Establishment of fetomaternal tolerance through glycan-mediated B cell suppression.

Discrimination of self from non-self is fundamental to a wide range of immunological processes1. During pregnancy, the mother does not recognize the placenta as immunologically foreign because antigens expressed by trophoblasts, the placental cells that interface with the maternal immune system, do not activate maternal T cells2. Currently, these activation defects are thought to reflect suppression by regulatory T cells3. By contrast, mechanisms of B cell tolerance to trophoblast antigens have not been identified. Here we provide evidence that glycan-mediated B cell suppression has a key role in establishing fetomaternal tolerance in mice. B cells specific for a model trophoblast antigen are strongly suppressed through CD22-LYN inhibitory signalling, which in turn implicates the sialylated glycans of the antigen as key suppressive determinants. Moreover, B cells mediate the MHC-class-II-restricted presentation of antigens to CD4+ T cells, which leads to T cell suppression, and trophoblast-derived sialoglycoproteins are released into the maternal circulation during pregnancy in mice and humans. How protein glycosylation promotes non-immunogenic placental self-recognition may have relevance to immune-mediated pregnancy complications and to tumour immune evasion. We also anticipate that our findings will bolster efforts to harness glycan biology to control antigen-specific immune responses in autoimmune disease.

Partial replacement of soybean meal with microalgae biomass on in vitro ruminal fermentation may reduce ruminal protein degradation.

The objective of this study was to evaluate the effects of partially replacing soybean meal (SBM) with algal sources on in vitro ruminal fermentation. Using 6 fermenters in a 3 × 3 replicated Latin square with 3 periods of 10 d each, we tested 3 treatments: a control diet (CRT) with SBM at 17.8% of the diet dry matter (DM); and 50% SBM biomass replacement with either Chlorella pyrenoidosa (CHL); or Spirulina platensis (SPI). The basal diet was formulated to meet the requirements of a 680-kg Holstein dairy cow producing 45 kg/d of milk with 3.5% fat and 3% protein. All diets had a similar nutritional composition (16.0% CP; 34.9% NDF; 31.0% starch, DM basis) and fermenters were provided with 106 g DM/d split into 2 portions. After 7 d of adaptation, samples were collected for 3 d of each period for analyses of ruminal fermentation at 0, 1, 2, 4, 6, and 8 h after morning feeding for evaluation of the ruminal fermentation kinetics. For the evaluation of the daily production of total metabolites and for the evaluation of nutrient degradability, samples from the effluent containers were collected daily. Statistical analysis was performed with the MIXED procedure of SAS with treatment, time, and their interactions considered as fixed effects; day, square, and fermenter were considered as random effects. Orthogonal contrasts (CRT vs. algae; and CHL vs. SPI) were used to depict the treatment effect, and significance was declared when P ≤ 0.05. Fermenters that received algae-based diets had a greater propionate molar concentration and molar proportion when compared with the fermenters fed CRT diets. In addition, those algae-fed fermenters had lower branched short-chain fatty acids (BSCFA) and isoacids (IA), which are biomarkers of ruminal protein degradation, along with lower ammonia (NH3-N) concentration and greater nonammonia nitrogen (NAN). When contrasting with fermenters fed SPI-diets, fermenters fed based CHL-diets had a lower molar concentration of BSCFA and IA, along with lower NH3-N concentration and flow, and greater NAN, bacterial nitrogen flow, and efficiency of nitrogen utilization. Those results indicate that CHL protein may be more resistant to ruminal degradation, which would increase efficiency of nitrogen utilization. In summary, partially replacing SBM with algae biomass, especially with CHL, is a promising strategy to improve the efficiency of nitrogen utilization, due to the fact that fermenters fed CHL-based diets resulted in a reduction in BSCFA and IA, which are markers of protein degradation, and it would improve the efficiency of nitrogen utilization. However, further validation using in vivo models are required.

[The association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices].

Objective: To investigate the association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices. Methods: The cirrhotic patients with esophagogastric varices diagnosed in the People's Hospital of Zhengzhou University from January 2017 to March 2023 were retrospectively collected. The patients were divided into thrombotic group and non-thrombotic group according to the presence or absence of portal vein thrombosis. The failure rate of endoscopic treatment and rebleeding rate in different periods were compared between the two groups. Receiver operating characteristic (ROC) curve was used to select the best cutoff value of gastric varicose diameter that affected total rebleeding during follow-up in both groups. The influencing factors of rebleeding within 12 and 36 months in both groups were analyzed, and the influencing factors of rebleeding within 36 months in thrombus group were further analyzed. Results: A total of 106 patients were enrolled, including 53 patients in the thrombotic group [male 37, female 16, aged 18-78 (54±13) years] and 53 patients in the non-thrombotic group [male 37, female 16, aged 27-83 (55±12) years]. The follow-up time of the two groups were (20±15) and (25±15) months, respectively. The total rebleeding rate in the thrombotic group was higher than that in the non-thrombotic group [30.2% (16/53) vs 13.2% (7/53), P˂0.05]. The rebleeding rates within 6, 12, 24 and 36 months in the thrombotic group were higher than those in the non-thrombotic group [18.9% (10/53) vs 5.7% (3/53), 18.9% (10/53) vs 5.7% (3/53), 28.3% (15/53) vs 9.4% (5/53), 30.2% (16/53) vs 11.3% (6/53), all P˂0.05]. The best cut-off value of the diameter of gastric varices that affects the total rebleeding in the two groups was 10.4 mm (10 mm was selected as the best cut-off value for the convenience of practical clinical application). Hemoglobin ˂ 85 g/L (HR=0.202, 95%CI: 0.043-0.953, P=0.043), 10 mm ˂ the diameter of GV ≤ 15 mm (HR=5.321, 95%CI: 1.161-24.390, P=0.031) and endoscopic variceal ligation combined with endoscopic tissue adhesive injection (EVL+ETAI) (HR=7.172, 95%CI: 1.910-26.930, P=0.004) were the risk factors for the first gastroesophageal variceal rebleeding within 12 months after non-urgent endoscopic treatment. EVL+ETAI (HR=3.811, 95%CI: 1.441-10.084, P=0.007) and portal vein thrombosis (HR=4.026, 95%CI: 1.483-10.932, P=0.006) were the risk factors for the first gastroesophageal variceal rebleeding within 36 months after non-urgent endoscopic treatment. The study found that, 10 mm ˂ the diameter of GV ≤ 15 mm (HR=7.503, 95%CI: 1.568-35.890, P=0.012) was the risk factor for rebleeding within 36 months in the thrombotic group. Conclusion: Portal vein thrombosis is a risk factor for rebleeding after non-urgent endoscopic treatment of esophagogastric varices.

[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

[Development and validation of an individual risk prediction tool for severe respiratory syncytial virus infection among children under five years in China].

Objective: To construct a predictive model to assess the risk of severe respiratory syncytial virus infection among children under five years in China, conduct preliminary validation of this model by using external data, and develop an individual risk assessment tool available for their parents. Methods: The admission after RSV infection was used as a marker of severe infection. Based on the evidence of RSV hospitalization-related risk factors and real-world data, such as the prevalence of various risk factors in children under five years old in China, a Monte Carlo-based individual RSV hospitalization risk prediction model for children under five years old was constructed. Taking Suzhou City as an example, the model was externally validated, and an interactive risk prediction tool (RSV HeaRT) was developed on the WeChat mini-program platform. Results: The estimation model showed that in children under five years old in China if the population did not have any risk factors for severe RSV infection, the RSV annual hospitalization rate was 2.2/1 000 (95%CI: 0.9/1 000-7.5/1 000). Based on this baseline hospitalization rate and the prevalence of related risk factors in Suzhou, the model predicted an RSV hospitalization rate of 8.0/1 000 (95%CI: 4.6/1 000-24.4/1 000) for children under five years old annually in Suzhou, which was close to the reported RSV hospitalization rate in literature (10/1 000-20/1 000). In the developed RSV HeaRT WeChat mini-program, target users (such as parents of children) could input basic information, disease history, and social environmental factors of the child into the mini-program, and the tool could provide real-time feedback on the following predicted results: First, the relative risk of hospitalization due to RSV infection in current children compared to general children; Second, the probability of hospitalization due to RSV infection within the next year; Third, the relative risk of adverse outcomes during hospitalization in the event of RSV infection. Conclusion: This study is based on real-world evidence related to RSV hospitalization risk and constructs an RSV hospitalization risk prediction model suitable for Chinese children based on the combination of the current prevalence of risk factors in children under five years old in China. The accuracy of the prediction model results has been preliminarily demonstrated. Based on this design, the RSV HeaRT developed can facilitate parents to evaluate the hospitalization risk of children.

[Current status of surveillance systems for human respiratory syncytial virus].

To conduct timely surveillance of the seasonal characteristics and disease burden of Human Respiratory Syncytial Virus (HRSV) in various geographical regions of China, and further develop more precise and effective prevention and intervention strategies, there is an urgent need for China to establish a nationwide, effective, and stable HRSV surveillance system. Through combining the current status of domestic and international HRSV surveillance systems and the existing surveillance framework in China, this study proposed an HRSV surveillance type applicable to China based on different surveillance purposes, and considering the feasibility of implementation. This article aimed to provide solid scientific and technical support to monitor the dynamic changes of HRSV epidemic timely, carry out a risk assessment and early warning, and further understand the disease burden of HRSV in China. It also helps to improve the diagnosis, prevention, and control of the HRSV diseases research and development, use, and evaluation of HRSV vaccines and drugs in China.

[Effects of canagliflozin on amino acid metabolism in atherosclerotic mice].

Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

[Canagliflozin can improve cardiac function in HFpEF rats partly by regulating ferroptosis].

Objective: To explore the effects of canagliflozin on cardiac function and its regulation of ferroptosis in rats with heart failure with preserved ejection fraction (HFpEF). Methods: Thirty-two 7-week-old Dahl salt-sensitive rats were selected and randomly divided into four groups: the control group (fed with low-salt diet), the HFpEF group (fed with high-salt diet), the canagliflozin 20 group (fed with high-salt diet and 20 mg·kg-1·d-1 canagliflozin), and the canagliflozin 30 group (fed with high-salt diet and 30 mg·kg-1·day-1 canagliflozin). Body weight and blood pressure of the rats in each group were monitored. Metabolic cage tests were conducted at the10th week of the experiment, and echocardiography was performed at the 12th week, after which the rats were killed. Blood and left ventricular samples were collected. HE staining, Masson staining, Prussian blue iron staining, and reactive oxygen species staining were performed to observe the cardiomyocyte size and shape, degree of interstitial fibrosis, iron staining, reactive oxygen species production under optical microscope. The ultrastructure of cardiomyocytes was observed under electron microscope. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression levels of proteins and mRNA related to ferroptosis in left ventricular myocardial tissue of rats in each group. Results: After 1 week of adaptive feeding, all rats survived. Metabolic cage results showed that compared with control group, rats in the HFpEF group, canagliflozin 20 group and canagliflozin 30 group had more food intake, water intake and urine output, and lower body weight (all P<0.05). These changes were more pronounced in canagliflozin 20 group and canagliflozin 30 group than in HFPEF group, and only the body weight at the 12th week showed a statistically significant difference between canagliflozin 20 group and canagliflozin 30 group (P<0.05). The blood pressure of 6th week and 12th week, heart weight and left ventricular corrected mass of 12th week of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while the ratio of early mitral valve peak velocity to late mitral valve peak velocity of 12th week was lower (all P<0.05). HE and Masson staining showed that compared to control group, the myocardial fibers in the left ventricular myocardial tissue of rats in HFpEF group were disordered, with larger cell diameter ((0.032±0.004) mm vs. (0.023±0.003) mm, P<0.05), irregular shape, obvious proliferation of interstitial collagen fibers, and higher collagen volume fraction (0.168±0.028 vs. 0.118±0.013, P<0.05). Compared with HFpEF group, rats in the canagliflozin 20 group and canagliflozin 30 had more orderly arranged myocardial fibers, more regular cardiomyocyte shape, smaller cell diameter, and lower collagen volume fraction (P<0.05). It was observed under electron microscopy that, compared to control group, most of the striated muscles in myocardial tissue of HFpEF group were broken, and the Z line and M line could not be clearly distinguished, some changes such as mitochondrial swelling, membrane thickening, cristae reduction or even disappearance occurred. In the canagliflozin 20 group and canagliflozin 30 group, the arrangement of striated muscles in the myocardial tissue of rats tended to be more regular, and the morphological changes of mitochondria were milder. Prussian blue iron staining results showed that the iron content in myocardial tissue of rats in HFpEF group was higher than that in control group, canagliflozin 20 group and canagliflozin 30 group. Reactive oxygen species staining results showed that the reactive oxygen species content in the myocardial tissue of rats in HFpEF group was higher than that of control group, canagliflozin 20 group and canagliflozin 30 group. Biochemical analysis of myocardial tissue showed that Fe2+ and malondialdehyde content in myocardial tissue of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while glutathione content was lower (all P<0.05). Western blot and RT-qPCR detection results showed that compared to control group, rats in HFpEF group had higher expression levels of transferrin receptor 1 (protein relative expression level: 1.37±0.16 vs. 0.31±0.12), acyl-CoA synthetase long-chain family member 4 (protein relative expression level: 1.31±0.15 vs. 0.63±0.09) protein and mRNA, and lower expression levels of ferritin heavy chain 1 (protein relative expression level: 0.45±0.08 vs. 1.41±0.15) protein and mRNA (all P<0.05). There was no statistically significant difference in these indicators between canagliflozin 20 group and the canagliflozin 30 group (all P>0.05). There was no significant difference in levels of glutathione peroxidase 4 protein and mRNA expression in myocardial tissue of rats in four groups(P>0.05). Conclusion: Canagliflozin improves cardiac function in HFpEF rats by regulating the ferroptosis mechanism.

First-principles property assessment of hybrid formate perovskites.

Hybrid organic-inorganic formate perovskites, AB(HCOO)3, are a large family of compounds that exhibit a variety of phase transitions and diverse properties, such as (anti)ferroelectricity, ferroelasticity, (anti)ferromagnetism, and multiferroism. While many properties of these materials have already been characterized, we are not aware of any study that focuses on the comprehensive property assessment of a large number of formate perovskites. A comparison of the properties of materials within the family is challenging due to systematic errors attributed to different techniques or the lack of data. For example, complete piezoelectric, dielectric, and elastic tensors are not available. In this work, we utilize first-principles density functional theory based simulations to overcome these challenges and to report structural, mechanical, dielectric, piezoelectric, and ferroelectric properties of 29 formate perovskites. We find that these materials exhibit elastic stiffness in the range 0.5-127.0 GPa; highly anisotropic linear compressibility, including zero and even negative values; dielectric constants in the range 0.1-102.1; highly anisotropic piezoelectric response with the longitudinal values in the range 1.18-21.12 pC/N; and spontaneous polarizations in the range 0.2-7.8 µC/cm2. Furthermore, we propose and computationally characterize a few formate perovskites that have not been reported yet.

The association of new-onset diabetes with subsequent diagnosis of pancreatic cancer-novel use of a large administrative database.

BACKGROUND: Screening options for pancreatic ductal adenocarcinoma (PDAC) are limited. New-onset type 2 diabetes (NoD) is associated with subsequent diagnosis of PDAC in observational studies and may afford an opportunity for PDAC screening. We evaluated this association using a large administrative database. METHODS: Patients were identified using claims data from the OptumLabs® Data Warehouse. Adult patients with NoD diagnosis were matched 1:3 with patients without NoD using age, sex and chronic obstructive pulmonary disease (COPD) status. The event of PDAC diagnosis was compared between cohorts using the Kaplan-Meier method. Factors associated with PDAC diagnosis were evaluated with Cox's proportional hazards modeling. RESULTS: We identified 640 421 patients with NoD and included 1 921 263 controls. At 3 years, significantly more PDAC events were identified in the NoD group vs control group (579 vs 505; P < 0.001). When controlling for patient factors, NoD was significantly associated with elevated risk of PDAC (HR 3.474, 95% CI 3.082-3.920, P < 0.001). Other factors significantly associated with PDAC diagnosis were increasing age, increasing age among Black patients, and COPD diagnosis (P ≤ 0.05). CONCLUSIONS: NoD was independently associated with subsequent diagnosis of PDAC within 3 years. Future studies should evaluate the feasibility and benefit of PDAC screening in patients with NoD.

Genome Sequence Resource of Fusarium proliferatum f. sp. malus domestica MR5, the Causative Agent of Apple Replant Disease.

Apple replant disease (ARD) caused by the fungal pathogen Fusarium proliferatum f. sp. malus domestica (Fpmd) MR5 brings annual losses to apple production within China. However, the genomic information of the pathogen is not yet available. Here, we obtained the whole-genome sequence of the highly virulent Fpmd MR5 using the Illumina PE150 platform. The genome size was 42.76 Mb and consisted of 9,047 genes. The GC content was 48.80%, and several genes potentially associated with pathogenicity were identified, such as carbohydrate-active enzymes, secreted proteins, and secondary metabolite gene clusters. There were 260 specific virulence factor genes, mainly related to fungal vegetative growth and the production of cell wall-degrading enzymes. These data will aid future studies investigating host-pathogen interactions and help us develop suitable disease management strategies.

Transcriptome analysis and identification of genes associated with individual fertilisation rate differences in hen infundibulum.

1. Fertilisation rate is closely related to the reproductive performance and economic status of chicken laying breeders. In this study, two flocks (n = 1,029 in population I and n = 358 in population II) in the later laying period were used for investigating the individual differences among population fertilisation rates (FRs).2. The funnel and distal parts of the infundibulum were collected from nine individuals (five with low FR and four with high FR from population II) and RNA-sequencing (RNA-seq) method was used to investigate the transcriptome differences in fertilisation. Differences in fertilisation regulation were investigated by comparing the different parts (funnel and distal) of the infundibulum between the low FR and high FR groups.3. There were notable individual FR differences in both categories. Some individuals had a relative high FR (≥90%) for a long time (>5 days after AI), contrarily, some individuals lost the ability to fertilise eggs in a very short time.4. Differentially expressed genes (DEGs), such as DUSP7, PPP1R3B, FYB, OVA, OVALX and OVALY may be associated with sperm functional regulation, fertilisation and early-stage fertilised ovum development processes. DEGs such as AVBD1, AVBD2, AVBD6, NFATC2 and BANK1 indicated a severe immune response to sperm survival and fertilisation in the oviduct.5. The results suggested that individual differences should be considered in the breeding and reproduction process. The DEGs identified in this study may promote our understanding of different fertilisation regulation in laying breeders.

Effects of betaine supplementation on reproductive performance of breeding geese.

1. An experiment feeding three concentrations of betaine was conducted using breeding geese to analyse the reproductive performance, serum biochemical indexes, egg quality and intestinal immunity.2. A total of 450 female and 90 male Jiangnan White breeding geese were divided into three treatments, with five pen replicates each containing 30 female geese and 6 male geese.3. The results showed that there was no significant effect on the reproductive performance, serum biochemical indexes or jejunal villi goblet cells of geese with different levels of betaine in the diet (P > 0.05). Compared with the control group, the addition of 2.5 g/kg betaine to the diet showed a tendency to increase egg mass (P > 0.05) the betaine content in the yolk (P < 0.05). Feeding betaine significantly increased the height of jejunal villi and egg yolk total cholesterol content in female geese (P < 0.05).4. In conclusion, adding betaine to the goose diet was effective in its ability to improve intestinal structures. Adding 2.5 g/kg betaine to feed significantly increased the content of TCHOL and betaine in goose eggs.

Effects of testis testosterone deficiency on gene expression in the adrenal gland and skeletal muscle of ducks.

1. Testosterone has an anabolic effect on skeletal muscle. The testes produce most of the testosterone in vivo, while the adrenal glands contribute smaller amounts. When testis testosterone is deficient the adrenal gland increases steroid hormone synthesis, which is referred to as compensatory testicular adaptation (CTA).2. To reveal the effects of testis testosterone deficiency on adrenal steroid hormones synthesis and skeletal muscle development, gene expression related to adrenal steroid hormones synthesis and skeletal muscle development were determined by RNA-seq.3. The results showed that castrating male ducks had significant effects on their body weight but no significant impact on cross-sectional area (CSA) or density of pectoral muscle fibres. In skeletal muscle protein metabolism, expression levels of the catabolic gene atrogin1/MAFbx and the anabolic gene eEF2 were significantly higher, with concomitant increases after castration. The adrenal glands' alteration of the steroid hormone 11ß-hydroxylase (CYP11B1) was significantly lower following castration.4. Expression pattern analysis showed that the adrenal glands' glucocorticoid receptor (NR3C1/GR) had a potential regulatory relationship with the skeletal muscle-related genes (Pax7, mTOR, FBXO32, FOXO3, and FOXO4).5. The data showed that castration affected muscle protein metabolism, adrenal steroid and testosterone synthesis. In addition, it was speculated that, after castration, steroid hormones produced by the adrenal gland could have a compensatory effect, which might mediate the changes in skeletal muscle protein metabolism and development.

[Nomogram prediction model of cervical anastomotic leakage after esophageal cancer surgery].

Objective: To retrospectively analyze the risk factors of anastomotic leakage in the neck after esophageal cancer and establish a nomogram prediction model that can accurately predict the occurrence of anastomotic leakage in the neck of the patient. Methods: The study retrospectively analyzed 702 patients who underwent radical esophageal cancer surgery between January 2010 and May 2015 at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. A multivariate logistic regression model was used to determine the risk factors for neck anastomotic leak, and a nomogram model was constructed, internal validation methods were used to evaluate and verify the predictive effectiveness of the nomogram. Results: There were 702 patients in the whole group, 492 in the training group and 210 in the validation group. The incidence of postoperative cervical anastomotic leak was 16.1% (79/492) in 492 patients with esophageal cancer in the training group. Multifactorial analysis revealed calcification of the descending aorta (OR=2.12, 95% CI: 1.14, 3.94, P=0.018), calcification of the celiac artery (OR=2.29, 95% CI: 1.13, 4.64, P=0.022), peripheral vascular disease (OR=5.50, 95% CI: 1.64, 18.40, P=0.006), postoperative ventilator-assisted breathing (OR=5.33, 95% CI: 1.83, 15.56, P=0.002), pleural effusion or septic chest (OR=3.08, 95% CI: 1.11, 8.55, P=0.031), incisional fat liquefaction and infection (OR=3.49, 95% CI: 1.68, 7.27, P=0.001) were independent risk factors for the development of cervical anastomotic leak after esophageal cancer surgery. The results of the nomogram prediction model showed that the consistency indices of the training and external validation groups were 0.73 and 0.74, respectively (P<0.001), suggesting that the prediction model has good predictive efficacy. Conclusion: The nomogram prediction model can intuitively predict the incidence of postoperative cervical anastomotic leakage in patients with high prediction accuracy, which can help provide a clinical basis for preventing cervical anastomotic leak and individualized treatment of patients.

Is the 'safe zone' identified in preoperative computed tomography helpful for choosing optimal implant for fixation of radial head fracture?

The purpose of this study is to assess the clinical significance of the radiologic safe zone based on computed tomography and to compare the outcomes of three different implants for fixation of isolated radial head fractures. We retrospectively reviewed 367 patients who underwent internal fixation for isolated radial head fractures. We newly defined two subtypes of Mason type II fractures associated with the radiographic safe zone (IIA, two-part fracture allowing for safe fixation of plate; IIB, two-part fracture not allowing for safe fixation). 170 patients (CCS group, n = 82; HCS group, n = 31; plate group, n = 57) were investigated with no significant differences in demographics. The range of pronation and supination at 1 month postoperatively (P = 0.04 and P = 0.04) and the range of supination at 6 and 12 months postoperatively (P = 0.03 and P = 0.03) were significantly smaller in the plate group. In Mason type IIB fractures, the average MEPS was higher in the CCS and HSC groups than in the plate group (P = 0.01 and P = 0.02). And the average DASH score was lower in the CCS and HCS groups (P < 0.01 and P < 0.01). Evaluation of the radiologic safe zone is potentially helpful in selecting better surgical fixation option. For type III fractures, 2.3-mm cortical screws would be a better option than Acutrak screws. Plates would not be suitable for type IIB radial head fractures.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain mediators including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores of the study group and the control group before treatment were 7.94±0.76 and 8.20±0.81, and PSQI scores were 16.84±3.90 and 16.29±3.84, respectively, with no statistically significant differences (both P>0.05). After 4 weeks of treatment, the VAS scores of the two groups were 2.84±0.80 and 3.35±0.87, and PSQI scores were 6.78±1.90 and 7.98±2.40, respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). There were no significant differences of the serum levels of NPY, PGE2, SP and ß-endorphin before treatment in the study group and control group (all P>0.05). After 4 weeks of treatment, the levels of NPY, PGE2, SP and ß-Endorphin in the study group were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group, respectively. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain intensity and sleep quality of patients with severe thoracic PHN and reduce the levels of pain mediators, with a high safety profile.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain factors including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-Endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores and PSQI scores of the study group and the control group before treatment were (7.94±0.76), (8.20±0.81), (16.84±3.90) and (16.29±3.84), respectively, with no statistically significant difference (both P>0.05). After 4 weeks of treatment, the VAS scores and PSQI scores of the two groups were (2.84±0.80), (3.35±0.87), (6.78±1.90) and (7.98±2.40), respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). Serum levels of NPY, PGE2, SP and ß-Endorphin were (298.5±31.0) ng/L, (92.3±11.0) µg/L, (156.8±21.4) ng/L, and (8.6±1.6) ng/L in the study group and (304.2±28.6) ng/L, (94.4±12.9) µg/L, (152.7±23.8) ng/L and (8.2±1.8) ng/L in the control group, with no significant differences (all P>0.05). After 4 weeks of treatment, levels of NPY, PGE2, SP and ß-Endorphin were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain and sleep quality of patients with severe thoracic PHN and reduce the level of pain factors, with a high safety profile.

[Efficacy and safety of pulsed radiofrequency combined with gabapentin in the treatment of acute herpetic neuralgia].

Objective: To explore the clinical efficacy and safety of pulsed radiofrequency (PRF) combined with gabapentin in the treatment of acute herpetic neuralgia (AHN). Methods: A total of 123 AHN patients were retrospectively selected in Henan Provincial People's Hospital from November 2019 to July 2022, who were divided into two groups based on treatment methods: control group (treated with gabapentin, n=61) and study group (treated with gabapentin and PRF, n=62). The visual analog scale (VAS) was utilized for pain severity assessment and the self-rating scale for sleep (SRSS) was utilized for sleep quality evaluation. The differences in serum levels of interleukin (IL)-10, chemokine ligand 10 (CXCL-10), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), IL-2 and IL-6 before and after treatment were compared between the two groups. The overall treatment effectiveness and the occurrence rates of postherpetic neuralgia and adverse reactions were evaluated in both groups. Results: Among the study group patients, 28 were male and 34 were female, and the age was (62.8±8.5) years. Among the control group patients, 35 were male and 26 were female, and the age was (64.0±7.8) years. The VAS scores of the study group before and after treatment were 7.96±1.33 and 1.52±0.60, respectively, while the control group were 7.68±1.52 and 2.70±0.64. The SRSS scores before and after treatment in the study group were 31.74±5.90 and 12.06±2.81, respectively, while those in the control group were 33.10±5.54 and 14.14±2.96, respectively. Before treatment, there were no statistically differences of the VAS scores and SRSS scores in both groups (all P>0.05). After treatment, the VAS scores and SRSS scores in both groups decreased compared with before treatment (all P<0.05), the study group's VAS scores and SRSS scores were lower than those in the control group (all P<0.05). Before treatment, there were no statistically differences of the serum levels of IL-10, CXCL-10, PGE2, COX-2, IL-2 and IL-6 in both groups (all P>0.05). After treatment, the serum levels of IL-10, CXCL-10, PGE2, COX-2 and IL-6 in both groups decreased compared with before treatment, while the IL-2 level increased. Additionally, the study group had lower serum levels of IL-10, PGE2, COX-2 and IL-6 compared with the control group (all P<0.05). After treatment, the study group had 35 cases of cure, 26 cases of effectiveness, and 1 case of ineffectiveness, while the control group had 22 cases of cure, 31 cases of effectiveness, and 8 cases of ineffectiveness. The overall treatment efficacy of the study group was better than that of the control group (P=0.012). The incidence of postherpetic neuralgia in the study group after treatment was 16.1% (10/62), which was lower than that in the control group, which was 37.7% (23/61) (P<0.05). There were no statistically differences of the occurrence rates of adverse reactions in both groups (all P>0.05). Conclusion: Combining PRF with gabapentin for the treatment of AHN demonstrates better overall efficacy and safety, which can more effectively alleviate pain, improve sleep, and reduce inflammatory cytokine levels.

[Survey of Helicobacter pylori levofloxacin and clarithromycin resistance rates and drug resistance genes in Ningxia, 2020-2022].

Objective: To explore the rate of Helicobacter pylori (Hp) resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia, and to assess the concordance between phenotypic resistance and genotypic resistance. Methods: Cross-sectional study. Patients diagnosed with Hp infection in 14 hospitals in Ningxia region from February 2020 to May 2022 were retrospectively selected. Hp strains were isolated from gastric biopsy specimens of Hp-infected patients and subjected to phenotypic drug sensitivity testing and detection of resistance genes to analyze the rate of Hp resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia region; and the concordance rate and Kappa concordance test were used to assess the concordance between phenotypic resistance and genotypic resistance. Results: A total of 1 942 Hp strains were isolated and cultured, and among the infections, 1 069 cases (55.0%) were male and 873 cases (45.0%) were female, aged (50.0±12.5) years (15-86 years). The rates of Hp resistance to levofloxacin and clarithromycin in Ningxia were 42.1% (818/1 942) and 40.1% (779/1 942), respectively, and the rate of dual resistance to both was 22.8% (443/1 942). The rate of resistance to levofloxacin and clarithromycin of Hp strains from female patients was higher than in male patients (levofloxacin: 50.4%(440/873) vs 35.4%(378/1 069); clarithromycin: 44.4%(388/873) vs 36.6%(391/1 069), both P<0.001). Among the GyrA gene mutations associated with levofloxacin resistance, the differences in mutation rate of amino acid at positions 87 and 91 were statistically significant in both drug-resistant and sensitive strains(both P<0.001), except for Asn87Thr. Hp strains were statistically significant for levofloxacin (Kappa=0.834, P<0.001) and clarithromycin (Kappa=0.829, P<0.001) had good concordance in resistance at the phenotypic and genotypic levels. Conclusion: The resistance of Hp to levofloxacin and clarithromycin in Ningxia region is severe, and there is good consistency between genotypic and phenotypic resistance.