[Isolated intraductal carcinoma of the prostate: a clinicopathological and molecular analysis].

Objective: To study the clinicopathological features, immunohistochemical phenotypes, molecular changes, differential diagnosis and prognosis of isolated intraductal carcinoma of the prostate (iIDC-P). Methods: Three iIDC-P cases were collected retrospectively from 2016 to 2022 at Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinicopathologic features and immunophenotypic profiles were studied using light microscopy and immunohistochemistry. A targeted next-generation sequencing panel was used to analyze cancer-associated mutations. Follow-up and literature review were also performed. Results: The patients' ages were 61, 67 and 77 years, and their preoperative prostate specific antigen (PSA) levels were 7.99, 7.99 and 4.86 µg/L, respectively. Case 1 and 2 were diagnosed on needle biopsy and radical prostatectomy (RP) specimens, and case 3 was diagnosed on a specimen of transurethral resection of the prostate (TURP). The RP specimen was entirely submitted for histologic examination. In the case 1, iIDC-P was found in one tissue core (involving two ducts) in the biopsy specimen, and in 6 sections (diameter, 0.3-1.1 cm) from the radical prostatectomy specimen, and one section had separate foci of low-grade acinar adenocarcinoma (diameter, 0.05 cm). In the case 2, 6 tissue sections from the biopsy specimens showed iIDC-P, and 13 sections from RP specimen showed iIDC-P (diameter, 0.5-1.6 cm), and the other 3 sections had separate low grade acinar adenocarcinoma (diameter, 0.6 cm). In the case 3, 5 tissue blocks from the TURP specimen showed iIDC-P. The case 1 and 2 showed solid architecture with expansile proliferation of neoplastic cells in native ducts and acini. The case 3 showed dense or loose cribriform pattern, with marked cytological atypia, and frequent mitotic figures. Comedonecrosis was found in solid or dense cribriform glands in the case 2. Immunohistochemically, surrounding basal cells were highlighted using high-molecular-weight cytokeratin (34ßE12 and CK5/6) and p63, while P504s was positive in the tumor cells. The tumor cells were also positive for AR and prostate markers (NKX3.1, PSA and PSAP), and negative for GATA3. The iIDC-P and acinar adenocarcinoma both showed weak PTEN expression and no ERG (nuclear) expression. In case 2 and 3, targeted sequencing revealed activated oncogenic driver mutations in MAPK and PI3K pathway genes (KRAS, MTOR and PTEN). In addition, pathogenic mutation in TP53 and FOXA1 mutation were found in the case 2 and 3, respectively. No case demonstrated TMPRSS2::ERG translocation. All cases were microsatellite stable and had lower tumor mutation burdens (range, 2.1-3.1 muts/Mb). The patients showed no biochemical recurrence or metastasis after follow-up of 16-91 months. Conclusions: iIDC-P is a special type of intraductal carcinoma of the prostate and differs from intraductal carcinoma within high-grade prostate cancer. iIDC-P has unique molecular characteristics and may represent as a molecularly unique in situ tumor of prostate cancer.

Construction and validation of a prediction model for preoperative prediction of Ki-67 expression in endometrial cancer patients by apparent diffusion coefficient.

AIM: Ki-67 is a marker of cell proliferation and is increasingly being used as a primary outcome measure in preoperative window studies of endometrial cancer (EC). This study explored the feasibility of using apparent diffusion coefficient (ADC) values in noninvasive prediction of Ki-67 expression levels in EC patients before surgery, and constructs a nomogram by combining clinical data. MATERIAL AND METHODS: This study retrospectively analyzed 280 EC patients who underwent preoperative magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in our hospital from January 2017 to February 2023. Evaluate the potential nonlinear relationship between ADC values and Ki-67 expression using the nomogram. The included patients were randomized into a training set (n = 186) and a validation set (n = 84). Using a combination of logistic regression and LASSO regression results, from which the four best predictors were identified for the construction of the nomogram. The accuracy and clinical applicability of the nomogram were assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The results of this study showed a nonlinear correlation between ADCmin and Ki-67 expression (nonlinear P = 0.019), and the nonlinear correlation between ADCmean and Ki-67 expression (nonlinear P = 0.019). In addition, this study constructed the nomogram by incorporating ADCmax, International Federation of Gynecology and Obstetrics (FIGO), and chemotherapy. The area under the curve (AUC) values of the ROC for nomogram, ADCmax, FIGO, chemotherapy and grade in the training set were 0.783, 0.718, 0.579, 0.636, and 0.654, respectively. In the validation set, the AUC values for nomogram, ADCmax, FIGO, chemotherapy, and grade were 0.820, 0.746, 0.558, 0.542, and 0.738, respectively. In addition, the calibration curves and the DCA curves suggested a better predictive efficacy of the model. CONCLUSION: A nomogram prediction model constructed on the basis of ADCmax values combined with clinical data can be used as an effective method to noninvasively assess Ki-67 expression in EC patients before surgery.

[Effect of autologous platelet-rich plasma perfusion on cytokines in uterine drainage fluid of patients with intrauterine adhesions following hysteroscopic adhesiolysis].

Objective: To investigate the effect of autologous platelet-rich plasma (PRP) perfusion on the levels of cytokines in uterine drainage fluid in patients with moderate to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Methods: Thirty patients with moderate to severe IUA who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from November 2020 to March 2021 were randomly divided into two groups: the PRP group (15 patients with placement of intrauterine-suitable balloons and PRP infusion) and the control group (15 patients with placement of intrauterine-suitable balloons only). For all patients, the channel switch was opened 48 hours after the surgery. The drainage fluid of the uterine cavity was collected using syringes through the proximal end of the drainage channel switch at 24 hours after the surgery and through the drainage channel directly at 48, 72, 96, and 120 hours after the surgery, and the levels of related cytokines including platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1) and transforming growth factor-ß1 (TGF-ß1) in the drainage fluid of the uterine cavity were evaluated, respectively. Results: (1) The changes in volumes of uterine cavity drainage fluid: the total drainage fluid volumes of the PRP group and the control group in 120 hours after the surgery were (21.8±2.9) and (22.7±2.7) ml, respectively, and there was no statistically significant difference between the two groups (t=-0.847, P>0.05). No significant differences were found in the volumes of drainage fluid between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). (2) Variation in cytokine levels in the uterine cavity drainage fluid: ① PDGF-BB: median PDGF-BB levels at 24 and 48 hours after the surgery in the PRP group (6.6 and 9.6 µg/L, respectively) were significantly higher than those in the control group (4.7 and 2.7 µg/L, respectively; all P<0.05). There were no significant differences in PDGF-BB levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ② VEGF-A: median VEGF-A levels at 24 and 48 hours after the surgery in the PRP group (3.5 and 2.8 µg/L, respectively) were significantly higher than those in the control group (1.6 and 1.2 µg/L, respectively; all P<0.05). There were no significant differences in VEGF-A levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ③ IGF-1: median IGF-1 level at 48 hours after the surgery in the PRP group was significantly higher than that in the control group (39.5 vs 8.6 µg/L, P<0.05). No significant differences were found in IGF-1 levels at 24, 72, 96, and 120 hours after the surgery between the two groups (all P>0.05). ④ TGF-ß1: There were no significant differences in TGF-ß1 levles between the two groups at 24, 48, 72, 96, and 120 hours after the surgery (all P>0.05). Conclusions: PRP perfusion following hysteroscopic adhesiolysis may increase the levels of PDGF-BB, VEGF-A, and IGF-1 in the uterine cavity drainage fluid, which plays a beneficial role in improving wound microvascular formation, reducing adhesion reformation, and promoting endometrial regeneration and repair.

The value of 3D printing model combined PCNL in kidney stones: a systematic review and meta-analysis.

INTRODUCTION: With the continuous advancement of medical imaging, 3D printing technology is emerging. This technology allows for the representation of complex objects in a model form. This research aims to delve into the irreplaceable value of percutaneous nephrolithotomy (PCNL) in conjunction with 3D printed models in urinary stone surgery. This forward-looking approach provides doctors with a new perspective, enabling them to plan and execute surgeries with greater precision, ultimately delivering a safer and more efficient treatment experience for patients. We evaluated the literature on PCNL for the kidney stones with the introduction of 3D printing models and conducted a meta-analysis. The assessed parameters included stone clearance rate, operation time, hospital stay, blood loss, puncture accuracy, and the rate of complications. EVIDENCE ACQUISITION: We systematically searched the EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases for articles related to PCNL (Percutaneous Nephrolithotomy) with 3D printing models from January 2000 to January 2023. Data were managed and screened using Excel . Meta-analysis was performed for operation time, stone clearance rate, blood loss, puncture accuracy, length of hospital stay, and complications in PCNL combined with 3D printing model for kidney stone treatment. The quality of included articles was assessed using the risk of bias tool by the Cochrane Collaboration. Sensitivity analysis was conducted to assess the reliability of the results. Data were recorded using StataSE 17 software, and publication bias was examined using Egger's linear regression test. EVIDENCE SYNTHESIS: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to conduct a systematic search and screening of literature relevant to the use of 3D printed models in the treatment of kidney stones. We conducted an extensive literature search across several major academic databases, including EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases, to ensure comprehensive coverage of relevant studies. Following the PRISMA process of screening and analysis, we ultimately included 10 randomized controlled trials with a combined sample of 608 for systematic review. CONCLUSIONS: Across these studies, we identified the introduction of 3D printing models prior to surgery for kidney stones resulted in significant advantages for the experimental group compared to the control group in terms of operation time, stone clearance rates, puncture accuracy, hospital stay, blood loss, and the incidence of complications, providing valuable insights for further research and clinical practice.

[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.

Medulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available. Tumor hypoxia and the resulting metabolism are known to be important in the growth and survival of tumors but, to date, have been only minimally explored in MB. Here we show that Group 3 MB tumors do not depend on the canonical transcription factor hypoxia-inducible factor-1α (HIF-1α) to mount an adaptive response to hypoxia. We discovered that HIF-1α is rendered inactive either through post-translational methylation, preventing its nuclear localization specifically in Group 3 MB, or by a low expression that prevents modulation of HIF-target genes. Strikingly, we found that HIF-2 takes over the role of HIF-1 in the nucleus and promotes the activation of hypoxia-dependent anabolic pathways. The exclusion of HIF-1 from the nucleus in Group 3 MB cells enhances the reliance on HIF-2's transcriptional role, making it a viable target for potential anticancer strategies. By combining pharmacological inhibition of HIF-2α with the use of metformin, a mitochondrial complex I inhibitor to block respiration, we effectively induced Group 3 MB cell death, surpassing the effectiveness observed in Non-Group 3 MB cells. Overall, the unique dependence of MB cells, but not normal cells, on HIF-2-mediated anabolic metabolism presents an appealing therapeutic opportunity for treating Group 3 MB patients with minimal toxicity.

Comparative analysis of three-dimensional and two-dimensional models for predicting the malignancy probability of subsolid nodules.

AIM: To construct three-dimensional (3D) and two-dimensional (2D) models to predict the malignancy probability of subsolid nodules (SSNs) and compare their effectiveness. MATERIALS AND METHODS: A total of 371 SSNs from 332 patients, collected between January 2020 and January 2024, were included in the study. The SSNs were divided into a training set for constructing the models and a test set for validating the models. Models were developed using binary logistic backward regression, based on factors that showed significant differences in univariate analyses. The performance of the models was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC). The AUCs of different models were compared using the DeLong test. RESULTS: The AUCs for the two 3D models, one 2D model, and the Brock model were 0.785 (0.733-0.836), 0.776 (0.723-0.829), 0.764 (0.710-0.818), and 0.738 (0.679-0.798) in the training set. In the test set, these AUCs were 0.817 (0.706-0.928), 0.796 (0.679-0.913), 0.771 (0.647-0.895), and 0.790 (0.678-0.903). The two 3D models demonstrated statistically significant differences from the Brock model in the training set (P=0.024 and P=0.046). None of the four models showed significant differences in the test set (all P>0.05). CONCLUSION: The 3D models outperform both the 2D model and the Brock model in predicting the malignancy probability of SSNs, and the 3D model incorporating volume, mean CT attenuation value, and lobulation as factors performed the best.

[Relationship between amniotic fluid inflammatory factors and pregnancy outcomes after emergency cervical cerclage].

Objective: To explore the relationship between amniotic fluid and peripheral blood inflammatory factors and the pregnancy outcomes after emergency cervical cerclage, and to identify effective indicators for predicting adverse pregnancy outcomes after the procedure. Methods: A case-control study was conducted, including pregnant women who were hospitalized at Sun Yat-sen Memorial Hospital, from January 1, 2013, to July 31, 2019, and underwent emergency cervical cerclage due to cervical dilatation at gestational age between 16 and 28 weeks. A total of 85 pregnant women who underwent amniocentesis for the detection of amniotic fluid inflammatory factors during the perioperative period were included. Based on whether their baby was perinatal death, the participants were divided into the case group (28 cases with perinatal death) and the control group (57 cases with live births). Univariate logistic regression analysis was performed to identify risk factors associated with adverse pregnancy outcomes, followed by multivariate logistic regression analysis to establish a regression model and nomogram. Results: (1) The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10 in the amniotic fluid during the perioperative period and postoperative serum C-reactive protein (CRP) were significantly higher in the case group compared to the control group (all P<0.05). The case group underwent emergency cervical cerclage at an earlier gestational age compared to the control group, and their cervical dilation was greater than that of the control group (all P<0.05). However, there were no significant differences in the white blood cell counts, neutrophil percentage, and the level of preoperative CRP in the peripheral blood of pregnant women during the perioperative period (all P>0.05). (2) Univariate logistic regression analysis showed that the levels of amniotic fluid WBC, TNF-α, IL-1ß, IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, postoperative CRP in the peripheral blood, gestational age at cerclage and cervical dilation were associated with adverse pregnancy outcomes (all P<0.05). Multivariate regression analysis indicated that only the levels of amniotic fluid WBC and TNF-α were independent risk factors for perinatal death. (3) Based on clinical practice, a multivariate logistic regression model was constructed including the levels of amniotic fluid TNF-α, WBC, gestational age at cervical cerclage, and cervical dilation. A nomogram and calibration curve were plotted, which suggested its good predictive value for adverse pregnancy outcomes. Conclusions: During the perioperative period of emergency cervical cerclage, the levels of amniotic fluid WBC, TNF-α, IL-1ß, IL-2R, IL-6, IL-8, IL-10 are associated with adverse pregnancy outcomes, with amniotic fluid WBC and TNF-α showing the closest relationship. However, there is no significant correlation between maternal peripheral hemogram during the perioperative period and adverse pregnancy outcomes. A model constructed by amniotic fluid TNF-α, WBC, cervical cerclage gestational age, and cervical dilation has a good predictive effect on adverse pregnancy outcomes.

[Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing].

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

Associations and Potential Multiple Mechanisms between Subjective Hearing Loss and Cognitive Impairment.

BACKGROUND: Subjective hearing loss (SHL) refers to an individual's self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation. OBJECTIVES: To validate potential mechanisms between SHL and cognitive impairment. DESIGN: Cross-section. SETTING: Shanghai, China. PARTICIPANTS: A total of 2369 individuals from communities and the cognitive disorder clinic. MEASUREMENTS: All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants' brain ß-amyloid (Aß) deposition status, plasma biomarkers associated with Alzheimer's disease (AD), and cardiovascular risk factors were also collected. RESULTS: In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aß deposition, SHL demonstrated associations with cognitive function independent of plasma Aß42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status. CONCLUSION: SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.

Logistic regression model predicts early surgical site infection after spinal fusion: a retrospective cohort study.

OBJECTIVE: This study aimed to develop a diagnostic model for predicting early surgical site infection (SSI) based on postoperative inflammatory markers after spinal fusion surgery. METHODS: In this retrospective study, we analysed the trends of inflammatory markers between SSI and non-SSI groups. The data were randomly divided into training cohort and validation cohort (ratio 7:3). The variables for SSI were analysed using stepwise logistic regression to develop the prediction model. To evaluate the model, we analysed its sensitivity, specificity, positive predictive value, negative predictive value, as well as the area under the curve in the validation cohort. Calibration plots and decision curve analysis were employed to assess the calibration and clinical usefulness of the model. FINDINGS: We observed significant changes in inflammatory markers on the seventh day after surgery. The prediction model included four variables on the seventh day after surgery: body temperature, C-reactive protein, erythrocyte sedimentation rate and neutrophil counts. After binary processing of these data, the simplified model achieved an area under the curve of 0.86 (95% confidence interval (CI): 0.81-0.92) in the training cohort and 0.9 (95% CI: 0.82-0.98) in the validation cohort. Calibration plots and decision curve analysis demonstrated that the proposed model was effective for the diagnosis of SSI. CONCLUSION: We developed and validated a prediction model for diagnosing early infection after spinal fusion.

[Short-term efficacy and safety of cardiac contractility modulation in patients with heart failure].

Objective: To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure. Methods: This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded. Results: CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions: CCM has better short-term safety and efficacy in patients with heart failure.

Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant status, and immune responses of lactating donkeys.

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 yr of BW ± SD), weight (250.06 ± 25.18 kg), DIM (39.11 ± 7.42 d), and average parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 wk for adaptation, and 8 wk for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including DMI, milking yield, estimated milk yield, solids-corrected milk, ECM, milk fat yield, milk protein yield, milk lactose yield, milk TS yield, and milk SNF yield. The digestibility of DM, CP, ADF, and NDF was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of IgA, IgG, and IgM, the activities of the superoxide dismutase, catalase, and total antioxidant capacity in the serum. Artemisia ordosica crude polysaccharides decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites l-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, lysophosphatidylcholine (LysoPC) (18:0), LysoPC (18:1(9Z)), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.

[Inhibition of glutamatergic neurons in the dorsomedial periaqueductal gray alleviates excessive defensive behaviors of mice with post-traumatic stress disorder].

OBJECTIVE: To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey (dmPAG) in regulating excessive defensive behaviors in mice with post-traumatic stress disorder (PTSD). METHODS: Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno- associated viral vectors (rAAV2/9-CaMKII-mCherry, rAAV2/9-CaMKII-hM3Dq-mCherry and rAAV2/9-CaMKII-hM4Di-mCherry) into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons, followed 2 weeks later by PTSD modeling by single prolonged stress. The looming test, response to whisker stimulation test and contextual fear conditioning (CFC) test were used to observe changes in defensive behaviors of the PTSD mice. The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining. RESULTS: Compared with the control mice, the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest, response scores of defensive behaviors and freezing time (all P<0.01). Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors. Activation of the glutamatergic neurons in the dmPAG (in PTSD hM3Dq group) did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice, whereas inhibiting the glutamatergic neurons in the dmPAG (in PTSD hM4Di group) caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice (P<0.05 or 0.01). CONCLUSION: Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

[Progress in research of rash and fever syndrome surveillance and early warning].

Objective: To introduce the progress in research of rash and fever syndrome (RFS) surveillance and early warning both at home and abroad, and provide reference for surveillance and prevention of RFS in China. Methods: The keywords "fever" "rash" and "surveillance" and others were used for a literature retrieval by using China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and Web of Science. The languages of literatures were limited in Chinese and English. The key information of the literatures were collected and analyzed with Excel. Results: A total of 36 study papers (21 in Chinese and 15 in English) were included. The studies mainly focused on the pathogen surveillance of RFS (n=19). The pathogens included measles virus, varicella-zoster virus, rubella virus, enterovirus, human B19 virus, dengue virus, streptococcus group A, Salmonella typhi and Salmonella paratyphoid,human herpesvirus, mumps virus and adenovirus. Eight studies were about the surveillance in major events, such as sport game, World Expo and religious gathering, or sudden natural disasters, such as earthquake and tropical storm, during 2010-2015. Eight studies focused on case or epidemic surveillance, most of which were studies from other counties. The surveillance sites were medical institutions. RFS was diagnosed according to the International Classification of Diseases, 9th (ICD-9) and symptoms descripted in chief-complaint. Only one study in Mongolia conducted RFS epidemic prediction. The analysis methods of 36 papers included simple descriptive analysis, time-based early warning models (such as regression analysis, fixed threshold method, Hugh Hart control chart method and cumulative sum control chart method) and time series analysis method. Conclusions: In the future, RFS surveillance system should cover both known pathogens and emerging pathogens. Automatic surveillance using information capture and intelligent modelling can be applied to improve the sensitivity and specificity of RFS surveillance and early warning.

[Efficacy of combined treatment with pirfenidone and PD-L1 inhibitor in mice bearing ectopic bladder cancer xenograft].

OBJECTIVE: To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation. METHODS: Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group, PD-L1 inhibitor group, pirfenidone group and combined treatment group (n=10). After successful modeling, PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days, and oral pirfenidone (500 mg/kg) was given on a daily basis. The survival rate of the mice and tumor growth rate were compared among the 4 groups. The expressions of CD3, CD8, CD45, E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment, and bone marrow-derived suppressor cells (MDSCs) were observed with immunofluorescence staining; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), creatinine (CRE) and lactate dehydrogenase (LDH-L) were analyzed using an automated biochemical analyzer. RESULTS: Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days (P < 0.05), but the combined treatment produced an obviously stronger inhibitory effect (P < 0.05). PD-L1 inhibitor and pirfenidone alone significantly increased E- cadherin expression and decreased N-cadherin expression in the tumor tissue (P < 0.05). The two treatments both significantly increased the percentage of CD3+, CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue, and these changes were more obvious in the combined treatment group (P < 0.05). No significant differences were found in serum ALT, AST, BUN, CRE or LDH-L levels among the 4 groups (P>0.05). CONCLUSION: Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.

[Clinical effect of superior oblique re-tucking for recurrent or residual compensatory head position].

Objective: To evaluate the effects of re-tucking the superior oblique muscle on recurrent or residual compensatory head position. Methods: A retrospective case series study was conducted. 12 recurrent or residual compensatory head position patients (12 eyes) with congenital superior oblique palsy who underwent superior oblique re-tucking in Tianjin Eye Hospital from March 2015 to February 2021 were included. All patients had a history of superior oblique tucking procedure and showed signs of superior oblique muscle palsy without inferior oblique muscle overaction. During surgery, the Guyton forced duction test is used to evaluate the relaxation of the superior oblique muscle tendon, which affects the re-tucking length of the muscle.Their head position, vertical deviation, eye movement, fovea-disa angle, and Bielschowsky head tilt test were assessed pre-and post-surgery. Statistical analysis was performed using ttest and paired samples Wilcoxon signed rank test. Results: Out of the 12 patients, 8 were male and 4 were female, aged between 2 and 9 years. The initial surgery was done at age 6, with a superior oblique recession length of (7.17±1.03) mm. Recurrent head tilt occurred in 11 patients after (3.82±0.98) months postoperatively, and 1 patient had residual head tilt, with a followup period of six months or more. Ocular motility examination revealed underaction of the superior oblique muscle, positive Bielschowsky's head tilt test, and Guyton forced duction tese indicating relaxation of the paralyzed superior oblique muscle tendon. Scar adhesion was observed at the stop of the superior oblique muscle, as well as the previous sutures. The scar and the sutures around the stop of the superior oblique muscle were released, the mean re-tucking amount was(7.83±1.59)mm. Follow-up at 12 to 18 months postoperatively showed disappearance of compensatory head position, significant improvement in superior oblique muscle lag, normal ocular motility, and no occurrence of Brown syndrome. The results of Bielschowsky head tilt were negative in 9 cases and still positive in 3 cases after superior oblique re-tucking. The primary vertical deviation was 2.5 (2.0, 5.3) prism diopter pre-operatively and 1 (0, 1) prism diopter post-operatively, respectively. The difference was statistically significant (U=6.00, P<0.001). The total amount of FDA in both eyes was (-22.04±5.47)° and (-15.27±6.08)° pre-and post-operatively, respectively. The difference was statistically significant (t=2.87, P=0.009). All 12 patients have normal eye movement after superior oblique re-tucking procedure. All patients had no compensatory head position at last follow-up. Conclusions: Superior oblique re-tucking is suitable for patients with relaxation of the superior oblique muscle tendon and extrocular rotation as the main sign. It can effectively and safely correct the recurrent or residual compensatory head position after re-tucking the superior oblique muscle.