[Analysis of MTHFR gene variants in fifteen children with hyperhomocysteinemia].

The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) µmol/L and (69.96±32.88) µmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (P<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) µmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.

[The pathological characteristics and prognostic analysis of medullary thyroid microcarcinoma].

Objectives: To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). Methods: A case series studies. The clinical data of patients with medullary thyroid carcinoma (MTC) diagnosed by postoperative pathology and with complete follow-up data who were initially treated in Tianjin Medical University Cancer Hospital from January 2013 to December 2019 were retrospectively analyzed. There were a total of 170 cases, including 70 males and 100 females, aged (49.7±12.3) years old. Among them, there were 61 patients with MTMC. They were divided into group A (with a maximum tumor idameter of ≤0.5 cm, n=13) and group B (with a maximum tumor diameter >0.5~≤1.0 cm, n=48) based on whether the maximum diameter of the tumor was >0.5 cm. Analysis was conducted on their pathological results and prognosis. Results: Among the MTC, MTMC accounted for 26.4% (61/231) with 26 males and 35 females aged Mï¼»Q1，Q3ï¼½51.0 (41.0, 59.0) years. Among the MTMC patients, 57.4% (35/61) were in stage Ⅰ, 16.4% (10/61) were in stage Ⅲ, and 26.2% (16/61) were in stage Ⅳ. For MTMC with a maximum diameter of≤0.5 cm and a maximum diameter of >0.5-≤1.0 cm, there was no statistically significant difference between the two groups in terms of gender, age, mixed cancer, invasion of glandular lobes, multifocal, central lymph node metastasis, lateral neck lymph node metastasis rate and other pathological characteristics(both P>0.05). In terms of prognosis, the recurrence free survival time of MTMC patients was 83.1 (68.0, 97.0) months. Among them, structural tumor recurrence occurred in 5 patients (8.2%) after surgery, and 1 patient (1.6%) died. The expected 5-year and 10-year survival rates were 93.4% and 89.0%, respectively. There was no statistically significant difference in recurrence free survival time among MTMC patients, MTC patients with a maximum diameter of >1.0-≤2.0 cm, and MTC patients with a maximum diameter of >2.0 cm (all P>0.05). Conclusion: MTMC has strong invasiveness, and although the prognosis of most MTMCs is relatively good, the risk of long-term recurrence and death is still high.

[Impact of hyperoxia on the phenotype of pulmonary artery smooth muscle cells].

Objective: To investigate the influence of varied oxygen (O2) concentration environments on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMC) and the mechanism of pulmonary hypertension. Methods: Primary rat PASMC were isolated and cultured through the process of enzymatic digestion. Following identification, the stable passaged PASMC were subjected to a 6-hour incubation in sealed containers with normal O2 content (group C) and relative O2 content comprising 55% (group H55), 75% (group H75), and 95% (group H95). mRNA and protein expression of α-Actin (α-SMA), smooth muscle 22α (SM22α), osteopontin (OPN), and matrix metalloproteinase-2 (MMP-2) were measured using real-time quantitative PCR and western blot analysis. Results: The H55 group displayed no significant difference from the C group in terms of mRNA and relative protein expression levels for α-SMA, SM22α, OPN, and MMP-2 (all P>0.05). On the other hand, groups H75 and H95 exhibited a reduction in mRNA and relative protein expression of α-SMA and SM22α, along with an increase in mRNA and relative protein expression of OPN and MMP-2 when compared with both the C and H55 groups (all P<0.05). The H95 group showed a higher relative mRNA expression of MMP-2 as compared to the H75 group (P<0.05). Conclusions: Oxygen concentration environments of 75% or higher can serve as the foundation for the pathogenesis of pulmonary hypertension, essentially by inducing a phenotypic transformation in PASMC towards adopting a robust secretory function. This induction is contingent upon the concentration of oxygen present.

[Genetic variation of sequences of partial mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit 1 (pnad1) and pnad5 genes of Toxascaris leonina isolates from foxes and dogs in Jiuquan City of Gansu Province].

OBJECTIVE: To investigate the genetic variations of Toxascaris leonina isolates from different hosts in Jiuquan City, Gansu Province. METHODS: The mitochondrial sequences of partial mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit 1 (pnad1) and pnad5 of eleven T. leonina isolates from domestic dogs, foxes and pet dogs in Jiuquan City, Gansu Province, were amplified using PCR, and the amplification product was sequenced. The genetic variations of pnad1 and pnad5 genes in T. leonina isolates were analyzed. RESULTS: The sequences of T. leonina pnad1 and pnad5 genes measured 530 bp and 550 bp in size, respectively. The nucleotide sequence homology was 99.4% to 100.0% for T. leonina pnad1 gene and 99.5% to 99.8% for T. leonina pnad5 gene, and the sequences of T. leonina pnad1 and pnad5 genes shared 99.2% to 99.9% and 99.1% to 99.9% with corresponding sequences of known T. leonina isolates. In addition, there were 19 and 24 polymorphic sites detected in the sequences of T. leonina pnad1 and pnad5 genes, with 10 and 9 haplotypes, haplotype diversity of 0.982 and 0.964 and nucleotide diversity of 0.039 4 and 0.034 2, respectively. Phylogenetic analysis based on pnad1 and pnad5 gene sequences showed that the eleven T. leonina isolates and known T. leonina isolates were clustered into the same branch with a random distribution, which were close to the branch where Toxocara canis was clustered, and far from the branch where other Ascaris species were clustered. CONCLUSIONS: There is a minor genetic variation in pnad1 and pnad5 genes of T. leonina isolates from different hosts in Jiuquan City, Gansu Province, and the pnad1 gene is more suitable as a molecular marker than pnad5 gene for analysis of genetic variations in T. leonina.

[Correlation between dyslipidemia and the risk of papillary thyroid carcinoma].

Objective: To investigate the correlation between dyslipidemia and the risk of papillary thyroid carcinoma (PTC). Methods: A case-control study was conducted. PTC patients diagnosed by pathology in Tianjin Medical University Cancer Institute and Hospital from April 2014 to August 2019 were enrolled as the experimental group, and healthy controls in the physical examination center at the same time were also enrolled as the control group. The demographic data and blood lipid parameters of the subjects were collected. Multivariate logistic analyses were used to assess the correlation between dyslipidemia and the risk of PTC. Results: A total of 2 000 cases of PTC were enrolled, with a mean age of (42±12) years, including 1 419 females (71.0%) and 581 males (29.0%). There were 4 524 cases in the control group, with a mean age of (42±9) years, including 3 311 females (73.2%) and 1 213 males (26.8%). There was no statistically difference in age and gender between the two groups (both P>0.05). Compared with the control group, triglyceride (TG) [(1.7±1.1) vs (1.4±1.0) mmol/L, P<0.001] and low-density lipoprotein (LDL) [(2.9±0.8) vs (2.8±0.7) mmol/L, P=0.015] increased in peripheral blood of PTC patients, while high-density lipoprotein (HDL) [(1.3±0.4) vs (1.4±0.3) mmol/L, P<0.001] decreased, but the difference was not statistically significant in total cholesterol (TC) [(4.9±1.0) vs (4.9±0.8) mmol/L, P=0.172]. After adjusting for age and gender, increase of TC (OR=1.20, 95%CI: 1.06-1.34, P=0.003), TG (OR=1.73, 95%CI: 1.55-1.94, P<0.001), LDL (OR=1.21, 95%CI: 1.08-1.36, P=0.001), LDL/HDL (OR=1.77, 95%CI: 1.56-2.02, P<0.001) and decrease of HDL (OR=3.15, 95%CI: 2.78-3.58, P<0.001) were the related factors of PTC. Conclusions: Compared with the control group, patients with PTC have higher level of TG and LDL and lower level of HDL. Dyslipidemia is an important factor related to the risk of PTC.

[Analysis of the application of radiotherapy facility construction project evaluation standard in health management institutions].

Objective: To investigate the application of GBZ/T 220.2-2009 "The Specification of Radiological Protection Assessment for Occupational Hazard in Construction Project-Part 2: Radiotherapy Facility" in health management institutions, and to understand the scientificity, practicability and problems existing in the implementation of the standard. Methods: The method of multistage stratified sampling and questionnaire survey were used to collect the standard application status among 96 radiological health managers who had participated in the evaluation of radiotherapy facility construction projects in 6 provinces and cities from November 2020 to April 2021. A descriptive statistical analysis method was used to analyze the basic information of the survey object, the knowledge of the standard, the publicity and implementation of the standard. Results: The radiological health management personnel mainly came from health supervision agencies (62.5%, 60/96) , and 86.5% (83/96) were engaged in the pre-evaluation of radiotherapy device construction project and the approval and supervision of control effect evaluation. The awareness rate and training rate of radiological health managers on GBZ/T 220.2-2009 were 88.5% (85/96) and 31.3% (30/96) , respectively. 89.6% (86/96) managers thought it could meet the needs of radiotherapy facility construction project approval or supervision. 49.0% (47/96) of managers believed that the standard needed to be revised. Conclusion: The content of GBZ/T 220.2-2009 is basically scientific and reasonable, but the publicity, implementation and training of radiological health administrator still need to be strengthened. It is suggested to revise some clauses in the standard that do not meet the requirements.

[Study of three kinds of primary immunization schedules with poliovirus vaccine].

Objective: To compare the immunogenicity of three kinds immunization programs with poliovirus vaccine. Methods: Healthy infants aged 2 months or over were selected and divided into three groups by complete randomization method. Basic immunization with Sabin inactivated poliovirus vaccine(sIPV) and bivalent oral poliovirus vaccine(bOPV) were completed. Three kinds of basic immunization procedures were 1sIPV+2bOPV,2sIPV+1bOPV and 3sIPV, respectively.Two qualified serums that before basic immunization and 28-42 days later were collected, and measured the poliovirus neutralizing antibody with microcell neutralization method. To compare the difference by analysis of variance, rank test and χ2 test. Results: After the basic immunization, 205 subjects of the positive conversion rate of poliovirus neutralizing antibodies of types Ⅰ, Ⅱ and Ⅲwere all higher than 97.00%, and the positive rates were all higher than 98.00%, the geometric mean titer (GMT) of neutralizing antibody was significantly higher than that before basic immunization in three groups.There were significant differences in the positive rate and GMT before and after basic immunization of typeⅠ, Ⅱand Ⅲ in the three (P<0.05). The highest GMT in three groups after basic immunization were all typeⅠ, followed by type Ⅲ, and the lowest in type Ⅱ. The GMT of type Ⅱin 2sIPV+1bOPV and 3sIPV groups were both higher than that in sIPV+2bOPV group. Conclution: After three kinds of basic immunization, the poliovirus neutralizing antibodies of serum were all at high levels in three groups, which could form an effective immune barrier against poliovirus. The immunogenicity of three kinds of basic immunization programs were all well, but there were certain differences of neutralizing antibodies among three kinds basic immunization programs. The immunogenicity in 2sIPV+1bOPV and 3sIPV groups against typeⅡpoliovirus were better than that in 1sIPV+2bOPV group.

[Application of hybrid surgery in the clipping of large complex paraclinoid aneurysms].

Nine patients with large complex paraclinoid aneurysms were treated by hybrid surgery in the Second Affiliated Hospital of Zhejiang University between January 2016 and July 2021. Intraoperative angiography was conducted for real-time evaluation of the aneurysm and its clipping efficacy. A total of 8 aneurysms were clipped under temporary proximal control with balloon occlusion. Suction decompression was simultaneously applied in 2 of these cases. After surgery, 2 patients developed symptomatic cerebral infarction, 3 patients developed transient oculomotor nerve palsy, but no patients had vision deterioration. Postoperative follow-up showed that small neck residue occurred in 1 case, but with the rest of aneurysms were completely occluded without parent artery stenosis. Hybrid surgery was proved to be advantageous in real-time assessment of aneurysm morphology and clipping efficacy. Combination of temporary proximal balloon occlusion and suction decompression technique can help in reducing the difficulty of aneurysm exposure and remodeling, thereby improving the outcome and decreasing the complications.

[Correlations of serum TgAb and TPOAb and clinicopathological features of PTC in children and adolescents].

Objective: To analyze the correlations between serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and clinicopathological features in children and adolescents with papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was conduced on the clinicopathological data of children and adolescents (age≤21 years old) with PTC admitted to Tianjin Medical University Cancer Hospital from 2011 to 2019, and then, we used χ2 test or Fisher's exact probability test to compare the differences in clinicopathological characteristics between groups with different TgAb and TPOAb status and multivariate logistic regression model analysis to evaluate independent predictors of cervical lymph node metastasis. Results: A total of 304 patients, including 89 males and 215 females, aged 5-21 years (median age 19 years), were enrolled in this study. The comparison between groups with different TgAb and TPOAb status showed that there were significant differences in gender, preoperative thyroglobulin (Tg) level, primary tumor location, number of primary tumors and maximum tumor diameter (all P<0.05), which suggested that TgAb+group (n=81) and TPOAb+group (n=84) had relatively better primary tumor characteristics. Patitents with TgAb+and TPOAb+were more common in females and their preoperative Tg level was mostly within the normal range, and there were significant differences in primary tumor location, number of primary tumors and maximum tumor diameter between TgAb+and TgAb-(223 cases) groups (all P<0.05). There was significant difference in the maximum tumor diameter between TPOAb+and TPOAb-(220 cases) groups (P<0.05). Analysis of risk factors for cervical lymph node metastasis showed that independent risk factors for central lymph node metastasis were maximum tumor diameter>2 cm (OR=2.84, 95%CI: 1.59-5.07, P<0.001) and extra-thyroid extension (OR=0.32, 95%CI: 0.17-0.60, P<0.001), and independent risk factors for lateral neck lymph node metastasis included age≤14 years old (OR=0.34, 95%CI: 0.18-0.67, P=0.002), preoperative Tg+(OR=2.16, 95%CI: 1.10-4.24, P=0.026) and maximum tumor diameter>2 cm (OR=3.99, 95%CI: 2.33-6.82, P<0.001). Conclusion: It is recommended to test routinely serum TgAb and TPOAb before surgery in children and adolescents with PTC. Preoperative Tg+, age≤14 years, maximum tumor diameter>2 cm, and extra-thyroid extension are risk factors for cervical lymph node metastasis.

Beneficial effect of melatonin administration on the function of frozen-thawed rat testicular grafts.

BACKGROUND: Spermatogonia in testis is sensitive to the cytotoxicity of chemotherapy agents. Cryopreservation of testicular tissue may offer fertility restoration in young male cancer survivors. OBJECTIVE: To investigate the effect of melatonin on the survival of testicular grafts following cryopreservation and transplantation. MATERIALS AND METHODS: Wister rats were randomly allocated into three groups: control group; saline group (cryopreservation + autograft + saline); and melatonin group (cryopreservation + autograft + melatonin). Malondialdehyde (MDA) content, glutathione peroxidase (GPx) activity and superoxide dismutase (SOD) activity were assessed on day 7 after autograft transplantation. At day 30, graft recovery, spermatogonia per round tubule, and serum testosterone concentration in grafts were measured. RESULTS: Melatonin significantly diminished MDA content, enhanced GPx and SOD activities. Furthermore, the recovery rate, number of spermatogonia per round tubule, and serum testosterone concentration in melatonin group was markedly higher than the saline group. CONCLUSION: Melatonin administration at 20 mg/kg is effective in improving the function of frozen and thawed rat testicular graft. The protective role of melatonin can be attributed partly to the enhanced ROS scavenging and antioxidant enzyme activities. doi.org/10.54680/fr22310110612.

[Intestinal flora polymorphisms with different lesional stages in an animal model of MAFLD].

Objective: To study the intestinal flora specific differences with different lesional stages of metabolic (disorder) associated fatty liver disease (MAFLD), namely simple steatosis and steatohepatitis, so as to provide a new direction for MAFLD-related intestinal flora transplantation and targeted therapy. Methods: Mice were fed with normal diet, methionine-choline deficient diet (MCD) and a high-fat high-fructose diet (HFHF) for 12 weeks to construct simple steatosis and steatohepatitis models. HE and Sirius scarlet staining was performed to observe the liver pathological changes. The qPCR method was used to evaluate inflammation and liver fibrosis factors. A fully automatic biochemical analyzer was used to detect changes in liver transaminase and blood lipids. 16S rRNA sequencing method was used to observe the intestinal flora differences in the feces of each group of mice. The comparison of means between two groups was performed by t-test, and the comparison of means between multiple groups was performed by one-way analysis of variance. Kruskal-Wallis rank sum test was used for non-normally distributed data. Results: NAFLD scores were determined with pathological sections (HE and Sirius scarlet staining) of mice liver, which showed that the inflammation and liver fibrosis scores of the MCD and HFHF groups were 2.12 ± 0.18 and 1.06 ± 0.24, and 2.22 ± 0.16 and 0.46 ± 0.10, respectively. The degree of liver inflammation and fibrosis was significantly higher in the MCD than the HFHF group (P < 0.001 and P < 0.01). Lipid deposition was higher in the HFHF than the MCD group (P < 0.001), and the scores were 2.36 ± 0.17 and 1.60 ± 0.24 respectively. Simultaneously, the inflammatory [tumor necrosis factor-A (TNF-a), chemokine factor-2 (CXCL-2)] and hepatic fibrosis indicators [vascular smooth muscle actin alpha (a-SMA) and connective tissue growth factor (CTGF)] had confirmed the above-mentioned results at the transcription level. Moreover, the intestinal flora diversity was reduced (P < 0.05) in the MCD group than the HFHF group, and the Simpson and Shannon index were 0.31 ± 0.10 and 0.42 ± 0.05, and 2.03 ± 0.33 and 1.70 ± 0.28, respectively, and the differences were significant between different intestinal flora groups. The levels of Desulfovibrio, Odoribacter, and Roseburia flora were significantly increased in the HFHF than the MCD group, and the levels of Faecalibaculum, Parasutterella, Alipis, Butyricimonas_virosa, Turicibacter_sp, and Romboutsia_ilealis were significantly increased in the MCD than the HFHF group, and the difference was statistically significant (P < 0.05). Conclusion: There are significant differences in intestinal flora diversity between simple steatosis and steatohepatitis models. Therefore, clarifying the difference between the two may provide a new direction for the stage manner treatment of MAFLD.

[Research progress on the human health risks assessment of radionuclides in water environment].

The quality of the water environment is one of the most important factors that can directly affect the health of human beings and other non-human species. The levels of the radionuclides in water environment are the key indicator while assessing the quality of water environment. Recently, with the development of the nuclear energy in China, the public people have paid a focus attention on the levels and the health risks of the radionuclides. This paper introduced the sources, the health effects, the health risk assessment methods and the current status of the health risk assessment study about the radionuclides, in order to provide basis for the health risk assessment of radionuclides in water environment and the protection of human health.

Damage of Granusola and Stroma Cells Exposed to Mouse Ovarian Tissue Cryopreservation: Potential Mechanism of Ovarian Injury.

BACKGROUND: Several obstacles must be overcome before ovarian tissue cryopreservation can be used as a standard procedure. OBJECTIVE: To carry out a morphologic and functional study of the effect of cryopreservation on mouse follicles and stroma cells. MATERIALS AND METHODS: Female mice were divided into three groups (control, fresh graft and cryopreserved graft). Ultrastructural features of follicles and stroma cells were evaluated using transmission electron microscopy. After autologous transplantation, micro-vessel densities of grafts were examined. RESULTS: Vacuoles in granulosa cells and stromal cells are significantly greater than that of oocytes. The microvessel density of fresh grafts is significantly higher than that in frozen-thawed grafts. CONCLUSION: Granusola and stroma cells, rather than oocytes, are vulnerable to cryoinjury. Injuries to granulosa cells and stromal cells could be the critical part of ovarian damage caused by cryopreservation.

[Indications, selection, and effect of flap application in repairing scar carcinoma in the lower leg and ankle].

Objective: To explore the indications, selection, and effect of flap application in repairing scar carcinoma in the lower leg and ankle. Methods: A retrospective cohort study was conducted. From June 2008 to December 2018, six male patients with scar carcinoma in the lower leg and ankle were treated in Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, aged 48-64 years, with the area of lesion ranging from 3 cm×2 cm to 15 cm×6 cm. After extended resection, the defect area ranged from 8 cm×5 cm to 22 cm×9 cm, with tissue of tendon or bone exposed. Free anterolateral thigh perforator flap, latissimus dorsi myocutaneous flap, or pedicled sural neurovascular flap was selected to repair the wound according to the location of wound in the lower extremity, selection of operation position, the location of the anastomotic vessels in the recipient area, and whether there was good skin and soft tissue available in the lower leg. The size of flap was 11 cm×8 cm-26 cm×10 cm. The donor site of free flap or myocutaneous flap was closed directly by suturing in 5 cases, and the donor site of pedicled flap was repaired with full-thickness skin graft in 1 case. The blood supply and survival of flap, quality of skin graft survival, and complication were observed postoperatively. During the follow-up period, the recurrence and metastasis of scar carcinoma, and the appearance and function of donor and recipient sites were observed. Results: All the patients completed the operation successfully, all the transplanted flaps survived with good blood supply, and the skin graft in one donor site survived well. The wounds in the donor and recipient sites of all the patients healed well without infection, effusion, or dehiscence, etc. All the patients were followed up for 1-5 years. No local recurrence or distant metastasis of scar carcinoma was found. The quality of the transplanted flaps was good. The shape of the recipient area was quite good, and the function of the affected limb was fine. The appearance of the donor area was good without dysfunction. Conclusions: Flap transplantation is suitable for the patients with tendon and bone exposure after the excision of scar carcinoma in the lower leg and ankle. The flap can be selected according to the location of scar carcinoma, operation position, the location of anastomotic vessels in the recipient area, and whether there is good skin and soft tissue available in the lower leg. The free anterolateral thigh perforator flap or latissimus dorsi myocutaneous flap is an ideal choice for repair, which can be obtained in a large area, and the donor site can be directly sutured without affecting the function.

Different effects of probiotics and antibiotics on the composition of microbiota, SCFAs concentrations and FFAR2/3 mRNA expression in broiler chickens.

AIMS: The aims of this study were to investigate the effects of probiotics and antibiotics on microbial composition, short chain fatty acids (SCFAs) concentration and free fatty acid receptor 2/3 (FFAR2/3) expression in boiler chickens. METHODS AND RESULTS: A total of 150 1-day-old male broilers were randomly allocated into three groups, control (CON) group, probiotics (PB) group and antibiotics (ATB) group. Results indicated that PB improved the average body weight from 1 to 21 days and feed intake from 21 to 42 days (P < 0·05), while ATB improved the feed efficiency from 1 to 42 days (P < 0·05). Based on 16s rRNA sequencing, PB treatment increased the amount of kingdom bacteria, and the relative abundance of the main bacteria including acetate and butyrate producing bacteria of phylum Firmicutes, family Ruminococcaceae and genus Faecalibacterium. ATB treatment also increased the relative abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, however, it introduced some pathogenic bacteria, such as bacteria of family Rikenellaceae and Enterobacteriaceae. Gas chromatography and mass spectrometry (GC-MS) assay revealed that PB increased acetate and butyrate concentrations at both 21 and 42 days, and propionate at 42 days in the colorectum. Moreover qRT-PCR analysis showed PB treatment significantly activated the FFAR2/3 mRNA expressions. On the contrast, ATB treatment lowered the colorectal propionate at 21 days, and decreased acetate, propionate and butyrate concentrations at 42 days, accompanied with decreased FFAR2/3 mRNA expressions. CONCLUSIONS: Compared to the CON birds, an enriched SCFAs producing bacteria with higher SCFAs contents and activated FFAR2/3 expressions are prominent features of PB birds. However, antibiotics treatment plays the reverse effect compared to PB treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study brings a significant idea that less SCFAs concentration may be another reason why the antibiotics inhibit the immune system development and immunity of the body.

[Feasibility and safety of new simplified left bundle branch area pacing via nine-partition method].

Objective: To investigate the efficacy and safety of left bundle branch area pacing (LBBaP) with the new simplified approach (nine-partition method). Methods: A total of 118 patients with clinical indications and received pacemaker implantation from December 1, 2018 to December 31, 2019 in Beijing Anzhen Hospital were enrolled. LBBaP was performed with the nine-partition method (in the right anterior oblique 30° position, the ventriculogram was divided into nine partitions and the initial implant sites were located in the lower base 1/3 partitions). In X-ray image, the 3830 lead is located in the left bundle branch area, the unipolar pacing QRS wave is in the form of right bundle branch block, and the peak time from stimulation to left ventricular activation<90 ms is defined as successful operation. The clinical characters, such as the methods of venipuncture, electrode parameters, operation duration, fluoroscopy duration, the peak time from stimulation to left ventricular, pacemaker types, surgical success rate, complications, and immediate postoperative ECG parameters were collected. The patients were followed up after the operation, and the electrode parameters and postoperative complications were recorded. Results: This study is a retrospective study. There were 62 (52.5%) male patients in this cohort, the average age was (65.9±13.4) years old,and there were 49(41.5%) sick sinus syndrome, 6(5.1%) abnormal sinus node and atrioventricular node simultaneously, 63(53.4%) atrioventricular block, 26(22.0%) atrial fibrillation, 20(16.9%) cardiomyopathy; the baseline duration of QRS was (109.21±39.03) ms. Successful LBBaP was achieved in 109 patients with"nine-partition method"and the success rate was 92.4%; 104 patients (95.5%) were axillary vein puncture, 5 (4.6%) were subclavian vein puncture; the operation duration was (80.3±23.0) min, the fluoroscopy duration was (12.29±5.13) min; the QRS duration after LBBaP was (116.36±18.11) ms. The threshold of the left bundle branch (LBB) lead was (0.92±0.63) V, the R wave amplitude was (10.60±5.04) mV and the impedance was (798.71±194.90) Ω. In 1 V pacing, the peak time from stimulation to left ventricular activation was (67.91±12.15) ms, and in 5 V pacing was (67.52±12.45) ms; 1 case (0.9%) with a single-chamber pacemaker implanted, 106 cases (97.3%) with dual-chamber pacemaker and 2 cases (1.8%) with three-chamber pacemakers. There were no hematomas, pneumothorax, hemothorax, electrode dislocation, infection, and capsular hemorrhage and other serious surgery-related complications during the operation. A total of 97 patients (89.0%) were followed up for (6.21±2.90) months. The electrode parameters of all patients were stable and no complications observed. Conclusions: The LBBaP with nine-partition method is a simple, safe and effective physiological pacing approach. However, its long-term effect still needs to be further verified.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.