Research progress in the etiology of hepatitis type E virus / 中华肝脏病杂志

Hepatitis type E virus (HEV) is a significant infectious zoonotic disease that causes hepatitis E. The disease is primarily transmitted via the fecal-oral route through contaminated water or food and is transmissible between species and genera. The causative agent for the disease is the hepatitis type E virus, which is a member of the Hepadnaviridae family and a single-stranded RNA virus. Its 7.2 kb genome mainly contains three open reading frames (ORFs): ORF1 encodes a non-structural polyprotein that mediates viral replication and transcription; ORF2 encodes a capsid protein and free antigen that induce neutralizing antibodies; ORF3 partially overlaps with ORF2 and encodes a small multifunctional protein involved in virion formation and release. HEV has a unique dual life cycle: it is excreted into feces in the form of naked virions but circulates in the blood in the form of "quasi-enveloped" particles. The two kinds of virus particles adsorb and penetrate the host cell in distinct ways, then internalize and decapsulate to replicate the genome, thereby producing more virion and releasing it outside the cell to mediate the virus's spread. This paper reviews the morphological characteristics, genome structure, encoded proteins, and function of HEV virus-like particles in order to provide a theoretical basis for basic research and comprehensive disease prevention and control.

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.

Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment / 中华妇产科杂志

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

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.

Whole exome sequencing analysis and prenatal diagnosis in children with neurodevelopmental disorders / 中华预防医学杂志

To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.

Optimization of production process of Aeromonas veronii CA07 strain inactivated vaccine / 中国生物制品学杂志

@#Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

Inhibitory effect of astragalus membranaceus injection on apoptosis and autophagy induced by enterovirus 71 / 中国生物制品学杂志

@#Objective To investigate the effect of astragalus membranaceus（AM）injection on apoptosis and autophagy of human gastric epithelial cell line（GES⁃1）induced by enterovirus 71（EV71）. Methods GES⁃1 cells were cultured in vitro and divided into infected group（EV71 infected at a MOI of 3 and control group（no virus infected）. The morpho⁃logical changes of EV71 infected cells were observed by inverted microscope. The level of VP1 in GES⁃1 cells infected with EV71 was detected by Western blot；CCK⁃8 assay was used to detect the viability of GES⁃1 cells infected with EV71；Nuclear staining with DAPI was used to observe the morphological changes of nuclear apoptosis infected with EV71. GES⁃1 cells were divided into control group（without virus infection），infection group and AM intervention group with final concentration of 1，2. 5，5 and 10 μg／mL，respectively. Western blot was used to detect the effect of AM intervention on the expression of apoptosis⁃related proteins Caspase⁃3，PARP and autophagy⁃related proteins LC3 and P62 in GES⁃1 cells infected withEV71. CCK⁃8 method was used to detect the effect of AM intervention on the viability of GES⁃1 cells infected with EV71. Results GES⁃1 cells were round，shrunken with nuclear pyknosis and uneven size；VP1 level increased（t = 41. 56，P < 0. 01），cell viability decreased（t = 19. 07，P < 0. 01），Caspase⁃3 and PARP proteins were cut off（t = 35. 29 and 3. 648， P < 0. 01 and 0. 021 8，respectively），LC3Ⅱ／LC3Ⅰ ratio increased（t = 10. 16，P = 0. 000 5）and P62 protein was degraded（t = 68. 68，P < 0. 01）；AM inhibited the degradation of Caspase⁃3，PARP and P62 proteins induced by EV71 （t = 52. 66，59. 60 and 40. 22，respectively，each P < 0. 01）and increased the ratio of LC3Ⅱ／LC3Ⅰ（t = 5. 521，P = 0. 005 3），andreducedtheinhibitoryeffectofEV71ontheviabilityofGES⁃1cells（t =4. 420，P =0. 0115）. Conclusion EV71 infection induced apoptosis of GES⁃ 1 cells and AM intervention inhibited EV71 induced apoptosis by inhibiting EV71 induced autophagy.

A pair of new isoflavonoid enantiomers from Dalbergia benthamii Prain / 药学学报

Thirteen isoflavones were separated and purified from an ethanol extract of the rhizome of Dalbergia benthamii Prain by using silica gel, Sephadex LH-20, recrystallization et al. Their structures were identified by physicochemical properties and spectral analysis such as MS, 1D/2D-NMR as dalbergibenthamin (1), butesuperin A (2), xanthocercin A (3), butesuperin B (4), di-O-methylalpinum isoflavone (5), 2′-deoxgisoaunculutin (6), robustone (7), 4′-hydroxy-5,7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (8), formononetin (9), 6″-O-rhamnosyldaidzin (10), 3′,4′-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (11), derrubone dimethyl enter (12), and derrubone (13). Compound 1 is a pair of new isoflavonoid enantiomers, compound 12 is a new natural product and compounds 1-7 and 10-13 were obtained from D. benthamii Prain for the first time. In vitro cytotoxic activities of the compounds were explored by MTS testing with HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines. Results show that compound 8 significantly inhibited cellular proliferation. The IC50 of compound 8 in A-549 and SW480 cells was 16.68 ± 0.19 and 15.21 ± 0.60 μmol·L-1.

Expression of CTRP9 in serum of patients with diabetic retinopathy and diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and correlation of C1q/tumor necrosis factor related protein 9(CTRP9)levels in the serum of patients with different stages of diabetic retinopathy(DR)and diabetic macular edema(DME).METHODS: A total of 135 patients with type 2 diabetes who were admitted to Gansu Provincial Hospital from April 2021 to April 2022 were selected as the experimental group. According to the results of non-mydriatic fundus photography, they were divided into non-DR(NDR)group(n=45), non-proliferative DR(NPDR)group(n=45), proliferative DR(PDR)group(n=45); according to the results of optical coherence tomography, DR patients were divided into DME group(n=51), non-DME group(n=39). In addition, other 45 healthy subjects who matched the age and sex of the experimental group were selected as normal control group. The clinical data and biochemical index test results of subjects in each group were recorded and compared, the correlation between serum CTRP9 level and other biochemical indexes was analyzed, and the risk factors affecting the occurrence of DR and DME were explored.RESULTS: There were significant differences in serum CTRP9 levels among subjects in normal control group, NDR group, NPDR group and PDR group(P<0.001), and normal control group > NDR group > NPDR group > PDR group. There was significant difference in serum CTRP9 level between DME group and non-DME group(P<0.001), and non-DME group > DME group. Spearman rank correlation analysis showed that the level of serum CTRP9 in DR patients was negatively correlated with the course of diabetes(rs=-0.251, P<0.05), the level of serum CTRP9 in DME patients was negatively correlated with fasting blood glucose(FBG)(rs=-0.370, P<0.05)and glycosylated hemoglobin(HbA1c)(rs=-0.421, P<0.05). Logistic multivariate regression analysis showed that the course of diabetes(OR=1.194, 95%CI: 1.068～1.335,P=0.002)and the level of serum CTRP9(OR=0.936, 95%CI: 0.907～0.966,P<0.001)were risk factors for DR. The level of serum CTRP9 was a risk factor affecting the occurrence of DME(OR=0.838, 95%CI: 0.778～0.903, P<0.001).CONCLUSION: The reduction of CTRP9 level is a risk factor for the occurrence of DR and DME, which may be of great significance to the risk assessment of both DR and DME.

Effect of Elevated Basal LH on IVF-ET Outcomes in Patients with Polycystic Ovary Syndrome / 中山大学学报(医学科学版)

ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.

Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives / 中国中药杂志

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Research progress of Codonopsis Radix and prediction of its Q-markers / 中国中药杂志

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.

Effects of Platycodonis Radix-Curcumae Rhizoma on oral nanoparticle uptake and in vitro inhibition against breast cancer metastasis / 中国中药杂志

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

Cardiac Structural and Functional Features in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction:A Study Based on Propensity Score Matching / 中国医学科学院学报

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.

The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017 / 中国实验血液学杂志

OBJECTIVE@#To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients.@*METHODS@#The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively.@*RESULTS@#A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival.@*CONCLUSION@#In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

Relationship between skeletal muscle mass index and metabolic phenotypes of obesity in adolescents / 中国当代儿科杂志

OBJECTIVES@#To study the relationship between skeletal muscle mass index (SMI) and metabolic phenotypes of obesity in adolescents, and to provide a basis for the prevention and control of adolescent obesity and related metabolic diseases.@*METHODS@#A total of 1 352 adolescents aged 12 to 18 years were randomly selected by stratified cluster sampling in Yinchuan City from October 2017 to September 2020, and they were surveyed using questionnaires, physical measurements, body composition measurements, and laboratory tests. According to the diagnostic criteria for metabolic abnormalities and the definition of obesity based on the body mass index, the subjects were divided into four metabolic phenotypes: metabolically healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity. The association between SMI and the metabolic phenotypes was analyzed using multivariate logistic regression.@*RESULTS@#The SMI level in the metabolically unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity groups was lower than that in the metabolically healthy normal weight group (P<0.001). Multivariate logistic regression analysis showed that after adjusting for gender and age, a higher SMI level was a protective factors for adolescents to develop metabolic unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity phenotypes (OR=0.74, 0.60, and 0.54, respectively; P<0.001).@*CONCLUSIONS@#Increasing SMI can reduce the risk of the development of metabolic unhealthy/obesity.

Research Progresses of Tri-Allelic Patterns in Autosomal STR in Forensic DNA Analysis / 法医学杂志

Tri-allelic pattern in autosomal STR is a common abnormal typing phenomenon in forensic DNA analysis, which brings difficulties and uncertainties to the evaluation of the evidence weight in actual cases. This paper reviews the types, formation mechanism, occurrence frequency, genetic pattern and quantitative evaluation of evidence of the tri-allelic pattern in autosomal STR in forensic DNA analysis. This paper mainly explains the formation mechanism and genetic patterns based on different types of tri-allelic pattern. This paper also discusses the determination of tri-allelic pattern and the quantitative method of evidence evaluation in paternity testing and individual identification. This paper aims to provide references for scientific and standardized analysis of this abnormal typing phenomenon in forensic DNA analysis.