Clinical phenotypic and genotypic analysis of 5 pediatric patients with β-ketothiolase deficiency / 中华儿科杂志

Objective: To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Primary abdominal cocoon syndrome, situs inversus totalis and bilateral cryptorchidism: a case report / 中华泌尿外科杂志

This paper reviewed the clinical data of a patient with primary abdominal cocoon syndrome, situs inversus totalis and bilateral cryptorchidism admitted to our hospital in March 2021, and discussed the clinical characteristics of the disease based on the literature. This case is relatively rare, and all three diseases involve congenital abnormalities that may lead to developmental disorders in the embryo. The clinical manifestations of abdominal cocoon syndrome lack of specificity, preoperative diagnosis is difficult, often accompanied by partial dysplasia, so it is necessary to improve the awareness of preoperative differential diagnosis.

Effect of chronic restraint stress on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice / 解剖学报

Objective To explore the effect of chronic restraint stress (CRS) on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice. Methods Forty eight male C57BL/6 mice were randomly divided into control groups (control), model groups (CRS) and fluoxetine(FLX) drug intervention groups (CRS+FLX), 16 for each group. The mice of the CRS group were subjected to 3 weeks chronic restraint stress. The mice of CRS + FLX group were treated with fluoxetine by intraperitoneal injection 30 minutes before restraint stress from the day 8 to day 21.

Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide / 解剖学报

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC + LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC + LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P<0.0001); In the open field test, compared with the NS group, the total distance (P < 0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P< 0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P < 0.05), the distance of activities in the central area (P < 0.001) and the time of in the central area (P < 0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P<0.05), nNOS (P < 0.001), and eNOS (P < 0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P < 0.05, nNOS P < 0.01 and eNOS P < 0.01). Conclusion Inhibiting the expression of TRPV4 can improve the anxiety-like behavior, and this process may be related to anti-oxidative stress.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Effect of galangin on hypoxia-inducible factor-1α-mediated epithelial mesenchymal transformation in gastric cancer cells / 中国药理学通报

Aim To investigate the effect of galangin(GLA) on gastric cancer in hypoxic microenvironment. Methods The gastric cancer SGC-7901 cell line was induced with CoCl

Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles / 中华妇产科杂志

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

Clinical characteristics and follow-up analysis of 12 patients of acute phosphine poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the clinical characteristics of patients with acute phosphine poisoning, and to follow up and evaluate the prognosis of patients. Methods: In May 2022, 12 patients with phosphine poisoning by respiratory inhalation in Beijing Chao-Yang Hospital of Capital Medical University were analyzed. The patients were treated with symptomatic support therapy. Three months later, patients were re-evaluated the symptoms of poisoning, pulmonary function and magnetic resonance imaging (MRI) of the brain to understand the prognosis of the phosphine poisoning. Results: The main symptoms of 12 patients were respiratory and central nervous system symptoms with hypoxia. The symptoms of poisoning improved after treatment. Follow-up found that the patients had different degrees of residual symptoms. Pulmonary function showed increased airway resistance. Airway challenge test was positive in some patients. MRI of the head of some patients showed small ischemic focus in bilateral frontal lobes. Conclusion: Acute phosphine poisoning may cause persistent damage to the respiratory system and central system, and residual symptoms after 3 months.

Evaluation of right ventricular function using two-dimensional speckle tracking echocardiography and analysis of the risk factors for right ventricular dysfunction in patients with silicosis / 中华劳动卫生职业病杂志

Objective: To evaluate the right ventricular function using two-dimensional speckle tracking echocardiography (2-D STE) and analyze the associated risk factors of right ventricular dysfunction in patients with silicosis. Methods: All 104 patients with silicosis treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from May 2021 to September 2022 were enrolled in this study in October 2022. The clinical information of patients such as general data, arterial blood gas analysis and pulmonary function test were collected. The right ventricular function of patients was evaluated by 2-D STE-derived right ventricular free wall longitudinal strain (RVFWLS) and conventional echocardiographic-derived parameters, including right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'), respectively. Based on their RVFWLS, the patients were divided into right ventricular dysfunction group and normal right ventricular function group. Risk factors for right ventricular dysfunction in patients with silicosis were analyzed using binary logistic regression analysis. Results: A total of 104 silicosis patients were enrolled, with aneverage age (65.52±11.18) years old, among whom including 57 cases diagnosed with stage Ⅰ/Ⅱ silicosis and 47 cases diagnosed with stage Ⅲ silicosis. 26 (25.00%) patients concurrent right ventricular dysfunction. The abnormal rates of RVFAC, TAPSE and S' in patients were 16.35% (17 cases), 21.15% (22 cases) and 6.73% (7 cases), respectively. The RVFAC and TAPSE in right ventricular dysfunction group were lower than those in normal right ventricular function group, and the incidence of pulmonary arterial systolic pressure ≥36 mmHg was higher than that in normal right ventricular function group (P<0.05). Logistic regression analysis showed that arterial partial pressure of oxygen (OR=0.932, 95%CI: 0.885-0.981, P=0.007) was the protective factor, and the forced expiratory volume in 1 second (FEV(1)) /forced vital capacity (FVC) ratio<70% (OR=5.484, 95%CI: 1.049-28.662, P=0.044) and stage Ⅲ silicosis (OR=6.343, 95%CI: 1.698-23.697, P=0.007) were the risk factors for silicosis patients concurrent right ventricular dysfunction. Conclusion: The incidence of right ventricular dysfunction is higher in patients with stage Ⅲ silicosis than that in patients with stage Ⅰ/Ⅱ silicosis. Using 2-D STE can help the early detection of silicosis with right ventricular dysfunction. Hypoxemia, airflow limitation and the stage Ⅲ silicosis are the risk factors for silicosis patients concurrent right ventricular dysfunction.

Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease / 中华儿科杂志

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study / 中华妇产科杂志

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

Current status of public health system in Guangdong-Hong Kong-Macao Greater Bay Area and improvement suggestion / 中华流行病学杂志

Guangdong-Hong Kong-Macao Greater Bay Area (GBA) has three public health systems under different systems, which plays an important role in the construction of the public health system in China. Further strengthening the construction of the public health system in the GBA will play an important reference role in the optimization and upgrade of China's public health system in the future. Based on the key consulting project of "research on the strategy of the modern public health system and capacity building in China" by Chinese Academy of Engineering, this paper deeply analyzes the current status and existing problems of public health system construction in GBA and suggests to improve and innovate the mechanisms of collaborative prevention and control of public health risks, resource coordination and joint research and result sharing, information sharing and exchange, personnel training and team building in order to comprehensively improve the capacity of public health system in GBA, and promote the construction of Healthy China.

BCS1Neonatal growth retardation and lactic acidosis initiated by novel mutation sites in L gene / 中华预防医学杂志

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.

The impact of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year outcome in patients with premature coronary heart disease: results of a prospective, multicenter, observational cohort study / 中华心血管病杂志

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.

Forsythiaside B inhibits cerebral ischemia/reperfusion-induced oxidative stress injury in mice via the AMPK/DAF-16/FOXO3 pathway / 南方医科大学学报

OBJECTIVE@#To study the protective effect of forsythiaside B (FB) against cerebral oxidative stress injury induced by cerebral ischemia/reperfusion (I/R) in mice and explore the underlying mechanism.@*METHODS@#Ninety C57BL/6 mice were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) model group, and low-, medium and highdose (10, 20, and 40 mg/kg, respectively) FB groups. The expression levels of MDA, ROS, PCO, 8-OHdG, SOD, GSTα4, CAT and GPx in the brain tissue of the mice were detected using commercial kits, and those of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 were detected with Western blotting. Compound C (CC), an AMPK inhibitor, was used to verify the role of the AMPK pathway in mediating the therapeutic effect of FB. In another 36 C57BL/6 mice randomized into 4 sham-operated group, MCAO model group, FB (40 mg/kg) treatment group, FB+CC (10 mg/kg) treatment group, TTC staining was used to examine the volume of cerebral infarcts, and the levels of ROS and SOD in the brain were detected; the changes in the protein expressions of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 in the brain tissue were detected using Western blotting.@*RESULTS@#In mice with cerebral IR injury, treatment with FB significantly reduced the levels of ROS, MDA, PCO and 8-OHdG, increased the activities of antioxidant enzymes SOD, GSTα4, CAT and GPx, and enhanced phosphorylation of AMPK and FOXO3 and DAF-16 protein expression in the brain tissue (P < 0.01). Compared with FB treatment alone, the combined treatment with FB and CC significantly reduced phosphorylation of AMPK and FOXO3, lowered expression of DAF-16 and SOD activity, and increased cerebral infarction volume and ROS level in the brain tissue of the mice (P < 0.01).@*CONCLUSION@#FB inhibits oxidative stress injury caused by cerebral I/R in mice possibly by enhancing AMPK phosphorylation, promoting the downstream DAF-16 protein expression and FOXO3 phosphorylation, increasing the expression of antioxidant enzymes, and reducing ROS level in the brain tissue.

The application of intraoperative neurophysiological monitoring in selective dorsal neurotomy for primary premature ejaculation: a prospective single-center study / 亚洲男科学杂志(英文版)

Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.

Standard Process for Palliative Sedation in Peking Union Medical College Hospital / 中国医学科学院学报

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.

Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain based on oxycodone hydrochloride extended-release tablet.@*METHODS@#A total of 60 patients with lung cancer pain were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases). In the control group, oxycodone hydrochloride extended-release tablet was given orally, 10 mg a time, once every 12 hours. On the basis of the treatment in the control group, Miao medicinal crossbow acupuncture therapy was applied once every other day in the observation group. The treatment of 14 days was required in the two groups. Before and after treatment, the numerical rating scale (NRS) score, number of break-out pain and Karnofsky performance status (KPS) score were observed in the two groups. The equivalent oxycodone consumption and rate of adverse reactions were recorded, the analgesic effect was evaluated in the two groups.@*RESULTS@#Compared before treatment, the NRS scores and number of break-out pain were decreased while the KPS scores were increased after treatment in the two groups (P<0.01). After treatment, the NRS score and number of break-out pain in the observation group were lower than the control group (P<0.01), the KPS score in the observation group was higher than the control group (P<0.05). The equivalent oxycodone consumption of whole course and the rate of adverse reactions i.e. constipation, drowsiness, nausea and vomiting in the observation group were lower than the control group (P<0.05). The analgesic effect rate was 93.1% (27/29) in the observation group, which was superior to 63.3% (19/30) in the control group (P<0.05).@*CONCLUSION@#On the basis of oxycodone hydrochloride extended-release tablet, Miao medicinal crossbow acupuncture therapy as adjuvant treatment can effectively relieve the pain degree, reduce the number of break-out pain and improve the health status and quality of life in patients with lung cancer pain, enhance the efficacy of medication and reduce its adverse reactions.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.