BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

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OBJECTIVE: To observe the characteristics of changes in non-invasive hemodynamic parameters in neonates with septic shock so as to provide clinical reference for diagnosis and treatment. METHODS: A observational study was conducted. The neonates with sepsis complicated with septic shock or not admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Shantou University Medical College were enrolled as the study subjects, who were divided into preterm infant (< 37 weeks) and full-term infant (≥ 37 weeks) according to the gestational age. Healthy full-term infants and hemodynamically stable preterm infants transferring to NICU after birth were enrolled as controls. Electronic cardiometry (EC) was used to measure hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI), before treatment in the septic shock group, at the time of diagnosis of sepsis in the sepsis without shock group, and before the discharge from the obstetric department or on the day of transferring to NICU in the control group. RESULTS: Finally, 113 neonates with complete data and parental consent for non-invasive hemodynamic monitoring were enrolled, including 32 cases in the septic shock group, 25 cases in the sepsis without shock group and 56 cases in the control group. In the septic shock group, there were 17 cases at the compensated stage and 15 cases at the decompensated stage. There were 21 full-term infants (20 cured or improved and 1 died) and 11 premature infants (7 cured or improved and 4 died), with the mortality of 15.62% (5/32). There were 18 full-term infants and 7 premature infants in the sepsis without shock group and all cured or improved without death. The control group included 28 full-term infants and 28 premature infants transferring to NICU after birth. Non-invasive hemodynamic parameter analysis showed that SV, SVI, CO and CI of full-term infants in the septic shock group were significantly lower than those in the sepsis without shock group and control group [SV (mL): 3.52±0.99 vs. 5.79±1.32, 5.22±1.02, SVI (mL/m²): 16.80 (15.05, 19.65) vs. 27.00 (22.00, 32.00), 27.00 (23.00, 29.75), CO (L/min): 0.52±0.17 vs. 0.80±0.14, 0.72±0.12, CI (mL×s^-1×m^-2): 40.00 (36.67, 49.18) vs. 62.51 (56.34, 70.85), 60.01 (53.34, 69.68), all P < 0.05], while SVR and SVRI were significantly higher than those in the sepsis without shock group and control group [SVR (kPa×s×L^-1): 773.46±291.96 vs. 524.17±84.76, 549.38±72.36, SVRI (kPa×s×L^-1×m^-2): 149.27±51.76 vs. 108.12±12.66, 107.81±11.87, all P < 0.05]. MAP, SV, SVI, CO and CI of preterm infants in the septic shock group were significantly lower than those in the control group [MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 38.55±10.48 vs. 47.46±2.85, SV (mL): 2.45 (1.36, 3.58) vs. 3.96 (3.56, 4.49), SVI (mL/m²): 17.60 (14.20, 25.00) vs. 25.50 (24.00, 29.00), CO (L/min): 0.32 (0.24, 0.63) vs. 0.56 (0.49, 0.63), CI (mL×s^-1×m^-2): 40.01 (33.34, 53.34) vs. 61.68 (56.68, 63.35), all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 1 082.88±689.39 vs. 656.63±118.83, SVRI (kPa×s×L^-1×m^-2): 126.00±61.50 vs. 102.37±11.68, both P > 0.05]. Further analysis showed that SV, SVI and CI of neonates at the compensation stage in the septic shock group were significantly lower than those in the control group [SV (mL): 3.60±1.29 vs. 4.73±1.15, SVI (mL/m²): 19.20±8.33 vs. 26.34±3.91, CI (mL×s^-1×m^-2): 46.51±20.34 vs. 61.01±7.67, all P < 0.05], while MAP, SVR and SVRI were significantly higher than those in the control group [MAP (mmHg): 52.06±8.61 vs. 48.54±3.21, SVR (kPa×s×L^-1): 874.95±318.70 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 165.07±54.90 vs. 105.09±11.99, all P < 0.05]; MAP, SV, SVI, CO and CI of neonates at the decompensated stage in the septic shock group were significantly lower than those in the control group [MAP (mmHg): 35.13±6.08 vs. 48.54±3.21, SV (mL): 2.89±1.17 vs. 4.73±1.15, SVI (mL/m²): 18.50±4.99 vs. 26.34±3.91, CO (L/min): 0.41±0.19 vs. 0.65±0.15, CI (mL×s^-1×m^-2): 43.34±14.17 vs. 61.01±7.67, all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 885.49±628.04 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 114.29±43.54 vs. 105.09±11.99, both P > 0.05]. CONCLUSIONS Full-term infant with septic shock exhibit a low cardiac output, high vascular resistance hemodynamic pattern, while preterm infant with septic shock show low cardiac output and normal vascular resistance. At the compensated stage the hemodynamic change is low output and high resistance type, while at the decompensated stage it is low output and normal resistance type. Non-invasive hemodynamic monitoring can assist in the identification of neonatal septic shock and provide basis for clinical diagnosis and treatment.
Humans ; Shock, Septic/physiopathology* ; Infant, Newborn ; Hemodynamics ; Female ; Male ; Case-Control Studies ; Infant, Premature

The Major Principles of the Five Elements is a collection of Yin-Yang and Five Elements theories in the middle ancient period of China.The Xiangshu model of Yin-Yang and Five Elements is the basic paradigm to clarify the world and its existence."Constitution"and"Function"are a pair of important categories used in ancient philosophy to describe the relationship be-tween the nature and function of ontology.Based on the two temporal and spatial rhythms of the Heluo Heaven and Earth Five Elements view and the Jiugong Bafeng spatiotemporal view constructed by the Xiangshu model,The Major Principles of the Five Elements explains the connotation and characteristics of traditional medical constitution and function,aiming to elucidate the evolution process of the path-ogenesis of constitution and function,guide the dialectical thinking of constitution and function,and flexibly select and combine drug properties and flavors to harmonize the human constitution and function.This paper provides a unique perspective and method for ex-plaining the concept and connotation of constitution and function in traditional Chinese medicine by glimpsing the gradual changing way of thinking in traditional medicine from the Pre-Qin period to the Tang Dynasty.

Objective:By observing the effects of Calycosin on the proliferation and migration of human renal cancer 769-P cell, to explore the possible molecular mechanism of Calycosin against renal cancer.Methods:769-P cell were cultured with different concentrations of Calycosin [0, 12.5, 25, 50, 100, 200 μmol/L, dissolved in Dimethyl sulfoxide (DMSO)], and the effects of different concentrations of Calycosin on the viability of 769-P cell was detected by CCK8 method. The 769-P cell treated with 200 μmol/L Calycosin were used as the Calycosin group, and the 769-P cell treated with DMSO were used as the control group. The cell colony formation assay and cell scratch assay were used to detect the effects of Calycosin on the proliferation and migration of 769-P cell, respectively. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the effect of Calycosin on the expression of miRNA-1246 and chemokine receptor-4 (CXCR4) in 769-P cell. Western blotting method was used to detect the effects of Calycosin on the expression of CXCR4 and extracellular signal-regulated kinase (ERK) pathway proteins in 769-P cell. Measurement data were expressed as mean ± standard deviation ( ± s), and one-way ANOVA was used for comparison between multiple groups, while t-test was used for comparison between two groups. Results:After cultured with 0, 12.5, 25, 50, 100, and 200 μmol/L of Calycosin, the absorbance values of renal cancer 769-P cell were 0.99 ± 0.06, 0.74 ± 0.07, 0.60 ± 0.03, 0.55 ± 0.05, 0.40 ± 0.06, 0.21 ± 0.04, respectively; compared with 0 μmol/L, the Calycosin could reduce the survival rate of 769-P cell ( P<0.05). The number of clones of 769-P cell in the control group and the Calycosin group was 109.80 ± 13.19 and 60.66 ± 11.22, respectively, and the number of clones of the 769-P cell in the Calycosin group was decreased, the difference was statistically significant ( t=5.67, P<0.01). The relative migration rates of 769-P cell in the control group and the Calycosin group were (43.13 ± 3.82)% and (14.27 ± 3.25)%, respectively, after the 769-P cell were treated with Calycosin, the cell migration ability was weakened ( t=5.71, P<0.05). The relative expression levels of miRNA-1246 in 769-P cell of the control group and the Calycosin group was 1.03 ± 0.12 and 6.99 ± 1.84, respectively, and the relative expression levels of CXCR4 mRNA was 7.17 ± 2.96 and 0.98 ± 0.06, respectively, showed that Calycosin can up-regulate the expression of miRNA-1246 in 769-P cell ( t=3.24, P<0.01), and down-regulate the expression of CXCR4 mRNA ( t=4.18, P<0.01). Compared with the control group, the Calycosin could down-regulate the expression of CXCR4 protein and ERK pathway protein in 769-P cell. Conclusion:Calycosin can inhibit the proliferation and migration of renal cancer 769-P cell, and its mechanism may be related to up-regulating the expression of miRNA-1246 and blocking the CXCR4/ERK pathway.

Objective To explore the relationship between long non-coding RNA(lncRNA)non-coding repressor of nuclear factor of activated T cells(NRON),long non-coding RNA small NF90-associated RNA(snaR)and the prognosis of triple negative breast cancer(TNBC).Methods From February 2018 to February 2020,100 TNBC patients accepted by our hospital were collected,and their tumor and adjacent tissues were taken during surgery.Based on the 3-year follow-up prognosis,they were separated into a good prognosis group(72 cases)and a poor prognosis group(28 cases).Real-time quantitative fluorescent PCR(RT-qPCR)method was applied to detect the expression levels of lncRNA NRON and lncRNA snaR in tumor tissue and adjacent tissues.Pearson method was applied to analyze the correlation between lncRNA NRON and lncRNA snaR in tumor tissue of TNBC patients.Multivariate Cox regression was applied to analyze the prognostic factors of TNBC patients.Receiver operating characteristic(ROC)curve was applied to analyze the prognostic value of lncRNA NRON and lncRNA snaR expression levels in tumor tissue of TNBC patients.Results Compared with adjacent tissues,the level of lncRNA NRON in tumor tissues of TNBC patients obviously decreased(1.01±0.10 vs 0.65±0.08,P＜0.001),while the level of lncRNA snaR obviouslv increased(1.03±0.13 vs 2.42±0.30,P＜0.001).The expression levels of lncRNA NRON and lncRNA snaR were related to TNM staging and tumor differentiation(P＜0.05).Compared with the good prognosis group,the level of lncRNA NRON in tumor tissue of TNBC patients in poor prognosis group obviously decreased(0.69±0.09 vs 0.55±0.05,P＜0.001),while the level of lncRNA snaR obviously increased(2.28±0.26 比 2.78±0.40,P＜0.001).Pearson method analysis showed that there was a negative correlation between lncRNA NRON and lncRNA snaR expression levels in tumor tissue of TNBC patients(r=-0.617,P＜0.001).Multivariate Cox regression analysis showed that lncRNA NRON was a protective factor for the prognosis of TNBC patients(P＜0.05),LncRNA snaR was a risk factor for the prognosis of TNBC patients(P＜0.05).The combination of lncRNA NRON and lncRNA snaR expression levels in predicting better prognosis in TNBC patients than lncRNA snaR alone(Zcombination-lncRNA snaR=3.200,P=0.001).Conclusion The level of lncRNA NRON is down-regulated and lncRNA snaR level is obviously up-regulated in tumor tissues of TNBC patients,they are related to the prognosis of TNBC patients and may be biomarkers for evaluating TNBC prognosis.

As the main product of anaerobic or aerobic glycolysis,lactic acid has long been considered to be only the metabolic waste of this process,but now researches have are gradually revealing that lactic acid,as an important signaling molecule,plays a key immune regulatory role by acting on lactic acid transporters,lactate receptors and intracellular direct sensors in immune cells.In chronic inflammatory diseases,lactic acid helps maintain a pro-inflammatory environment that encourages immune cells to remain at the site of inflammation.In the event of infection,lactic acid impairs host immunity.In the tumor microenvironment(TME),the increase in lactic acid production and the resulting TME acidification promote tumor growth and invasion,and inhibit the body's immune response to tumor antigens.This review focuses on the recent research progress on the role of lactic acid in immune regulation.

While biologic agents are widely used in rheumatology practice，its side effects become apparent and are brought into focus.Biologic agents associated vasculitis are drug induced vasculitis which are induced by biologic agents.It is one of the main and severe immunological side effects by biologic agents.Its pathogenesis is unclear.And the clinical characteristic is various.Tumor necrosis factor-α inhibitors are most likely to cause vasculitis，and leukocytoclastic vasculitis is the most common one.The diagnosis of biologicagents associated vasculitis is difficult and should be paid attention in clinical practice.The biologic agents withdrawal which induced vasculitis is the critical treatment，while steroids and immune-suppressants should be given if necessary.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.