The relationship between uric acid and bone mineral density in the intermediate stage of CKD 1-3.

BACKGROUND: Some studies have suggested that uric acid has antioxidant properties that can prevent bone loss, but the relationship between uric acid and bone mineral density is controversial. The aim of this study was to investigate the relationship between UA and BMD in patients with CKD stage 1-3. METHODS: We extracted 13,047 participants from the NHANES database, including 7342 male subjects and 5705 female subjects. Weighted multiple linear regression analysis was used to investigate the correlation between UA and BMD in patients with CKD stages 1-3. RESULTS: In patients with CKD stage 1-3, UA was significantly correlated with BMD. In the male group, UA was positively associated with BMD (ß, 7.94 [95%CI, 4.95, 10.94]). In the female group, there was a negative relationship between them (ß, -5.33 [95%CI, -8.77, -1.89]). The relationship between UA and BMD in male group showed an inverted U-shaped curve, and UA was positively correlated before 6.1 mg/dl and negatively correlated after 6.1 mg/dl. The relationship was basically negative in the female group. CONCLUSIONS: For the patients with CKD stage 1-3, the relationship between UA and BMD showed an inverted U-shaped curve in the males, while the relationship was largely negative in the females.

Construction and validation of a nomogram for predicting disease-free survival after radical resection of rectal cancer using perioperative inflammatory indicators.

Background: Colorectal cancer is a common digestive tract malignancy that seriously affects patients' quality of life and survival time. Surgery is the main treatment modality, but postoperative prognosis varies greatly. This study sought to explore the impact of perioperative inflammatory indicators on disease-free survival (DFS) in patients after radical resection of rectal cancer and to construct a nomogram for clinical reference. Methods: A retrospective analysis was performed on 304 primary rectal adenocarcinoma patients who underwent laparoscopic radical resection of rectal cancer at the Affiliated Hospital of Xuzhou Medical University from May 1, 2018 to September 30, 2020. The patients were divided into a training set (n=213) and a validation set (n=91) at a ratio of 7:3. The cut-off values of each inflammatory indicator based on the receiver operating characteristic (ROC) curve were determined and each indicator was divided into high and low groups. The least absolute shrinkage and selection operator (LASSO)-Cox regression model was used to analyze the independent risk factors affecting DFS, and a nomogram was established. The model was internally validated using the validation set, and the discrimination, calibration, and clinical application value of the nomogram were evaluated using ROC curve, calibration curve, and clinical decision curve analysis (DCA). Results: Tumor-node-metastasis (TNM) stage III, neural invasion, preoperative neutrophil-to-lymphocyte ratio (NLR) ≥1.995, postoperative systemic immune-inflammation index (SII) ≥451.05, and Δpan-immune-inflammation value (ΔPIV) ≥144.36 (P<0.05) were independent factors for predicting the 3-year DFS of patients after rectal cancer surgery. The area under the ROC curve (AUC) of the nomogram was 0.811 [95% confidence interval (CI): 0.778-0.889] in the training set and 0.808 (95% CI: 0.785-0.942) in the validation set. The nomogram showed good calibration, indicating good consistency between predicted and actual risks. DCA demonstrated the clinical utility of the nomogram. Conclusions: The nomogram constructed based on TNM stage III, neural invasion, preoperative NLR ≥1.995, postoperative SII ≥451.05, and ΔPIV ≥144.36 can predict the risk of 3-year DFS in patients undergoing curative surgery for rectal cancer, enabling strict postoperative follow-up and timely adjuvant treatment for high-risk patients.

Prognostic value of preoperative combined with postoperative systemic immune-inflammation index for disease-free survival after radical rectal cancer surgery: a retrospective cohort study.

Background: Colorectal cancer (CRC) ranks highly in malignant tumor incidence and mortality rates, severely affecting human health. The predictive value of the systemic immune-inflammation index (SII) in CRC prognosis is gaining attention, but there is limited research on the combined preoperative and postoperative SII. This study aims to explore the prognostic value of combined SII on disease-free survival (DFS) in patients undergoing radical surgery for rectal cancer. Methods: We enrolled 292 patients with rectal cancer who underwent radical resection at the Affiliated Hospital of Xuzhou Medical University from May 2018 to September 2020, along with regular follow-ups to document the DFS. Patients' complete blood cell counts were assessed before surgery and between 21-56 days postoperatively. Calculating preoperative and postoperative SII, patients were categorized into four groups based on the optimal cutoff values: (I) low-low group (preoperative SII <449.325 and postoperative SII <568.13); (II) high-low group (preoperative SII ≥449.325 and postoperative SII <568.13); (III) low-high group (preoperative SII <449.325 and postoperative SII ≥568.13); and (IV) high-high group (preoperative SII ≥449.325 and postoperative SII ≥568.13). The receiver operating characteristic (ROC) curve analysis evaluated the prediction efficacy of preoperative, postoperative, and combined SII. Kaplan-Meier analysis generated DFS curves, and Cox regression analysis determined prognostic factors. Results: With a median follow-up of 41 months, 65.4% (191/292) patients reached DFS. The clinical pathological features between the four groups are balanced and comparable (P>0.05). The area under the ROC curve for preoperative, postoperative, and combined SII was 0.668 [95% confidence interval (CI): 0.6-0.737], 0.696 (95%CI: 0.63-0.763), and 0.741 (95% CI: 0.681-0.802), respectively. After adjusting for confounding factors such as adjuvant therapy, differentiation, vascular invasion, neural invasion, tumor-node-metastasis (TNM) stage, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), significant differences were observed between the high-low group [hazard ratio (HR) =2.403; 95% CI: 1.255-4.602; P=0.008], low-high group (HR =5.058; 95% CI: 2.389-10.71; P<0.001), and high-high group (HR =6.214; 95% CI: 3.474-11.115; P<0.001) compared to the low-low group, with higher risks of adverse outcomes. Conclusions: Combined SII has better predictive efficacy than monitoring preoperative or postoperative SII alone in rectal cancer patients undergoing radical surgery.

Real-world study of trastuzumab and pertuzumab combined with chemotherapy in neoadjuvant treatment for patients with HER2-positive breast cancer.

Clinical trials have shown that trastuzumab (H) and pertuzumab (P) combined with chemotherapy as neoadjuvant therapy increased pathological complete response (pCR) rate of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, date in China in the real world are currently limited. Clinical data from patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy at 2 institutions from March 2019 to February 2022 were retrospectively analyzed. Adverse reactions were evaluated using CTCAE version 5.0. The primary endpoint was total pathologic complete response (tpCR; ypT0/isypN0), and the secondary endpoints were breast pathologic complete response (bpCR; ypT0/is) and axillary pathologic complete response (apCR; ypN0). Factors influencing tpCR were also analyzed. A total of 302 patients were included in the analysis, of which 145 were treated with H + P + taxane + carboplatin (TcbHP), 94 with H + P + taxane (THP) and 63 with sequential anthracycline and cyclophosphamide, followed by H + P + taxane (AC-THP). The overall tpCR rate was 64.9%, and those of TcbHP, THP, and AC-THP were 73.1%, 52.1%, and 65.1%, respectively. The tpCR rate of the hormone receptor (HR) negative group (80.3%) was higher than that of the HR positive group (52.1%). The overall bpCR rate was 73.5% and the apCR rate was 75.8%. In the univariate analysis, HR, HER2 status and treatment regimen were related factors that affected tpCR. In the multivariate analysis, HR, HER2 status and treatment regimen were independent predictors of tpCR (P < .001, P < .001 and P = .009). The levels 3 and 4 toxicities rates of TcbHP were slightly higher than those of THP and AC-THP. HP combined with chemotherapy has achieved a high pCR rate. The TcbHP regimen had the highest pCR. HR-negative tumors demonstrated a higher pCR. HR, HER2 status and treatment regimen were independent predictors of tpCR. The adverse reactions are controllable.

Increased perihematomal neuron autophagy and plasma thrombin-antithrombin levels in patients with intracerebral hemorrhage: An observational study.

Animal studies have demonstrated that autophagy was involved in neuronal damage after intracerebral hemorrhage (ICH). Several studies showed thrombin-antithrombin (TAT) plasma levels were elevated in patients with ICH. In this study, we aimed to evaluate if autophagy occurred in patients with ICH; and the relationship between the severity of brain injury and plasma TAT levels.A novel tissue harvesting device was used during hematoma removal surgery to collect loose fragments of tissue surrounding the affected brain area in 27 ICH patients with hematoma volumes of >30 mL in the basal ganglia. Control tissues were obtained from patients who underwent surgery for arteriovenous malformation (n = 25). Transmission electron microscopy (TEM) and immunohistochemistry for autophagy-related proteins were used to evaluate the ultrastructural and morphologic cellular characteristics; and the extent of autophagy in the recovered tissue specimens. Stroke severity was assessed by using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TAT levels.Transmission electron microscopy showed autophagosomes and autolysosomes exist in neurons surrounding the hematoma, but not in the control tissues. The number of cells containing autophagic vacuoles correlated with the severity of brain injury. Immunohistochemistry showed strong LC3, beclin 1, and cathepsin D staining in ICH tissue specimens. Plasma TAT levels correlated positively with autophagic cells and ICH severity (P < .01).Autophagy was induced in perihematomal neurons after ICH. Autophagy and plasma TAT levels correlated positively with severity of brain injury. These results suggest that autophagy and increased plasma TAT levels may contribute to the secondary damage in ICH patients.

A cross-sectional study to investigate the correlation between depression comorbid with anxiety and serum lipid levels.

BACKGROUND: Depression is a common psychological disorder that severely threatens human health. Its pathology remains unclear, but it has been suggested to be associated with abnormal blood lipid metabolism. OBJECTIVES: This study aimed to explore the changes in blood lipid levels in patients with depression accompanied or not by anxiety, and assess whether adjusting the clinical therapeutic strategy could be based on blood lipid test results, providing a novel insight into depression treatment. METHODS: This was a cross-sectional study. We assessed 60 outpatients and inpatients diagnosed with depression from January 2013 to January 2014 who met the Chinese Classification of Mental Disorders version 3 (CCMD-3) criteria, with Hamilton Rating Scale for Depression (HAMD-24) ≥20. They were grouped into depression with anxiety (n=29) and depression without anxiety (n=31) groups by the Hamilton Anxiety Scale (HAMA). RESULTS: TG levels were higher in the depression with anxiety group compared with patients without anxiety (P=0.045), which was confirmed by multifactorial analysis [P=0.017, OR=4.394, 95% CI (1.303-14.824)]. A negative correlation between anxiety score and HDL levels was observed in patients with depression (r=-0.340, P=0.046). Meanwhile, positive associations were obtained between retardation and LDL levels (r=0.307, P=0.017) as well as age at disease onset and total cholesterol levels (r=0.410, P=0.002). CONCLUSION: TG levels differ in patients with depression accompanied by anxiety compared with those without anxiety.

Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage.

Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH.

[Analysis of thrombin-antithrombin complex expressions in the plasma and the hematoma fluid of intracerebral hemorrhage patients of excess syndrome of stroke and depletion syndrome of stroke].

OBJECTIVE: To study the relationship between the expressions of thrombin-antithrombin (TAT) complex and excess syndrome of stroke (ESS) and depletion syndrome of stroke (DSS) by dynamically observing the expressions of TAT complex in the plasma and hematoma fluid of intracerebral hemorrhage (ICH) patients. METHODS: Sixty patients were assigned to three groups according to syndrome typing, i.e., as yang excess group (18 cases), yin excess group (22 cases), and depletion syndrome group (20 cases). The hemorrhage volume was assessed. NIHSS and GCS were scored. Besides, 30 healthy volunteers at the Physical Examination Center, Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine were recruited as the normal control group. Another 10 patients in need of lumbal anesthesia were recruited as the cerebrospinal fluid control group, who suffered from surgical, gynecologic pelvic diseases, or diseases from lower limbs, but unaccompanied with cardio-/cerebrovascular diseases. The expressions of TAT complex were detected in the venous blood and hematoma fluid of the patient groups and in the venous blood or the cerebrospinal fluid of the control group using ELISA. RESULTS: The syndromes were sequenced as the depletion syndrome > the yin excess syndrome > the yang excess syndrome according to the hemorrhage volume and NIHSS score. They were sequenced as the yang excess syndrome > the yin excess syndrome >the depletion syndrome according to the GCS score. The plasma TAT complex content on the 4th day in the ICH group was lower than that at the rest time points, showing statistical significance (P<0.01). Compared with the normal control group, the plasma TAT complex on the 1st, 2nd, and 4th day all increased with statistical difference (P<0.01). Statistical significance of the TAT complex in the hematoma fluid of the ICH group existed when compared it on the 1st, 2nd, and 4th day (P<0.01). Compared with the cerebrospinal fluid control group, the contents of the TAT complex in the hematoma fluid of the ICH group increased with statistical difference (P<0.01). The hemorrhage volume of ICH patients was positively correlated with NIHSS (r=0.809, P<0.01) and negatively correlated with GCS (r=-0.833, P<0.01). The TAT complex was obviously higher in the ICH group than in the two control groups in a dynamic way (P<0.01). There was obvious difference in the expressions of TAT among yang excess group, yin excess group, and depletion syndrome group (P<0.01). The expressions of TAT in the plasma and the hematoma fluid of the ICH group were negatively correlated with GCS score and positively correlated with NIHSS score (both P<0.01). CONCLUSIONS: TAT complex participated in secondary neuron injury after ICH, which could be taken as an objective index for clinical observation. It also could provide evidence for syndrome quantification of excess syndrome and depletion syndrome.

Morphological and photosynthetic variations in the process of spermatia formation from vegetative cells in Porphyra yezoensis Ueda (Bangiales, Rhodophyta) and their responses to desiccation.

Porphyra yezoensis has a macroscopic foliage gametophyte phase with only a single cell layer, and is ideally suited for the study of the sexual differentiation process, from the vegetative cell to the spermatia. Firstly, we compared variations in the responses of the vegetative and male sectors to desiccation. Later, cell tracking experiments were carried out during the formation of spermatia from vegetative cells. The two sectors showed similar tolerance to desiccation, and the formation of spermatia from vegetative cells was independent of the degree of desiccation. Both light and scanning electron microscopy (SEM) observations of the differentiation process showed that the formation of spermatia could be divided into six phases: the one-cell, two-cell, four-cell, eight-cell, pre-release and spermatia phases. Photomicrographs of Fluorescent Brightener staining showed that the released spermatia had no cell walls. Photosynthetic data showed that there was a significant rise in Y(II) in the four-cell phase, indicating an increase in photosynthetic efficiency of PSII during this phase. We propose that this photosynthetic rise may be substantial and provide the increased energy needed for the formation and release of spermatia in P. yezoensis.

VARIATIONS IN THE CELL WALLS AND PHOTOSYNTHETIC PROPERTIES OF PORPHYRA YEZOENSIS (BANGIALES, RHODOPHYTA) DURING ARCHEOSPORE FORMATION(1).

The formation of archeospores is characteristic of Porphyra yezoensis Ueda and is important for Porphyra aquaculture. Recently, it has been regarded as a valuable seed source for propagation of thalli in mariculture. Cell wall composition changes are associated with archeospore formation in P. yezoensis. Here, we report changes of cell walls of P. yezoensis during archeospore formation. The surfaces of vegetative cells that were originally smooth became rougher and more protuberant as archeosporangia were formed. Ultimately, the cell walls of archeosporangia ruptured, and archeospores were released from the torn cell walls that were left at distal margins of thalli. With changes in cell walls, both effective quantum yield and maximal quantum yield of the same regions in thalli gradually increased during the transformation of vegetative cells to archeospores, suggesting that the photosynthetic properties of the same regions in thalli gradually increased. Meanwhile, photosynthetic parameters for different sectors of thalli were determined, which included the proximal vegetative cells, archeosporangia, and newly released archeospores. The changes in photosynthetic properties of different sectors of thalli were in accordance with that of the same regions in thalli at different stages. In addition, the photosynthetic responses of archeosporangia to light showed higher saturating irradiance levels than those of vegetative cells. All these results suggest that archeosporangial cell walls were not degraded prior to release but were ruptured via bulging of the archeospore within the sporangium, and ultimately, archeospores were discharged. The accumulation of carbohydrates during archeospore formation in P. yezoensis might be required for the release of archeospores.

Overexpression of 14-3-3σ counteracts tumorigenicity by positively regulating p73 in vivo.

14-3-3σ, one of the 14-3-3 family members, was initially identified as a human mammary epithelium-specific marker 1. The expression of 14-3-3σ is directly regulated by p53. It has been demonstrated that 14-3-3σ stabilizes p53 and enhances its transcriptional activity through the interaction with p53, suggesting that 14-3-3σ has a positive feedback effect on p53. Our previous study showed that 14-3-3σ is a direct transcriptional target of p73 and enhances the p73-mediated transcriptional as well as pro-apoptotic activity in vitro. In the present study, we explored the tumor-suppressive effect of 14-3-3σ by establishing a breast cancer xenograft nude mouse model with an inducible expression of 14-3-3σ or with an inducible expression of p53/p73 plus 14-3-3σ with ADR treatment. Tumor formation was then assayed. Moreover, 66 primary breast cancer specimens and paired tumor-free breast specimens obtained from the female patients were examined. Results showed that the expression of p73 and 14-3-3σ in breast cancer specimens was significantly lower than the tumor-free breast specimens and that 14-3-3σ expression was positively correlated with the expression of p73. Furthermore, overexpression of 14-3-3σ counteracts tumorigenicity by positively regulating p73 in p53-mutated or -deficient cancers in vivo. Therefore, our results may lead to the use of 14-3-3σ in the therapeutic application for the p53-mutated and p73-expressed breast cancer patients.

[Expression of matrix metalloproteinase MMP-9 in the plasma and hematoma fluid of intracerebral hemorrhage patients].

OBJECTIVE: To investigate the matrix metalloproteinase (MMP)-9 played in secondary brain injury following intracerebral hemorrhage (ICH). METHODS: Hematoma fluid and peripheral blood samples were collected from 60 ICH patients, 34 males and 26 females, aged 60 +/- 13 (37 - 81) n the days 1, 4, and 7 after evacuation of hematoma. Peripheral blood samples were collected form. 30 sex, and age-matched healthy adults as normal controls. Cerebrospinal fluid (SCF) samples were collected from 10 sex, and age-matched patients to undergo operation during lumbar anesthesia. ELISA was used to detect the content of MMP-9. Tada formula was used to calculate the perihematomal edema volume. The National Institutes of Health Stroke Scale (NIHHS) and Glasgow Coma Score (GCS) were used to assess the condition of patients. RESULTS: (1) The MMP-9 levels in the plasma and hematoma fluid of the ICH patients at all time points were all significantly higher than those of the normal controls (all P < 0.01). MMP-9 was not found in the normal CSF. (2) The plasma and hematoma fluid MMP-9 levels were increased already in the day 1, peaked in the day 4, and then kept at a high level until the day 7. (3) The MMP-9 levels in hematoma fluid t all time points were all significantly higher than those in the plasma (all P < 0.01). (4) The MMP-9 level was positively correlated with the hematoma volume and NIHSS score, and negatively correlated with the GCS score (both P < 0.01). CONCLUSIONS: MMP-9 may takes part in the secondary injury after ICH, and its change is correlated with the hydrocephalus of patients. The dynamical change of the plasma MMP-9 level is consistent with the hematoma fluid MMP-9 level after ICH. There is a positive correlation among the MMP-9 level, perihematomal edema volume, and severity of ICH.