ObjectiveTo analyze the long-term trend of incidence and mortality of type 2 diabetic kidney disease （DKD） in China from 1990 to 2021. MethodsThe Joinpoint regression model was used to analyze the average annual percentage change （AAPC） of standardized incidence rate and standardized mortality rate， and the age-period-cohort （APC） model was constructed to analyze the longitudinal age change， period and cohort effect risk ratio （RR）. ResultsFrom 1990 to 2021， the standardized incidence rate of type 2 DKD in males and females showed an overall upward trend， with AAPC of 0.08% and 0.36%， respectively. The age-standardized mortality rate of the total population and female showed a downward trend， with AAPC of -0.61% and -1.03%， respectively. However， there was no significant difference in males. APC model showed that the age effect existed： the peak age was 75-79 years old， the mortality rate of females increased， and the mortality rate of males decreased after 80-84 years old. For the effect of time period， the risk of type 2 DKD incidence in females in 2017—2021 was 1.05 times that in 2002—2006， and the risk of death in males and females in 2017—2021 was 0.84 and 0.71 times that in 2002—2006， respectively. For cohort effects， the highest risk of disease was seen in men and women born in 1967—1971， and the highest risk of death was seen in men born in 1952—1956 and women born in 1912—1916. ConclusionFrom 1990 to 2021， the standardized incidence rate of type 2 DKD in China shows an upward trend， and the standardized mortality rate shows a downward trend. It is necessary to strengthen the health behavior publicity and education of type 2 DKD， and actively carry out early screening to reduce the disease burden.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.

OBJECTIVE To explore the effect of tracking methodology on investigation of contamination incidents of bronchoalveolar lavage fluid(BALF)specimens from the children.METHODS The onsite tracking was carried out for the contamination incidents of BALF specimens of the children through the tracking methodology,the quality control processes of cleaning and disinfection of bronchofiberscopes and the tracking routes were determined.The quality control process of cleaning and disinfection of bronchofiberscopes were evaluated,the existing risks were found out,and the specific improvement measures were formulated.RESULTS The onsite tracking was carried out for the incident of carbapenem-resistant Klebsiella pneumoniae(CRKP)that was caused by the contamination of 12 BALF specimens from pediatrics department wards before and after Nov.1,2021.No.2180014C bronchofiber-scope without biological surveillance was determined as the high-risk point of contamination of BALF specimens,the monitoring procedure of cleaning and disinfection of the bronchofiberscopes was revised.The BALF specimens that were submitted from Dec.1,2021 to Dec.31,2021 were tracked,and no CRKP was detected among the 23 submitted specimens.Totally 12 bronchofiberscope specimens were collected for biological surveillance,and the qualified rate was 100.00％.The treatment rooms of pediatrics department,hand disinfection effect of health care workers of cleaning and disinfection rooms and disinfection effect of object surfaces were monitored,and the quali-fied rate was increased from 98.39％to 100.00％.CONCLUSIONS The tracking methodology is an effective tool for quality management and can be used for evaluation of quality process of cleaning and disinfection of bronchofi-berscopes,which may find out the causes for adverse events in a timely manner and raise the medical safety.

Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.

The amino-terminal pro-C-type natriuretic peptide(NT-proCNP)is a diagnostic inflam-matory marker clinically used for diagnosing bacterial infections.This study aims to establish a phage display library of single-chain variable fragment(scFv)antibodies against canine NT-proC-NP and to screen for scFvs with high binding affinity to NT-proCNP.Initially,NT-proCNP was prepared using prokaryotic expression system and was used to immunize New Zealand White rab-bits.Upon achieving the desired serum titer,total RNA was extracted from the splenocytes of rab-bits and reverse transcribed into cDNA.Using this cDNA as a template,degenerate primers were employed to amplify the genes of the rabbit antibody light chain variable region(VL)and heavy chain variable region(VH).The VL and VH regions were spliced together to form a complete scFv fragment via overlap extension PCR.The scFv was then ligated into the phagemid pComb3XSS and electroporated into competent E.coli TG1 cells to construct a rabbit-derived anti-NT-proCNP scFv immunological library.This library underwent four rounds of enrichment and screening to isolate specific single-chain antibodies.The selected antibody was subsequently ex-pressed in a soluble form within a prokaryotic system,and its immunological activity was evalua-ted.Using phage display technology,this study successfully identified a single-chain antibody scFv-1-CNP with strong antigen-binding activity and genetic sequence characteristics of scFvs,providing a research direction for further exploration of scFv applications in the detection of NT-proCNP.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.