Objective: To discuss the epidemiological characteristics of hand foot mouth disease (HFMD) among children in Jiujiang City, and its correlation with meteorological factors, so as to provide scientific evidence for developing targeted HFMD prevention and control measures. Methods: HFMD incidence data among children and meteorological factor records from Jiujiang City during 2019-2023 were collected. Pearson correlation analysis and Quasi-Poisson regression analysis of generalized additive model were used to analyze the relationship between the number of cases and meteorological factors, calculating correlation coefficients (r) and excess risk (ER). Results: The annual reported children HFMD cases in Jiujiang City during 2019-2023 were 4 299, 4 671, 2 560, 3 230, and 3 584, respectively. Except for a peak in autumn-winter in 2020, outbreaks occurred mainly in spring and summer in other years. The majority of cases involved scattered children (71.11%) and children in daycare centers (26.64%). Pearson correlation analysis showed that total case counts, cases among scattered children, and cases among children in daycare centers were positively correlated with average temperature ( r =0.36, 0.39, 0.23), maximum temperature ( r =0.32, 0.36, 0.20), minimum temperature ( r =0.37, 0.41, 0.24), and average relative humidity ( r =0.19, 0.20, 0.15) (all P <0.05). Quasi-Poisson regression analysis of generalized additive model revealed that total cases, cases among scattered children, and cases among daycare children were positively associated with average temperature ( r =0.05, 0.06, 0.03) and average relative humidity ( r =0.03, 0.02, 0.02) (all P <0.01). Excess incidence risk analysis indicated that for every 10 ℃ increase in average temperature, the ER (95% CI ) values were 72.16 (45.91-103.14), 79.76 (52.99- 111.23 ) and 39.30 (14.45-69.54) among total children, scattered children and daycare children, respectively; for every 10% increase in average relative humidity, the ER (95% CI ) values were 28.69 (12.22-47.56), 27.81 (12.01-45.84) and 24.42 (5.56-46.65), respectively. Conclusions The incidence level of HFMD among children in Jiujiang City is positively correlated with the average temperature and average relative humidity. Higher temperature and humidity are associated with an increased risk of excess HFMD incidence in scattered children compared to children in daycare centers.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

OBJECTIVE To investigate the improvement effect and mechanism of processed Oxytropis falcata on renal fibrosis （RF） in rats. METHODS RF model was induced by adenine. After modeling， the rats were divided into the model group， positive control group （colchicine， 0.45 mg/kg）， and processed O. falcata low-， medium- and high-dose groups （0.5， 1， 2 g/kg）， respectively. Additionally， a blank group without modeling was set up， with 8 rats in each group. The positive control group and the various dosage groups of processed O. falcata were given the corresponding medicinal solutions intragastrically， while the blank group and model group were given equal volume of normal saline intragastrically， once daily for 28 consecutive days. The appearance and histopathological morphology of the rats’ kidneys were observed. Serum levels of renal function indexes [bl ood urea nitrogen （BUN）， creatinine （Cr） ] and inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） ] in rats were detected. Protein expressions of fibronectin （FN）， α -smooth muscle actin （ α -SMA） and collagen type Ⅰ （Col-Ⅰ） in renal tissue of rats were determined. mRNA expressions of transforming growth factor-β 1 （TGF-β 1 ）， Smad3 and extracellular signal-regulated kinase 1/2 （ERK1/2） in renal tissues were measured. Protein expression of TGF-β 1 and phosphorylation levels of Smad3 and ERK1/2 in renal tissues were detected. RESULTS Compared with the blank group， the rats in the model group exhibited enlarged kidneys with pale color， rough and uneven surface. There was a significant infiltration of inflammatory cells and vacuolated cells in the renal tubules， along with marked proliferation of collagen fibers. Serum levels of BUN， Cr， IL-6 and TNF-α， protein expressions of α -SMA， Col-Ⅰ and FN in renal tissues， mRNA expressions of TGF-β 1 ， Smad3， ERK1 and ERK2 and protein expression of TGF-β 1 as well as phosphorylation levels of Smad3 and ERK1/2 in renal tissues were increased significantly （ P ＜0.05）. Compared with the model group， renal pathological changes of rats were alleviated in processed O. falcata groups， with reduced infiltration of inflammatory cells and proliferation of collagen fibers. The levels of the aforementioned quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Processed O. falcata can improve renal function in RF rats， alleviate inflammatory responses， and reduce abnormal collagen fiber deposition. Its mechanism of action may be related to the inhibition of the activity of the TGF-β 1 /Smad signaling pathway.

OBJECTIVE: To develop and compare risk prediction models for in-hospital post-cardiac arrest brain injury (PCABI) in critically ill patients using nomograms and random forest algorithms, aiming to identify the optimal model for early identification of high-risk PCABI patients and providing evidence for precise treatment. METHODS: A retrospective cohort study was used to collect the first-time in-hospital cardiac arrest (IHCA) patients admitted to the intensive care unit (ICU) from 2008 to 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) as the study population, and the patients' age, gender, body mass, health insurance utilization, first vital signs and laboratory tests within 24 hours of ICU admission, mechanical ventilation, and critical care scores were extracted. Independent influencing factors of PCABI were identified through univariate and multivariate Logistic regression analyses. The included patients were randomly divided into a training cohort and an internal validation cohort in a 7:3 ratio, and the PCABI risk prediction model was constructed by the nomogram and random forest algorithm, respectively, and the model was evaluated by receiver operator characteristic curve (ROC curve), the calibration curve, and the decision curve analysis (DCA), and after the better model was selected, 179 patients admitted to Tianjin Medical University General Hospital as the external validation cohort for external evaluation were collected by using the same inclusion and exclusion criteria. RESULTS: A total of 1 419 patients with without traumatic brain injury who had their first-time IHCA were enrolled, including 995 in the training cohort (including 176 PCABI and 819 non-PCABI) and 424 in the internal validation cohort (including 74 PCABI and 350 non-PCABI). Univariate and multivariate analysis showed that age, potassium, urea nitrogen, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation III (APACHE III), and mechanical ventilation were independent influences on the occurrence of PCABI in patients with IHCA (all P < 0.05). Combining the above variables, we constructed a nomogram model and a random forest model for comparison, and the results show that the nomogram model has better predictive efficacy than the random forest model [nomogram model: area under the ROC curve (AUC) of the training cohort = 0.776, with a 95% credible interval (95%CI) of 0.741-0.811; internal validation cohort AUC = 0.776, with a 95%CI of 0.718-0.833; random forest model: AUC = 0.720, with a 95%CI of 0.653-0.787], and they performed similarly in terms of calibration curves, but the nomogram performed better in terms of decision curve analysis (DCA); at the same time, the nomogram model was robust in terms of external validation cohort (external validation cohort AUC = 0.784, 95%CI was 0.692-0.876). CONCLUSIONS A nomogram risk prediction model for the occurrence of PCABI in critically ill patients was successfully constructed, which performs better than the random forest model, helps clinicians to identify the risk of PCABI in critically ill patients at an early stage and provides a theoretical basis for early intervention.
Humans ; Critical Illness ; Retrospective Studies ; Heart Arrest/complications* ; Nomograms ; Brain Injuries/etiology* ; Intensive Care Units ; Algorithms ; Male ; Female ; Middle Aged ; ROC Curve ; Risk Factors ; Risk Assessment ; Logistic Models ; Aged

Objective:The aim of this study was to present an institution's experience with cochlear reimplantation（CRI）, to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. Methods:We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features include caused of CRI, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance （CAP） and Speech Intelligibility Rating （SIR） scores were used to evaluate pre-and post-CRI outcomes. Our center's consecutive cohort of 1 126 patients had seven patients, while 69 patients were from other cochlear implant centers. Device failure was the most common cause of CRI（68/76）, with the remaining cases including flap complications（3/76）, magnet displacement（3/76）, secondary meningitis（1/76）, and foreign bodies around the implant（1/76）. Postoperative auditory and speech outcome improved in 31.6%（24/76） of patients, remained unchanged in 63.2%（48/76）, and decreased in CAP and SIR scores in 5.2%（4/76） of patients. Postoperatively, the seven patients with cochlear ossification and fibrosis scored lower on the overall CAP and SIR scale than non-ossification individuals, which is a significant factor in surgical success rates and auditory-speech outcomes. Conclusion:CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, minimally invasive CI has a positive significance for reducing the difficulty of CRI surgery and improving the CI performance.
Humans ; Cochlear Implantation/methods* ; Retrospective Studies ; Cochlear Implants ; Male ; Female ; Postoperative Period ; Treatment Outcome ; Adult ; Speech ; Middle Aged ; Postoperative Complications ; Replantation ; Cochlea/surgery*

Objective:To introduce a new design of super-micro flap for endoscopic ear surgery, and to evaluate the application effect of super-micro flap in endoscopic tympanoplasty. Methods:Between January, 2023 and March, 2024, 58 patients（64 ears） with tympanosclerosis underwent tympanoplasty with super-micro flap. Continuous irrigating mode endoscopic ear surgery（CIM-EES） was used to complete type Ⅱ or Ⅲ tympanoplasty with the tragus cartilage with followed up for 12 to 24 months. The operation time, postoperative efficacy and complications were statistically analyzed. Results:Of the 64 ears, 63 ears had primary healing of the tympanic membrane, and 1 ear had cartilage necrosis due to multi-drug resistant bacteria infection. The second operation was performed one year later, and the success rate of operation was 98.40%. The average operation time was （48.40±8.86） minutes. The average hearing threshold of 0.5 kHz to 4.0 kHz before operation was （59.63±10.62） dB HL, and the average air conduction threshold of 0.5 kHz to 4.0 kHz one year after operation was（38.79±10.91） dB HL, which was significantly improved compared with that before operation（P<0.01）. Bone conduction threshold also improved significantly （24.49±8.55） dB HL vs（21.88±7.58） dB HL（P<0.01）. No outer tympanic membrane healing and ear canal scar stenosis occurred. Conclusion:The design of super-micro flap can effectively solve the interference of flap floating during continuous irrigating mode in endoscopic ear surgery, relieve the difficulty of flap reposition, simplify the operation process, help to shorten the operation time, and reduce the possibility of circular scar stenosis of conventional free flap, which provides a new flap design option for endoscopic ear surgery.
Humans ; Tympanoplasty/methods* ; Endoscopy/methods* ; Surgical Flaps ; Male ; Female ; Adult ; Myringosclerosis/surgery* ; Middle Aged ; Treatment Outcome ; Tympanic Membrane/surgery* ; Adolescent ; Young Adult

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease （NAFLD）， especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years， analyzes the latest research advances in the epigenetics of NAFLD in this population， and briefly describes the basic concepts of epigenetics， including DNA methylation， histone modifications， and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis， disease progression， and treatment strategies of NAFLD in lean individuals.