％ in G3 group) to MPA (72％ in G1 group).With the prolongation of postoperative time,the dosage of tacrolimus decreased gradually.The mean tacrolimus concentration in the 3 groups was significantly different (P＜0.001) as time went by.There was no significant change in the average daily dosage before and after the change.The trough value before and after the change in the first two groups was significantly different (P＜0.001).Conclusion The extended-release tacrolimus capsules could be used in different stages after renal transplantation.After the conversion of the extended-release tacrolimus capsules,the dosage of adjuvant is reduced,and blood concentration and creatinine level are more stablem which is a more optimized immunosuppressive regimen.

BACKGROUNDThe properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA.

METHODSA medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.

RESULTSCartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks.

CONCLUSIONThe microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.

Animals ; Collagen ; metabolism ; Male ; Osteoarthritis ; diagnostic imaging ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; X-Ray Microtomography

Objective To investigate the pharmacokineics and bioavai-lability of recombinant fully human anti -tumor necrosis factor -α( TNF-α) amonoclonal monoclonal antibody. Method Twenty machins were subcutaneous or intravenous given fully human anti -TNF-αamonoclonal monoclonal antibody (1, 3 or 10 mg· kg -1 ).By using the validated enzyme -linked immuno sorbent assay ( ELISA ) kits for the determination of content of fully human anti -TNF-αamono-clonal monoclonal antibody in the plasma of machines , in order to study the pharmacokineics within 168 h and bioavailability.Result After the subcutaneous administration of 1, 3 and 10 mg· kg -1 of fully human anti-TNF-αamonoclonal monoclonal antibody injection , the AUC0-168 in-creased ( P<0.05 ) , but not the t1/2 , Vz/F, CL/F increased with the dose.The bioavailability of fully human anti -TNF -αamonoclonal monoclonal antibody after subcutaneous administration was 77.5%.Con-clusion In the range of administration concentration of this study , the plasma exposure of fully human anti -TNF-αamonoclonal monoclonal antibody had a linear pharmacokinetic profile in machin within 168 h after administration.Fully human anti -TNF -αamonoclonal mono-clonal antibody was well absorbed with a high bioavability.

OBJECTIVETo explore the effects of different doses of P-8 in increasing the Hypoxia tolerance of mice and the mechanisms involved.

METHODSThe health mice were placed into the oxygen deficit bottles and measured the survival time in the condition of hypoxia. The male mice were put into the ladder cage, then placed them into the hypobaric champer to determine the survival time of mice with decompression hypoxia (min). We observed the activity changes of the mice's organization carbonic anhydrase II (CAII). By using the drug in prophylaxis, we investigated the effects of carbonic anhydrase target-based inhibitors P-8 for improving the hypoxia tolerance.

RESULTS(1) In improving the endurance of mice in the condition of hypoxia, the survival time of 6.25 mg/(kg x d) and more doses of P-8 groups were (27.38 +/- 4.63, 29.53 +/- 4.43, 29.67 +/- 7.28, 31.55 +/- 6.34, 32.45 +/- 6.65, 36.81 +/- 7.24 and 35.41 +/- 4.20) min, compared with the control group (22.90 +/- 3.19) min , the survival time significantly prolonged (P < 0.05, P < 0.01); compared to the same dose of acetazolamide groups (24.54 +/- 3.17, 22.70 +/- 3.04, 22.67 +/- 2.99, 23.93 +/- 0.96, 27.87 +/- 5.06, 30.79 +/- 5.12 and 35.14 +/- 6.46) min, the survival time significantly prolonged; P-8 groups and Acetazolamide's minimum effective dose were 6.25 and 100 mg/(kg x d), the potency of P-8 is 16 times Acetazolamide. (2) In improving the endurance of mice in the condition of hypoxia, the survival time of middle and high doses of P-8 groups [(24.82 +/- -3.92, 28.27 +/- 5.89) min] were significantly longer than those in control group [(21.96 2.51) min, P < 0.05]; compared with the acetazolamide (23.11 +/- 3.71) min, the survival time of high dose of P-8 group was significantly prolonged. (3) Compared with the normal control group, P-8 [(25 mg/(kg x d), 50 mg/(kg x d), 100 mg/(kg x d), 200 mg/(kg x d)] dose groups inhibited the activity of carbonic anhydrase II (CAII) in the renal (P < 0.05, P < 0.01); P-8 [100 mg/(kg x d) and 200 mg/(kg x d)] dose group significantly inhibited the activity of carbonic anhydrase II (CA II) in the brain (P < 0.05).

CONCLUSIONP-8 treatment improved the endurance of mice in the condition of hypoxia and worked better than Acetazolamide. The mechanism may be related to the inhibition of carbonic anhydrase organization.

Adaptation, Physiological ; physiology ; Altitude Sickness ; prevention & control ; Animals ; Carbonic Anhydrase Inhibitors ; pharmacology ; therapeutic use ; Hypoxia ; physiopathology ; Male ; Mice