Objective:To compare the teaching effect of basic medical integrated courses and clinical medical integrated courses based on organ system with the traditional teaching model based on discipline,so as to provide theoretical reference for training medical talents.Methods:The program of integration of basic medical courses and clinical medical courses was formulated.The current clinical medical students who participated in the medical licensing examination were selected as the research objects under the three teaching models of basic and clinical medical integrated courses,clinical medical integrated courses,and discipline-based courses.The students'scores of comprehensive basic medicine,comprehensive clinical medicine,and medical licensing examination were analyzed to preliminarily evaluate the implementation effect of the integrated teaching model of basic medicine and clinical medicine.Result:There was no significant difference in the examination scores of students under the three teaching modes.Conclusion:The organ system-based integrated teaching model has no significant effect on students'academic performance in the short term.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Early screening for neonatal jaundice has always been essential to neonatal health care. In recent years, there have been advancements and updates in the methods and equipment employed for early screening of neonatal jaundice, including visual assessment, icterometer, point-of-care testing of serum bilirubin, jaundice screening utilizing smartphone applications, and end-tidal carbon monoxide detection. This article reviews the relevant research and progress associated with the methods above, aiming to offer a reference and guidance for scientific research and clinical practices.

Objective:To explore the relevance between secondary retroperitoneal infection, as well as the outcomes, and the approach of intensive care unit (ICU) admission for the patients suffered from acute pancreatitis.Methods:Patients with acute pancreatitis admitted to the ICU of the Second Affiliated Hospital of Anhui Medical University from January 2013 to July 2022 were retrospectively analyzed. According to ICU admission approaches, the patients were divided into the emergency group (first admission or transferred from the emergency department) and the delayed group (transferred from the general wards due to disease evolution). Patients were also divided into retroperitoneal infection group and non-retroperitoneal infection group according to whether retroperitoneal infection was accompanied. Patients' baseline data including gender, age, underlying diseases, laboratory test indicators, acute physiology and chronic health evaluationⅡ score (APACHEⅡ), sequential organ failure assessment (SOFA), computed tomography severity index (CTSI), bedside index of severity in acute pancreatitis (BISAP), and acute complications were collected. Univariate and multivariate logistic regression was used to analyze the risk factors of retroperitoneal infection in patients with acute pancreatitis.Results:A total of 271 patients with acute pancreatitis were enrolled, including 95 cases in the emergency group and 176 cases in the delayed group. The cohort included 71 cases with and 200 cases without retroperitoneal infection development. The incidence of retroperitoneal infection and the 30-day mortality of patients in the delayed group, which was observed with a significantly longer ICU stay (days), [(15.4±21.3) vs. (8.6±10.8), P<0.05], were significantly higher than those in the emergency group [retroperitoneal infection incidence rate: 31.82% (56/176) vs.15.79%(15/95), 30-day mortality: 13.64%(24/176) vs. 4.21%(4/95), both P<0.05]. Univariate Logistic analysis showed significant differences in diabetes, APACHEⅡ, SOFA, CTSI and BISAP score, urea nitrogen, creatinine, blood calcium, D-D dimer, peritoneal puncture catheter drainage and ICU transferred from general wards due to disease evolution between the retroperitoneal infection group and the non-retroperitoneal infection group. Multivariate Logistic regression analysis showed that diabetes, SOFA score, CTSI score, peritoneal puncture catheter drainage and transfered from general wards to ICU due to disease evolution were independent risk factor for retroperitoneal infection in acute pancreatitis patients[odds ratio were 3.379, 1.150, 1.358, 3.855, 2.285, respectively]. Conclusions:Acute pancreatitis patients in ICU transferred from general wards are more likely to develop retroperitoneal infection, and have a higher risk of mortality and a longer ICU stay. Delayed admission to ICU, diabetes, SOFA score, CTSI score and peritoneal puncture catheter drainage are independent risk factors for retroperitoneal infection in patients with acute pancreatitis.

Objective:To discuss the clinical characteristic and treatment of laryngeal cysts in infants. Methods:The clinical data of 19 patients diagnosed with laryngeal cysts in Department of Otolaryngology, Sichuan Provincial Maternity and Child Health Care Hospital from November 2017 to April 2023 were retrospectively analyzed. Results:All of the 19 patients were diagnosed as laryngeal cysts, with clinical manifestations included respiratory distress, inspiratory dyspnea, difficulty in feeding and low and weak crying, etc. All of them were cured after surgical treatment. Conclusion:Misdiagnosis and missed diagnosis of laryngeal cysts are prone to occur in infants and young children. After diagnosis, patients should undergo early surgical treatment to remove airway obstruction and improve ventilation.
Pregnancy ; Infant ; Child ; Humans ; Female ; Child, Preschool ; Retrospective Studies ; Laryngeal Diseases/surgery* ; Airway Obstruction/surgery* ; Laryngoscopy ; Cysts/surgery* ; Dyspnea/surgery*

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

OBJECTIVE To qualitatively analyze the chemical constituents from Tianzhi granules and their constituents absorbed into blood， and to provide reference for elucidating pharmacodynamic material basis of Tianzhi granules. METHODS UPLC-ESI-Q-TOF-MS/MS was adopted. The analysis was performed on an Agilent Eclipse Plus C18 column with mobile phase consisted of 0.5% formic acid solution-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min； the column temperature was 40 ℃ ；the injection volume was 10 μL. Mass spectrometry was applied for the qualitative analysis under positive ionization mode and ESI ion source. Data were collected with MS-DIAL4.60， and then chemical constituents of the extract from Tianzhi granule （by 0.5% methanol） were analyzed by comparing with relevant literature， SciFinder， PubChem， MassBank， TCMSP， TCM-ID and other databases. The blank serum， administered serum and Tianzhi granule extract were compared to analyze the constituents absorbed into the blood. RESULTS One hundred compounds were preliminarily identified from Tianzhi granules， including 46 flavonoids， 8 organic acids， 8 alkaloids， 6 terpenes， 6 coumarins， 2 quinones， 1 steroids， 7 glycosides and 16 others. Based on it， 10 prototype constituents absorbed into blood were identified preliminarily， including genistein， melatonin A， chrysin-7-O- β-glucuronide， apigenin-7-O-glucuronide， wogonin， 6-O-methylbaicalin are flavonoids， 2-hydroxyquinoline and isonacolline are alkaloids， 7-hydroxycoumarin is coumarins，1-indanol is others. CONCLUSIONS 2-hydroxyquinoline， 7-hydroxycoumarin， genistein， melatonin A， isonocolline， chrysin-7-O-β-glucuronide， apigenin-7-O-glucuronide， wogonin and 6-O-methylbaicalin may be the pharmacodynamic material basis of Tianzhi granules.