Heart failure is the terminal stage of various cardiovascular diseases and a leading cause of death. For a long time, natural medicines have been used to treat heart failure（HF） with remarkable effects. In this paper, the Traditional Chinese Medicine compound patents in the national patent database were mined, common Traditional Chinese Medicines for the clinical treatment of HF were selected, and the single active ingredient contained in them was analyzed, which provided some valuable tips for the development of drugs for the treatment of heart failure.

Childhood household dysfunction(CHD)is a common adverse childhood experience,which brings the heavy physical and mental afflictions to children and adolescents.Trauma-focused cognitive behavioral therapy(TF-CBT)is an evidence-based psychotherapy that helps children and adolescents who have experienced childhood trauma with traumatic memories.It aims to enhance the coping abilities of CHD children and adolescents,thereby improving the negative effects caused by trauma and effectively reducing psychological burden.TF-CBT can effectively improve post-traumatic stress disorder,emotional and behavioral problems,and family function in children and adolescents with CHD.It is recommended to conduct high-quality original research in the future,develop targeted TF-CBT intervention plans based on potential predictive factors,adopt a combination of online and offline methods,and construct TF-CBT interventions suitable for the Chinese CHD population to meet the mental health service needs of CHD children and adolescents.

Objective:To study the clinical manifestations, genetic profiles and treatment of Kagami-Ogata syndrome (KOS).Methods:A neonate admitted to our hospital was genetically diagnosed of KOS from amniocentesis sampling. The phenotype, genotype and treatment of the neonate were analyzed. Multiple databases were searched using key words including "Kagami-Ogata syndrome", "14q32 microdeletion syndrome", "coat-hanger ribs", "paternal uniparental disomy (pUPD)(14) " from the inception of the databases to Jan. 23th 2023. The clinical features, genotype and treatment of patients from the literature were summarized.Results:The neonate in our hospital was born at 30 weeks gestational age with a birth weight of 2 035 g. Prenatal ultrasound indicated overgrowth, bilateral fetal renal pelvis dilatation (FRPD), dilatation of intestines in lower abdomen, clenched hands with overlapping fingers and polyhydramnios. After birth, the neonate showed progressively worsening respiratory distress, distinct facial features (small jaw, short neck, flat nasal bridge, upward-facing nostrils, small and malformed ears with auricular deformity and narrow external auditory canals), bell-shaped thorax, diastasis recti and abnormal posture (overlapping fingers, clenched fists), as well as feeding difficulties, recurrent fever and dependence of respiratory support. Whole exome sequencing (WES) revealed a 268.2Kb deletion (101034306_101302541) in 14q32.2 region on both the neonate and the mother and the father was otherwise normal. The prognosis was poor and the parents refused further treatment. The neonate died at one month of age after two days of palliative care. A total of 36 articles were identified in the literature review, including 78 KOS cases with complete clinical data (a total of 79 cases adding our case).The primary clinical manifestations included distinctive facial and thoracic abnormalities (79/79, 100%), polyhydramnios (71/75, 94.7%), feeding difficulties (55/63, 87.3%), abdominal wall defects (57/72, 79.2%), joint contractures (39/70, 55.7%) and dependence of respiratory support (29/56, 51.8%). Long-term follow-up revealed 86.8% (59/68) experienced physical, movement and intellectual development delay, 39.7% (25/63) died or gave up treatments within five years. Genetic testing showed pUPD in 44 cases (55.7%), maternal deletions in 23 cases (29.1%), epimutations in 8 cases (10.1%) and unreported variations in 4 cases (5.1%).Conclusions:KOS is a genetic imprinting disorder affecting multiple organs. Prenatal screening can detect abnormalities such as polyhydramnios. Specific clinical signs, radiological findings and 14q32 gene analysis are helpful for the diagnosis of the disease.

High quality continuing medical education is important to ensure the clinical competence of doctors. However, the current continuing medical education of general practitioners has some problems, such as low motivation to participate in and poor training effect. We tried a new model of continuing medical education to deal with these problems. In this new model, position competence improvement is the aim, online group learning is the main method, individualized learning goals are developed and results are evaluated in verifiable ways.

Objective:To analyze the risk factors for premature infants with hemodynamically significant patent ductus arteriosus (hs-PDA) requiring surgical treatment, and to explore the indications for surgical treatment in premature infants with hs-PDA.Methods:A nested case-control study was conducted.The data of premature infants with gestational age<30 weeks who were diagnosed with hs-PDA in the Neonatal Intensive Care Unit of Peking Union Medical College Hospital from January 2007 to May 2020 were analyzed retrospectively.The hs-PDA patients treated surgically were included in the operation group.The hs-PDA patients of the same gestational age and gender who were not treated surgically were taken as the control group.The ratio of the case number between the operation and control groups was 1∶2.The clinical data during pregnancy, at birth and after birth of premature infants were compared between the 2 groups.The measurement data were tested by the independent sample t test or Mann- Whitney U test.The classification and enumeration data were compared by the Fisher′ s exact probability method.The risk factors for premature infants with hs-PDA requiring surgical treatment were analyzed by the conditional Logistic regression method. Results:A total of 182 premature infants with hs-PDA were enrolled in the study, including 10 in the operation group and 20 in the control group.The patients underwent PDA ligation 30.5(22.7, 37.0) d after birth, and the median preo-perative invasive ventilation duration was 9.7(17.5, 27.2) d. Compared with the control group(20 cases), the preterm infants in the operation group had a lower birth weight [(891.5±118.0) g vs.(1 054.4±230.2) g, t=2.091], a wider arterial duct diameter [3.2(2.8, 4.0) mm vs.2.0(2.0, 3.0) mm, Z=-3.300], and longer invasive ventilation duration [25.0(18.7, 38.2) d vs.3.0(1.0, 7.5) d, Z=-3.688]. Besides, the operation group applied the pulmonary surfactant for more times [2(1, 3) times vs.1(1, 2) times, Z=-2.440], and inhaled a higher concentration of oxygen on the 14 th day after birth [29(25, 36)% vs.21(21, 29)%, Z=-2.358] than the control group.Moreover, compared with the control group, the operation group took longer to achieve adequate enteral feeding [48.2(51.5, 63.5) d vs.42.5(23.5, 48.0) d, Z=2.789], and gained a higher maximum vasoactive inotropic score (VIS) [3.0(0, 3.5) points vs.0(0, 0) points, Z=-2.630]. The difference in all the above-mentioned indicators between the 2 groups was statistically significant (all P<0.05). Univariate Logistic regression analysis showed that the arterial duct diameter, application times of the pulmonary surfactant, the maximum VIS score, and the time taken to achieve sufficient enteral feeding were all related to the need for surgical treatment of hs-PDA in the operation group (all P<0.05). Multivariate Logistic regression analysis revealed that the invasive ventilation duration ( OR=0.747, 95% CI: 0.560-0.998, P=0.048) was an independent risk factor for hs-PDA premature infants requiring surgical treatment. Conclusions:The factors related to the need for surgical treatment in preterm infants with hs-PDA include a wide arterial duct diameter, multiple applications of the pulmonary surfactant, a high concentration of inhaled oxygen on the 14 th day, and the long time to achieve sufficient enteral feeding.The independent risk factor for the surgical treatment in hs-PDA children is the long invasive ventilation duration.

Objective: To understand the prevalence and associated factors of spinal curvature in children and adolescents in the Yangtze River Delta Region and to provide reference and help for the prevention and intervention of spinal curvature in children and adolescents. Methods: From September to November 2021, 8 246 middle school students in Anhui, Jiangsu, Shanghai, and Zhejiang provinces in the Yangtze River Delta Region were selected by stratified cluster sampling for spinal curvature assessment and questionnaire survey. Results: The detection rate of spinal curvature in middle school students in the Yangtze River Delta was 8.46 %. Girls (9.82%) were significantly higher than boys (7.20%)( χ 2=18.25, P <0.01), and students from urban area (10.77%) was significantly higher than that of suburban area (4.94%)( χ 2=86.75, P <0.01). Junior high school students (6.65%) were significantly lower than high school students (10.34%)( χ 2=36.26, P <0.01). Logistic regression analysis showed that urban area( OR= 2.58, 95%CI =1.72-3.86), time usage of electronic equipment ≥ 3 h/d( OR=1.61, 95%CI =1.14-2.29), break between near work for more than 1 h ( OR=1.42, 95%CI =1.01-1.97) and outdoor activity <2 h/d( OR=1.84, 95%CI =1.26-2.69) were positively correlated with the occurrence of spinal curvature( P <0.05). Conclusion The detection rate of spinal curvature in middle school students in the Yangtze River Delta is relatively high, which is related to time spent on screen, near work and outdoor activity. Education and guidance should be strengthened to reduce the detection rate of spinal curvature.

Objective: To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. Methods: Patients diagnosed with AIS after CC during 2007–2021 were identified by computerized databases at Women’s Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. Results: Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. Conclusion CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.

Metabolic homeostasis is a basic function necessary for the survival of the organism. α₁-acid glycoprotein (AGP) is an acute phase protein with a glycosylation degree of up to 45%. It has high affinity and low capacity. Although the biological role of AGP is not fully understood, it has been proven that it can regulate immunity and metabolism, and play an important role in transporting drugs and maintaining capillary barrier function. In this review, the structural characteristics, biochemical characteristics and the regulation of AGP expression were reviewed, with emphasis on the regulatory role of AGP in metabolism, suggesting that AGP may be a potential key factor in metabolic pathways, which provides a new research direction for metabolic diseases.