Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

ObjectiveTo investigate the infection and genotypes of Wolbachia in Aedes albopictus. MethodsAdult and larval samples of Aedes albopictus were collected from different residential and wild areas from 2020 to 2021， Wolbachia surface protein （wsp） gene was amplified and genotyped for wAlbA and wAlbB by PCR， and sequenced for phylogenetic analysis. The difference of detection rate among different habitats， male and female adult mosquitoes， adult and larvae was compared by χ² analysis. ResultsThe detection rate of Wolbachia in adult and larvae of Aedes albopictus were 43.5% （77/177） and 70.4% （190/270）， respectively， with a statistically significant difference （χ²=32.086，P<0.001）， and wAlbA and wAlbB were mainly detected together. The detection rate of Wolbachia in female and male Aedes albopictus were 50.7% （76/150） and 3.7% （1/27）， respectively， with a statistically significant difference（χ²=20.533，P<0.001）. The detection rate of adult Aedes albopictus in Songjiang wild area， residential area and Hongkou residential area were 91.7% （55/60）， 18.8% （22/117） and 41.7% （30/72）， respectively， with a statistically significant difference （χ²=54.322，P<0.001）. Genotyping and phylogenetic analysis showed that adult and larvae of Aedes albopictus infected with Wolbachia were mainly wAlb A and wAlb B. In addition， some sequences formed clades independently， and the genetic distance from other sequences was relatively large. ConclusionInfection of Wolbachia in Aedes albopictus is relatively common in Songjiang District. The main genotypes are wAlb A and wAlb B and there may be other subtypes， which are worthy of further exploration and research.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective:To analyze and summarize the key points of design and implementation of new drug clinical trials for ankylosing spondylitis.Methods:The platform for drug clinical trial registration and information published on the official website of center for drug review and evaluation of national medical products administration (CDE) was searched to obtain data and classified statistics was conducted then. The Mean±SD and M ( Q1, Q3) were used for quantitative data for statistical description, and the rate, composition or relative ratio of qualitative data were used for statistical description. Results:A total of 23 clinical trials meeting the requirements were screened, among which 19 were biological products included in nine phase Ⅲ clinical trials. Among the four chemical drugs, two were phase Ⅱ clinical trials. One of the clinical trials on AS adopted the 1966 New York classification criteria, accounting for 4%. Nineteen of the trials adopted the1984 New York classification criteria, accounting for 83%. Three other trials adopted unspecified classification criteria, accounting for 13%. In one of these clinical trials, the age of patients included was older than 16 years old, 9 trials were 18 to 65 years old, 6 were 18 years old but without upper limit. In the definition of active AS, 19 trials took BASDAI≥4 as the cut-off value for active disease, and BASDAI, total back pain, spinal pain and morning stiffness were regarded as active disease in 4.Conclusion:The number of dosestic AS clinical trial projects continnes to rise. The 1984 classification criteria is adopted as the classification criteria in clinical trials. The minimum age in the inclusion criteria is 18 years old, there is no upper limit in age for inclusion. Disease activity can be evaluated by BASDAI score, combined with comprehensive indicators such as night-time back pain, global spinal pain and morning stiffness.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

This study analyzed the inhibitory effects of BCX4430 on rabies virus with different virulence(CVS-11 and SC16)in vitro.Direct immunofluorescence(DFA),quantitative real-time PCR and half tissue culture infective dose(TCID50)assays were used.BCX4430(250 pmol/L),compared with T-705,significantly decreased the viral titer and the relative expres-sion level of viral mRNA,similarly to the inhibitory effects of ribavirin.Thus,our study demonstrated that BCX4430 signifi-cantly inhibits the replication of rabies virus in vitro.

Objective:To investigate the clinical characters and prognostic value of PSA flare and bone flare in metastatic castration resistant prostate cancer(mCRPC) patients received Abiterone acetate(AA) therapy.Methods:A retrospective study was conducted for 93 mCRPC patients treated with AA from Jul.2016 to Dec.2020. Mean age was (75.4±8.9)years, median PSA was 58.2 (16.4, 148.6)ng/ml. Patients received at least 6 months of AA treatment. PSA flare was defined as an increase of PSA after AA therapy followed by a decrease. Bone flare was defined as disease progression after 3 months of therapy, typically based on increased lesion intensity or number, and reevaluation 6-9 months later showed improvement in the scan. The clinical characters and prognostic value of the flare phenomenon was evaluated and analyzed respectively.Results:The median follow up time was 16 months(6, 54 months), fourteen patients showed PSA flare at first month after AA treatment, and median time of duration was 2 months(1, 7 months). The serum alkaline phosphatase (ALP) had a similar rising trend along with PSA flare[115.5(98.0, 198.5)U/L vs. 119.0(97.0, 288.8)U/L, P=0.016]. Seven patients showed bone flare and 3 cases co-existed with PSA flare. Multivariate Cox regression analysis indicated bone flare was an independent protective factor for progression free survival(PFS)( HR=0.117, 95% CI 0.015-0.895, P=0.039), PSA flare had no significant influence on PFS ( HR=1.314, 95% CI 0.554-3.121, P=0.536)and overall survival(OS)( HR=1.348, 95% CI 0.393-4.263, P=0.635). Log-rank test showed patients with bone flare had a longer PFS( P=0.016) and OS( P=0.047) compared with patients without bone flare. Conclusions:PSA flare always faded away after 2 months AA therapy and had no influence on PFS and OS. Bone flare maybe an indication for better prognosis.

OBJECTIVE: To explore the effectiveness of hairpin shaped incision combined with cover-lifting flap in plastic surgery of huge fat pad on nape and back. METHODS: Between March 2019 and March 2023, 10 patients with huge fat pad on the nape and back were treated. There was 1 male and 9 females with an average age of 52 years (range, 39-57 years). All patients had soft tissue bulge on the nape and back. Preoperative MRI showed the subcutaneous fat thickening. The length of the longitudinal axis of the fat pad ranged from 10.0 to 25.0 cm (mean, 14.1 cm), the length of the transverse axis ranged from 6.0 to 15.0 cm (mean, 10.8 cm); the thickness of the fat pad ranged from 2.5 to 5.1 cm (mean, 3.9 cm). Under general anesthesia, the patient was placed in a prone position and a hairpin shaped incision was made. The flap was lifted to remove the fat pad according to the marked area. The dressing was changed every 2 days after operation. RESULTS: The operation time was 35-110 minutes (mean, 72 minutes). The intraoperative blood loss was 35-80 mL (mean, 49.5 mL). The drainage tube was removed at 2-5 days after operation (mean, 3.4 days). All incisions healed by first intention without incision dehiscence, infection, subcutaneous bruising, hematoma, or other related complications. All patients were followed up 2-24 months (mean, 12 months). All patients had a good shape of the nape and back and no noticeable scar on the incision. According to the Vancouver Scar Scale evaluation criteria, the incision scar score was 3-5 (mean, 3.7) at 2 months after operation. Patients had good neck movement with no recurrence. CONCLUSION For the huge fat pad on the nape and back, the plastic surgery using hairpin shaped incision and cover-lifting flap has the advantages of fully exposing the fat pad, concealed incision, simple operation, and natural shape of the nape and back after operation.
Female ; Humans ; Male ; Middle Aged ; Surgery, Plastic ; Cicatrix ; Lifting ; Plastic Surgery Procedures ; Surgical Wound ; Adipose Tissue