Objective This paper focuses on the manufacturing technique of bubble microneedles and temperature-sensitive materials in order to design and prepare a temperature-sensitive reservoir microneedle.The objective is to evaluate the feasibility of addressing the issue of low drug load in traditional Chinese medicine(TCM)external preparations using microneedles.Methods The study involved the utilization of sinomenine hydrochloride as the model drug.The drug,along with the temperature-sensitive material N-isopropylacrylamide,was filled into the cavity of the bubble microneedle made from chitosan.Through positioning and curing processes,a temperature-sensitive sinomenine hydrochloride reservoir microneedle was prepared.The microneedle consisted of a needle body,a positioning layer,a basal layer,and a drug reservoir.The drug load,size,length,mechanical properties,and puncture ability of the prepared reservoir microneedle were measured to characterize and evaluate its drug load and mechanical properties.In addition,the in vitro release characteristics of the microneedles were determined using Franz diffusion cells,while the in vivo release characteristics were evaluated using the percutaneous microdialysis technique.Results The research result demonstrated that the prepared temperature-sensitive reservoir microneedle had a drug load of approximately 5.76 mg/cm2.The exposed needle tip had a conical shape with a height of around 650 μm,exhibiting good mechanical strength and skin puncture ability.The in vitro release tests showed that the microneedle could simulate the temperature of the skin and release the drug in a controlled and gradual manner,displaying characteristics of diffusion and dissolution of the skeleton.Furthermore,compared to conventional external preparations,the reservoir microneedles significantly enhanced transdermal permeation of the drug in the in vivo percutaneous studies.Conclusion The study demonstrated that reservoir-type microneedles prepared using temperature-sensitive materials and bubble microneedle preparation techniques could significantly increase the drug load of microneedles,providing the advantage of microinvasion.

To analyze simulated patient studies and their developmental trajectory, a comprehensive review was conducted using VOS viewer software. PubMed and CNKI databases were searched for 4 164 articles related to simulated patients. By creating keyword clouds and comparison tables, the current status and development trends of simulated patient studies at home and abroad were analyzed, and visual analysis was conducted based on these findings. Additionally, the analysis encompassed various metrics such as the number of published articles, journals, authors, and institutions involved. The findings reveal that the simulated patient studies focus on education, examination, and communication. Chinese studies on simulated patients initially demonstrated an upward trend but followed with a decline, whereas English studies have exhibited a steady upward trajectory. The application of simulated patients spans diverse fields including diagnostics, internal medicine, surgery, and medical practitioner exams, thereby greatly contributing to the advancement of medical education. It is anticipated that the number of simulated patient studies will continue to surge in the upcoming years.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Diabetic kidney diseases （DKD） is one of the main microvascular complications of diabetes. According to the available studies， the initial factor of DKD is glomerular injury. However， in recent years， more and more studies have confirmed that renal tubular injury plays a key role in the development of DKD. Taking renal tubules and their interstitium as therapeutic targets has become a new idea for the treatment of DKD. Traditional Chinese medicine （TCM） can treat renal tubular injury in DKD via multiple pathways， targets， and links， demonstrating significant therapeutic effect and slight side effects. According to the etiology and pathogenesis of DKD， doctors differentiate different syndromes such as deficiency of both Qi and Yin， deficiency of spleen and kidney Yang， and Qi deficiency and blood stasis and then adopt the therapies of nourishing kidney and strengthening essence， clearing heat and eliminating dampness， tonifying Qi and nourishing yin and so on， which have shown significant effect in the treatment of renal tubular injury in DKD. This paper summarizes the experimental studies about the treatment of renal tubular injury in DKD by TCM compound prescriptions， as well as the effective parts， extracts， and active ingredient of Chinese herbal medicines. Chinese herbal medicines and their derivates can regulate Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）/antioxidant response element （ARE）， transforming growth factor-β₁ （TGF-β₁）/Smads and other signaling pathways to treat renal tubular injury from resisting oxidative stress， inhibiting apoptosis of renal tubular epithelial cells， and blocking renal tubular epithelial-mesenchymal transformation. With this review， we hope to provide a theoretical basis for the development and clinical application of new drugs for renal tubular injury in DKD.

Blended teaching method has become an important part of the educational reform. Massive open online courses (MOOC) combined with flipped classroom in pediatrics education consists of online courses, flipped classroom and online communication. Students are promoted to engage in education actively through the online homework, tests, discussions and examinations, thus reaching the best teaching effect. This paper aims to introduce the establishment and accomplishments of this blended teaching method in Pediatrics education in Fudan University.

Objective:To observe any effect of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors.Methods:The walking of twenty-five stroke survivors was quantified using a gait analysis system. They walked barefoot, wearing a half palm ankle-foot orthosis and wearing a hollow-heel ankle-foot orthosis. Walking speed, step frequency, duration of the swing phase on the healthy and affected sides, risk of falling and Timed Up and Go (TUG) test times were recorded and analyzed.Results:The average gait frequency when wearing the hollow-heel ankle-foot orthosis was significantly faster than that in the other two conditions. The gait asymmetry coefficient was significantly different when the subjects wore the hollow-heel ankle-foot orthosis compared with walking barefoot. Compared with being barefoot, the average TUG time was significantly shorter when wearing either orthosis and the risk of falling was significantly less. The fall risk was significantly lower when wearing the hollow-heel orthosis compared to the half palm orthosis.Conclusion:Wearing either ankle-foot orthosis can significantly correct the gait of stroke survivors and lower their risk of falling, with better effect when wearing the hollow-heel ankle-foot orthosis.

Objective:To investigate the clinical, genetic, and clonality related aspects of individuals with Richter transformation (RT) .Methods:From January 2019 to December 2021, 18 RT patients with diagnoses at the First Affiliated Hospital of Nanjing Medical University (Pukou CLL center) were retrospectively examined. The immunoglobin heavy variable (IGHV) gene usage and IGHV-D-J rearrangement pattern of diagnosed CLL/SLL and transformed diffuse large B-cell lymphoma (DLBCL) were compared to determine the clonality relatedness. To investigate the risk factors of RT, Clinical and laboratory data from patients with newly diagnosed CLL/SLL and transformed DLBCL were gathered.Results:The median age of RT was 56.5 (41-75) years old. 17 patients transformed to DLBCL and 1 transformed to Hodgkin lymphoma (HL) . Of 17 individuals who had DLBCL transformation, 15 had CLL/SLL-related clonality and 2 had unrelated clonality. Next-generation sequencing (NGS) analysis of 11 paired initially diagnosed treatment-naive CLL/SLL and RT DLBCL found that EGR2、TP53 and NOTCH1 were among the most frequently mutated genes both in treatment-naive CLL/SLL and in RT DLBCL. In several cases, specific mutations were gained or lost throughout RT, indicating clonal evolution. Among 10 patients before exposure to BTK inhibitors before RT, four patients acquired BTK mutation. The aforementioned mutations should be considered high-risk variables for transformation; in addition, TP53 and EGR2 mutations could be linked to a poor prognosis following RT in patients receiving a cocktail of new medicines.Conclusion:Most RT DLBCL patients in our center are clonality related (15/17, 88.2% ) and we recommend all qualified centers to evaluate clonality relatedness of RT DLBCL patients. There was some variability in the mutational landscape between DLBCL that had undergone a transformation and initially diagnosed, treatment-naive CLL/SLL. The underlying molecular mechanism of RT needs more research.

Objective:To explore the effect of different teaching modes in medical students′education of cardiopulmonary resuscitation(CPR)skills.Methods:One hundred and fifty college students were randomly allocated to classroom teaching group(G1=50), problem-based learning(PBL)group(G2=50) and computer-based teaching group(G3=50)from March to December in 2019.The students′acquisition and retention of theoretical knowledge and skills were assessed before(baseline)and after the teaching(immediately), then 2 months and 6 months later.Results:One hundred and fifty college students participated in the study.Among them, 84(56.0%)were male, with an average age of 23 years old.Sixteen students(10.7%)had participated in similar CPR training.There was no significant statistical difference in the demographic characteristics of students among three groups.At four time points including baseline, after teaching(immediately), 2 months and 6 months later, there was no significant difference in the theoretical examination results among three groups( P>0.05). But after teaching, the scores of each group were improved.At the second time point(after teaching immediately), each group had the highest scores( P<0.05). Compared the scores of the second point, the ones of the third time point(2 months later after teaching)and the fourth time point(6 months later after teaching)decreased, but there was no significant difference between the two time points( P<0.05). There was no significant difference in the pass rates of skill exam at the time point of baseline among three groups( P>0.05). The pass rates of G2 and G3 were significantly higher than those of G1 at 2 and 6 months later after teaching( P<0.05), but there was no significant difference between two groups.After teaching, the passing rate of each group was significantly higher than that of the baseline, and there were significant differences in the passing rates of any other time points after teaching, with the passing rate decreasing.Students′ feedback showed that all of them could clearly understand the teaching objective and accept the difficulty of the course, and PBL and computer teaching modes were more acceptable. Conclusion:PBL and computer-based teaching modes have better learning effectiveness and acceptance, which can be used as supplemental training to conventional classroom teaching or as strategies to consolidate learning.Two months may be the time point for retraining.

In 2013, Shanghai Medical College of Fudan University restarted the enrollment of the undergraduate students in directional pediatrics. To cultivate medical talents in pediatrics, a serious of educational innovations and practices have been carried out guided by competency training, including training a team of teachers with simulated teaching skills and establishing a teaching platform for simulation teaching. Medical students can practice medicine and gain experience through the risk-free simulated scenarios, that is helpful to enhance their confidence in clinical skills and communications and decrease medical errors in their future careers.