Photo-induced structural dynamics of o-nitrophenol by ultrafast electron diffraction.

The photo-induced dynamics of o-nitrophenol, particularly its photolysis, has garnered significant scientific interest as a potential source of nitrous acid in the atmosphere. Although the photolysis products and preceding photo-induced electronic structure dynamics have been investigated extensively, the nuclear dynamics accompanying the non-radiative relaxation of o-nitrophenol on the ultrafast timescale, which include an intramolecular proton transfer step, have not been experimentally resolved. Herein, we present a direct observation of the ultrafast nuclear motions mediating photo-relaxation using ultrafast electron diffraction. This work spatiotemporally resolves the loss of planarity which enables access to a conical intersection between the first excited state and the ground state after the proton transfer step, on the femtosecond timescale and with sub-Angstrom resolution. Our observations, supported by ab initio multiple spawning simulations, provide new insights into the proton transfer mediated relaxation mechanism in o-nitrophenol.

[Marked improvement in rheumatoid lung nodules after treatment with tocilizumab combined with glucocorticoids and leflunomide: a case report and literature review].

Rheumatoid arthritis (RA), a chronic autoimmune disorder, is characterized by erosive inflammation of bone and cartilage, leading to progressive joint destruction. Pulmonary involvement occurs in approximately 60% of RA patients, manifests most commonly as interstitial lung disease and, less commonly, as rheumatoid lung nodules. Here, we report a 50-year-old woman, non-smoker, with recurrent cough and sputum of 7 years' duration, accompanied by a chest CT showing multiple cavitary nodules in both lungs. She had been treated empirically at several medical centers and was finally diagnosed with rheumatoid lung nodules. Marked improvement in rheumatoid lung nodules was observed after treatment with tocilizumab in combination with glucocorticoids and leflunomide. The aim of this study was to improve clinicians' understanding of rheumatoid lung nodules by analyzing the clinical features, diagnosis, and treatment of this case, and reviewing the relevant medical literature.

[A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer].

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

[A new understanding of wound repair after surgery for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. Transurethral resection of prostate (TURP), as an important BPH treatment, is also the most effective way to relieve prostatic obstruction. However, postoperative complications, such as lower urinary tract symptoms (LUTS), infection, hematuria and bladder neck contracture, may still occur, which seriously impact the therapeutic effect and patients' quality of life. The wound healing after BPH surgery is closely associated with the occurrence of postoperative complications. Therefore, comprehensively understanding the influencing factors of wound healing and designing tailored interventions will be particularly important for reducing postoperative complications of BPH.

[Expert consensus on endocrine therapy of breast cancer (2023 edition)].

Endocrine therapy is the primary systemic therapy for hormone receptor-positive breast cancer, which runs through the whole process of treatment for early and metastatic breast cancer. The development of new endocrine agents and targeted drugs such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors has improved outcome of patients with hormone receptor-positive breast cancer and changed the treatment landscape. The update of clinical research data provides more treatment options, calling for treatment optimization. Experts had a deep discussion around the hot topics on endocrine therapy of breast cancer, and formulated the'Expert consensus on endocrine therapy of breast cancer (2023 edition)'.This consensus is based on research data worldwide and clinical practice experience, with the aims of standardizing clinical diagnosis and optimizing treatment in neoadjuvant, adjuvant and metastatic setting of hormone receptor-positive breast cancer.

[Investigate the role of neutrophil extracellular traps in immune checkpoint inhibitor-associated myocarditis with programmed death protein-1 inhibitors involvement].

Objective: To investigate the role of neutrophil extracellular traps (NETs) in immune checkpoint inhibitor-associated myocarditis (ICIAM) with programmed death protein-1 (PD-1) inhibitors involvement, and to explore the therapeutic potential of targeting NETs in the treatment of ICIAM. Methods: Thirty 6-week-old male BALB/c mice were randomly divided into control group (n=10), myocarditis group (n=10), and treatment group (n=10). Apart from the control group, each mouse was subcutaneously injected with 100 µl of complete Freund's adjuvant containing 250 µg of mouse cardiac troponin I peptide on the 1st and 7th day. Starting on the 8th day, PD-1 inhibitor (15 µg/per mouse) was intraperitoneally injected every other day for a total of 5 times. Since 1 day before the beginning of PD-1+TnI injection, the treatment group was injected with PF-1355 (50 mg·kg-1·d-1) for 16 consecutive days. The mice's general state was observed during the whole process. Real-time fluorescence quantitative PCR (RTFQ-PCR) was carried out to evaluate the transcriptional regulation of neutrophil related chemokines, NETs, pyronecrosis related factors and proinflammatory cytokines. Immunohistochemistry, immunofluorescence and western blot were applied to determine the changes of pyrosis related molecules. Echocardiography showed the differences of main cardiac indexes while cardiac pathology compared the degree of inflammatory infiltration in 3 gruops. Results: The immunofluorescence intensity of myocardial NETs in the myocarditis group was significantly increased compared to the control group mice (2.49±0.08 and 0.99±0.26, P<0.001). The protein expression levels of pyroptosis-related NLRP3, cleaved-Caspase 1, Caspase 1, cleaved-GSDMD, GSDMD, IL-1ß and IL-18 in myocardial tissue of the model group were higher than those of the control group (all P<0.05). After treatment with PF-1355, compared to the myocarditis group, the left ventricular ejection fraction (LVEF) (73.58%±5.31% and 58.12%±3.19%, P<0.001) and left ventricular fraction shortening (LVFS) (39.78%±4.31% and 33.89%±2.19%, P<0.001) increased. H-E staining showed a reduction in inflammatory infiltration area in the treatment group compared to the myocarditis group (30.12%±3.57% and 14.92%±2.46%, P<0.001). The immunofluorescence intensity of NETs decreased in the treatment group compared to the myocarditis group (2.52±0.04 and 1.03±0.05, P<0.001). The levels of NLRP3 and other pyroptosis-related molecules were downregulated in the treatment group compared to the myocarditis group (all P<0.05). Conclusions: NETs lead to myocardial cell pyroptosis by activating the NLRP3 inflammasome in PD-1 inhibitor-associated myocarditis. The specific MPO inhibitor PF-1355 shows a therapeutic potential by regulating the formation of NETs, decreasing NLRP3 level and relieving myocardial pyroptosis, thus reducing myocardial damage.

[Primary adrenal NK/T cell lymphoma: a clinicopathologic analysis of six cases].

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.

[Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome].

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

Anisotropic spin-orbit torque generation in epitaxial SrIrO3 by symmetry design.

Spin-orbit coupling (SOC), the interaction between the electron spin and the orbital angular momentum, can unlock rich phenomena at interfaces, in particular interconverting spin and charge currents. Conventional heavy metals have been extensively explored due to their strong SOC of conduction electrons. However, spin-orbit effects in classes of materials such as epitaxial 5d-electron transition-metal complex oxides, which also host strong SOC, remain largely unreported. In addition to strong SOC, these complex oxides can also provide the additional tuning knob of epitaxy to control the electronic structure and the engineering of spin-to-charge conversion by crystalline symmetry. Here, we demonstrate room-temperature generation of spin-orbit torque on a ferromagnet with extremely high efficiency via the spin-Hall effect in epitaxial metastable perovskite SrIrO3 We first predict a large intrinsic spin-Hall conductivity in orthorhombic bulk SrIrO3 arising from the Berry curvature in the electronic band structure. By manipulating the intricate interplay between SOC and crystalline symmetry, we control the spin-Hall torque ratio by engineering the tilt of the corner-sharing oxygen octahedra in perovskite SrIrO3 through epitaxial strain. This allows the presence of an anisotropic spin-Hall effect due to a characteristic structural anisotropy in SrIrO3 with orthorhombic symmetry. Our experimental findings demonstrate the heteroepitaxial symmetry design approach to engineer spin-orbit effects. We therefore anticipate that these epitaxial 5d transition-metal oxide thin films can be an ideal building block for low-power spintronics.

[The clinical efficacy of the stratification medical treatment based on the risk estimation of motor complications in Parkinson's disease].

Objectives: To evaluate the clinical efficacy of the stratification medical treatment based on the motor complications risk estimation in improving the quality of life, motor symptoms and delaying the motor complications in Parkinson's patients. Methods: Outpatients and inpatients from Xinhua Hospital, Shanghai Jiao Tong University, were recruited between November 2019 and June 2020. The participants were all clinically diagnosed with PD and treated with anti-PD medications, but had no history of motor complications, with the 8-item Parkinson's disease questionnaire summary index (PDQ-8 SI)>18.59. At baseline, the demographic characteristics, PD medical history, levodopa dosage (LD) and levodopa equivalent dosage (LED) were collected, and the evaluation of PDQ-8, Unified Parkinson's disease rating scale (UPDRS)-Ⅱ and Ⅲ, Hoehn and Yahr (H&Y) grade, Hamilton anxiety scale-14 (HAMA-14), Hamilton depression scale-24 (HAMD-24), mini-mental state examination (MMSE), Pittsburgh sleep quality index (PSQI), and Epworth sleepiness scale (ESS) tools was accomplished in all participants. Meanwhile, a Parkinson's disease risk estimation scale for motor complications was used to assess patients' risk of motor complications, and thus the medication was stratified in PD patients accordingly. During the 6-month and 12-month follow-ups, the evaluation of the above-mentioned parameters was repeated in all participants. At the 3-month and 9-month follow-ups, the information of anti-PD medications, the occurrence of motor complications (motor fluctuations and dyskinesia) and adverse drug reactions were recorded, and PDQ-8 was also evaluated. Results: Two hundred and fifty-one patients completed the 1-year follow-up, with 135 males and 116 females. At baseline, the median age of the patients was 66 (60, 71) years and the median PDQ-8 SI was 31.2 (21.9, 40.6). Additionally, 15.9% (40/251) of the patients were at high risk of motor fluctuation, and 7.2% (18/251) were at high risk of dyskinesia. There were significant differences in the age of onset, disease duration, PD treatment duration, the scores of UPDRS-Ⅱ and Ⅲ, H&Y Grade, and PDQ-8 SI among PD patients of different risk groups (all P<0.05). In the 12th month, the median of PDQ-8 SI, Δ PDQ-8 SI and Δ UPDRS-Ⅲ was 12.5 (9.4, 18.8), -15.6 (-21.9, -9.4) and -9(-16, -4), respectively, which was statistically different from that of baseline (all P<0.05). The change of UPDRS-Ⅱ scores in the group with high risk of motor fluctuation was statistically different from that in the groups with low and moderate risk (P<0.05). The changes of PSQI score, LD and LED in the group with high risk of dyskinesia was statistically different from those in the groups with low and moderate risk (all P<0.05). During the follow-up, the incidence of motor fluctuation and dyskinesia was 9.56% (24/251) and 5.97% (15/251), respectively. Conclusion: The stratification medical treatment might have a positive intervention effect on promoting a better quality of life, improving motor symptoms and delaying motor complications in PD patients.

[Association of glutamate receptor metabotropic 5 polymorphisms with schizophrenia susceptibility in a Chinese Han population].

Objectives: To investigate the association of single nucleotide polymorphisms (SNP) of glutamate receptor metabotropic 5 (GRM5) gene with schizophrenia susceptibility(SZ) in a Chinese Han population. Methods: Twenty-two SNPs located in GRM5 gene in 528 paranoid SZ patients and 528 control subjects recruited from northern Henanwere analyzed. The clinical features of 267 first-episode SZ patients were assessed with the Positive and Negative Syndrome Scale (PANSS). Results: The SZ group included 264 males and 264 females, aged (27±8) years; the healthy control group had 264 males and 264 females, aged (28±8) years.The differences in the genotypic and allelic frequencies of two SNPs (rs567990 and rs12421343) were statistically significant between the SZ patients and control groups (all P<0.05). The allele frequency of rs504183 was also statistically different between the two groups (P=0.030). When the subjects were stratified by sex, the genotypic and allelic frequencies of rs12421343 in female subjects were statistically different between the SZ patients and control groups. The allele frequencies of SNPs (rs12422021, rs567990, and rs7101540) were also statisticallydifferent between the two groups (all P<0.05). Meanwhile, rs567990 AG+GG carriers had a higher risk for SZ than AA carriers in female subjects(OR=1.946, 95%CI: 1.264-2.995). In addition, the patients with different genotypes (GG, AA+AG) of rs12422021 showed statistically significant differences in PANSS total score(84.8±24.4 vs 75.3±18.6), positive (16.2±4.3 vs 14.4±4.2), excitement (12.4±5.1 vs 10.2±4.1) and cognitive impairment factor scores (15.2±6.8 vs 13.3±3.9) (all P<0.05). The patients with AC and the other two genotypes (AA and CC) of rs504183 showed statistically significant differences in PANSS negative factor score(27.4±9.9 vs 24.7±8.4 and 23.4±8.1, both P<0.05). Conclusion: The current study provides further evidence that GRM5 is associated with SZ, and suggests a putative sex difference.

[Combined application of field epidemiology and laboratory etiology analysis in the investigation of a foodborne disease outbreak in Xinjiang uygur Autonomous Region, 2016].

Objectives: To analyze the causes of a foodborne outbreak in rural areas of Xinjiang between April 2 and April 5 in 2016. Methods: Cases and the relevant background information were obtained by consulting outpatient records of local health centers and regional people's hospitals and interviewing doctors and residents. All samples were collected by the laboratory test through epidemiological and food hygiene investigations. The χ2 test (Fisher's exact probability method) was used to compare differences in incidence rates. Molecular typing, virulence genes and single nucleotide polymorphisms (SNPS) were analyzed by using Pulsed Field Gel Electrophoresis (PFGE) and Whole Genome Sequencing (WGS). Results: A total of 142 cases were found in this study, with incidence rate at 5.7‰ (142/24 979). Among all cases, the main symptoms were nausea (94%), vomiting (92%) and abdominal pain (67%), and the incubation period was about 2 h (1-7.5 h). There were 16 Staphylococcus aureus isolates identified and all of them could produce A+C+E mixed enterotoxin. PFGE showed 100% homology. WGS further revealed that there were 9 and 1 strains contained by Sequence Type 1 (ST1) and ST5405, respectively. All ST1 strains were in the same clade on the genome tree. Among these, 7 strains shared close proximity (74 SNPs) and 2 strains shared close relationships as well (127 SNPs). The S. aureus isolates that caused the outbreak were introduced by a mutant isolate from the milk supply station. Conclusions: This foodborne outbreak was mainly caused by Staphylococcus aureus contamination.

[Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins].

Objective: To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation. Methods: Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD. Results: A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95%CI: 0.49-0.55) and 0.76 (95%CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD (rA=0.10, 95%CI:0.02-0.17). Conclusion: In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

[Phacoemulsification combined with goniosynechialysis under a gonioscope in the treatment of angle-closure glaucoma: the effect of reopening the synechial anterior chamber angle].

A total of 170 consecutive patients (181 eyes) who were diagnosed with primary angle-closure glaucoma (PACG) and underwent phacoemulsification and intraocular lens implantation (PEI) combined with goniosynechialysis (GSL) with an instrument under a gonioscope in the Eye Hospital, Wenzhou Medical University from January 1, 2017 to December 31, 2019 were observed. Anterior chamber angle synechiae of 0 (0, 2) clock hour were released after PEI, while after combined goniosynechialysis, synechiae of 6 (3, 8) clock hours were further released. No matter in chronic PACG and acute PACG with cornea edema, the extent of anterior chamber angle synechiae was different before surgery and after PEI, and so was it in post-PEI and PEI-GSL prospectively (all P<0.01). Phacoemulsification alone can reopen the synechial anterior chamber angle in both chronic PACG and acute PACG in part, but not sufficiently. Combined goniosynechialysis under a gonioscope with an instrument is essential and effective.

Sessile serrated adenoma of the appendix coexists with anaplastic carcinoma mural nodules originating from ovarian mucinous tumors: A case report.

Sessile serrated adenomas (SSA) of the appendix and anaplastic carcinoma mural nodules arising in the mucinous ovarian tumors (MOT) are rare lesions. We report a case of SSA in the appendix coexisting with an anaplastic carcinoma mural nodule in MOT. No BRAC1/BRAC2 germline mutations were found in the peripheral blood sample. The paraffin-embedded tissue from normal tissue (as a control), MOT, mural nodule, and SSA of the appendix were separately sequenced by next-generation sequencing (NGS). Based on the NGS results, stop-gain, chromosome DEL or TRA in mural nodules and SSA were detected, which were different from those in the mucinous tumors. In conclusion, we reported a case of SSA in the appendix coexisting with a mural nodule in MOT. We describe the morphological characteristics and molecular detection results in this case. There was no clear genetic evidence of a correlation between these two rare pathological types.

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.

Lipopolysaccharide inhibits hypothalamic Agouti-related protein gene expression via activating mechanistic target of rapamycin signaling in chicks.

Lipopolysaccharide (LPS) induces profound anorexia in birds. However, the neuronal regulatory network underlying LPS-provoked anorexia is unclear. To determine whether any cross talk occurs among hypothalamic mechanistic target of rapamycin (mTOR) and LPS in the regulation of appetite, we performed an intracerebroventricular injection of rapamycin (an mTOR inhibitor) on LPS-treated chicks. The results indicate that peripheral administrations of LPS decreased the agouti-related protein (AgRP) mRNA level, but increased the phosphorylated mTOR and nuclear factor-кB (NF-кB) protein level. Blocking mTOR significantly attenuated LPS-induced anorexia, AgRP suppression, and p-NF-кB increase. Thus, the results suggest that LPS causes anorexia via the mTOR-AgRP signaling pathway, and mTOR signaling is also associated with the regulation of LPS in p-NF-кB.

[Construction of artificial neural network model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer].

Objective: To explore and establish an artificial neural network (ANN) model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer. Methods: A set of FOLFOX chemotherapy data from a group of patients with metastatic colorectal cancer (mCRC) (GSE104645) was downloaded from the GEO database as a training set. According to the FOLFOX protocol, the efficacy was divided into two groups: the chemo-sensitive group (including complete response and partial response) and the chemo-resistant group (including stable disease and progressive disease), including 31 cases in the sensitive group and 23 in the resistant group. Then, chip data (accessible number: GSE69657) from Fujian Medical University Union Hospital were chosen as a test set. A total of 30 patients were enrolled in the study, including 13 in the sensitive group and 17 in the resistant group. The batch effect correction was performed on the expression values of the two sets of matrices using the R 3.5.1 software Combat package. The gene expression difference of sensitive and resistant group in GSE104645 was analyzed by the GEO2R platform. P<0.05 and the absolute value of log(2)FC>0.33 (FC abbreviation of fold change) were used as the threshold value to screen the drug resistance and sensitive genes of the FOLFOX regimen. An ANN was constructed using the multi-layer perceptron (MLP) to perform the FOLFOX regimen on the GSE104645 dataset. The GSE69657 expression matrix and clinical efficacy parameters were then used for retrospective verification. Receiver operating characteristic(ROC) curves were used to evaluate the test results and predictive power. Results: A total of 2, 076 differentially expressed genes in GSE104645 were selected, of which 822 genes were up-regulated and 1, 254 genes were down-regulated in the chemo-resistance group. The down-regulated genes were sensitive genes. GO analysis of the biological processes in which the differentially expressed genes were involved, revealed that they were mainly involved in the regulation of substance metabolism. A total of 39 genes were included in the final model construction. This was a neural network model with two hidden layers. The accuracy of predicting training samples and test samples was 75.7% and 76.5%, respectively, and the area under the ROC curve was 0.875. The chip data set of our department (GSE69657) was set as the test set, and the area under the ROC curve was 0.778. Conclusions: In this study, an artificial neural network model is successfully constructed to predict the efficacy of first-line FOLFOX regimen for metastatic colorectal cancer based on the microarray, and an independent external verification is also conducted. The model has good stability and well prediction efficiency. Besides, the results of this study suggest that the gene functions related to oxaliplatin resistance are mainly enriched in the regulation process of substance metabolism.

[Risk factors and clinical prognosis analysis of carbapenem-resistant Enterobacterales bacteria nosocomial infection].

Objective: To explore the risk factors for carbapenem-resistant Enterobacterales (CRE) infection and death. Methods: A case-control analysis of 482 inpatients in 18 secondary or tertiary hospitals in Beijing in 2018 was conducted. Patients infected by CRE were selected as the case group (n=247), and infected by carbapenem susceptible Enterobacterales (CSE) as the control group (n=235). The risk factors and clinical prognosis of CRE infection were analyzed by single factor analysis and multivariate logistic regression analysis. Results: CRE were resistant to most antimicrobials, but were highly sensitive to colistin and tigecycline, with sensitivity of 94.0% and 99.5%, respectively. Multivariate analysis showed that prior 30-day tracheal intubation (OR=2.607, 95%CI: 1.655-4.108, P<0.001), empirical treatment using third or fourth generation cephalosporins (OR=2.339, 95%CI: 1.438-3.803, P=0.001), carbapenems (OR=2.468, 95%CI: 1.610-3.782, P<0.001) and quinolones (OR=2.042, 95%CI: 1.268-3.289, P=0.003) were independent risk factors for CRE infection. Mechanical ventilation (OR=3.390, 95%CI: 1.454-7.904, P=0.005), heart failure (OR=4.679, 95%CI: 1.975-11.083, P<0.001), moderate or severe liver disease (OR=3.057, 95%CI: 1.061-8.806, P=0.038), prior 30-day quinolones exposure (OR=2.882, 95%CI: 1.241-6.691, P=0.014) and septic shock (OR=7.772, 95%CI: 3.505-17.233, P<0.001) were independent risk factors for death after CRE infection. Conclusions: Reducing the use of antimicrobials and invasive procedures such as prior 30-day tracheal intubation may reduce the probability of CRE infection. Grading the severity of the underlying disease in patients with CRE infection, as well as predicting and preventing the occurrence of septic shock will help reduce the risk of death.

[Analysis of the effect of modified cervical cerclage in the treatment of cervical insufficiency].

Objective: To discuss the surgical effect of modified cervical cerclage for the treatment of pregnant women with cervical insufficiency. Methods: The clinical data of 225 pregnant women who underwent modified cervical cerclage in Qilu Hospital (Qingdao) were selected for retrospective analysis from April 2014 to June 2020. Surgical success rate, full-term birth rate, preterm birth rate, prolonged pregnancy weeks and newborn birth weight were compared between singleton and twin pregnancies, preventive cerclage and emergency cerclage, surgery before and after 18 weeks, naturally and in vitro fertilization and embryo transfer (IVF-ET) conceived pregnant women respectively. Results: Among the 225 pregnant women, the gestational weeks of surgery were 14-24+5 weeks, mean gestational weeks of delivery were 38+2 weeks (35+5-39+3 weeks), the number of prolonged gestation were (20.3±5.2) weeks, and the newborn birth weight was (3 065±735) g; the overall surgical success rate was 92.9% (209/225), and the miscarriage rate was 7.1% (16/225); among the surviving newborns, the full-term birth rate was 73.7% (154/209), and the preterm birth rate was 26.3% (55/209). All cases had no intraoperative complications. Among the 225 pregnant women, 202 (89.8%, 202/225) cases were singleton pregnancies, and 23 (10.2%, 23/225) cases were twin pregnancies; 201 (89.3%, 201/225) cases underwent preventive cervical cerclage, and 24 (10.7%, 24/225) cases underwent emergency cervical cerclage; 190 (84.4%, 190/225) cases underwent the surgery before 18 weeks, and 35 (15.6%, 35/225) cases underwent the surgery after 18 weeks; 49 (21.8%, 49/225) cases were conceived by IVF-ET. There was no statistically significant difference in the overall surgical success rate of single and twin group (P>0.05). The full-term birth rate, newborn birth weight and prolonged pregnancy weeks of single group were higher than those of twin group (P<0.05). There were no statistical differences between preventive and emergency cerclage in overall surgical success rate, full-term birth rate, preterm birth rate, and newborn birth weight (all P>0.05). The pregnancy prolonged weeks of preventive cerclage was higher than that of emergency cerclage (P<0.05). There were no statistically significant differences in the overall surgical success rate, full-term birth rate, preterm birth rate and birth weight of newborns at different surgical timings (all P>0.05). The pregnancy prolonged week for those who underwent surgery before 18 weeks was higher than that of surgery after 18 weeks (P<0.05). The premature birth rate of IVF-ET was higher than that of naturally conceived pregnant women (P<0.05). Conclusion: The modified cervical cerclage could effectively prolong the gestational weeks of delivery, reduce the rate of preterm birth, and the operation is simple and easy to promote. It could be used as a surgical option for patients with cervical insufficiency.