Jiawei Shengjiangsan's Effect on Renal Injury in Diabetic Nephropathy Mice is Investigated via the PI3K/Akt/NF-κB Signaling Pathway.

Purpose: This study aimed to investigate the intervention mechanism of Jiawei Shengjiangsan (JWSJS) on kidney injury in diabetic nephropathy mice. Methods: Thirty 8-week-old db/db mice were randomly divided into five groups: model group, Perindopril group, and JWSJS low-, medium-, and high-dose groups (n=6 per group) based on body weight. Additionally, a blank control group was established consisting of 6 db/m mice aged 8 weeks. The blank and model groups received daily intragastric administration of 7g/kg/d pure water. The remaining groups were assigned to JWSJS low (3.5g/kg/d), medium (7g/kg/d), high (14g/kg/d) dosage groups, and perindopril positive control group (0.48mg/kg/d) for 12 weeks. Post-experiment, serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed using an automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) measured 24-hour urinary albumin, neutrophil gelatinase-associated lipocalin (NGAL), TNF-α, IL-1ß, VCAM-1, MCP-1, and HbA1c. Western blot assessed the protein expressions of p-PI3K, p-Akt, and p-NF-κB p65, while pathological kidney changes were observed. Results: Compared to the blank group, the model group exhibited increased SCr, BUN, 24-hour urinary albumin, serum NGAL, TNF-α, IL-1ß, VCAM-1, MCP-1, HbA1c, p-PI3K, and p-Akt, alongside increased p-NF-κB p65 expression, indicating significant kidney pathology. After treatment, the JWSJS group showed decreased SCr, BUN, 24-hour urinary microalbumin, NGAL, HbA1c, TNF-α, IL-1ß, VCAM-1, MCP-1 levels, increased p-PI3K and p-Akt expression (P<0.05), and reduced p-NF-κB p65 content (P<0.05). Histopathological analysis revealed that JWSJS ameliorated renal tubular epithelial cell damage, glomerular capillary and basement membrane injuries, and facilitated the repair of damaged podocytes in diabetic nephropathy mice. Conclusion: JWSJS demonstrated efficacy in reducing renal inflammation in diabetic nephropathy mice, with its mechanism likely associated with the inhibition of the PI3K/Akt/NF-κB signaling pathway.

The importance of preoperative T3 stage substaging by 3D endorectal ultrasonography for the prognosis of middle and low rectal cancer.

OBJECTIVE: The study aimed to validate the role of 3D-endorectal ultrasonography in prognosis and recurrence for patients with T3-stage rectal cancer by evaluating the preoperative extramural depth of tumor invasion. METHODS: In this study, we investigated the medical records of rectal cancer patients who were admitted to Changhai Hospital's Colorectal Surgery Division. The sample group was categorized into three subgroups (T3a, T3b, and T3c) based on the extent of tumor progression (<5 mm, 5-10 mm, and >10 mm) to assess the endorectal ultrasonography diagnostic performance. The 5-year disease-free survival and overall survival were assessed using the Kaplan-Meier method and a log rank test. Cox regression analysis verified the tumor invasion depth's significance as a prognostic predictor, and it was also utilized to evaluate other independent risk variables for recurrence after surgery. RESULTS: The study included 72 individuals with low and middle rectal cancer from January 2014 to November 2019. Twenty-two individuals had stage T3a, 22 had stage T3b, and 28 had stage T3c based on preoperative endorectal ultrasonography. Endorectal ultrasonography had 88.0%, 86.8%, and 76.2% overall accuracy for stratifying subgroups, respectively. According to the Kaplan-Meier curve, 5-year OS was 100%, 83.5%, and 92.9% for T3a, T3b, and T3c (p = 0.172), and 5-year disease-free survival was 100%, 80.8%, and 72.9% for T3a, T3b, and T3c, respectively (p = 0.014). A distinct risk factor for 5-year disease-free survival was the degree of tumor infiltration (p = 0.039). CONCLUSION: Preoperative T3 stage subdivision allows for categorization of prognosis and survival. Endorectal ultrasonography reports should make explicit declarations of T3a, T3b, and T3c scales.

Effects of Fu's subcutaneous needling on mitochondrial structure and function in rats with sciatica.

To observe the effects of Fu's subcutaneous needling (FSN) and acupuncture treatment on the mitochondrial structure and function of the skeletal muscle tissue of rats with sciatica. Forty Sprague-Dawley rats were divided into control, model, acupuncture, and FSN groups (10 each) according to a random number table. The control group was left untreated. Rats in the FSN group were treated with FSN once every 2 days for three times, respectively (days 1, 3, 5, and 7), to cooperate with reperfusion approach. The acupuncture group was treated at the same timeline as that of the FSN group. Changes in the mechanical pain threshold, mitochondrial ultrastructure, mitochondrial citrate synthase (CS) activities, mitochondrial respiratory chain complex II, and mitochondrial COX- I protein expression in the skeletal muscle of rats treated with different treatments were compared with those of the model group. The pain thresholds of the rats were remarkably higher after FSN treatment and acupuncture, and the pain threshold of the FSN group was higher than that of the acupuncture group. Compared with the control group, the mitochondria of the model group had a damaged ultrastructure, were arranged in a disorganized manner, accumulated under the basement membrane, and appeared vacuolated with autophagosomes. The state of mitochondria in the FSN group was close to that in the control group and was remarkably better than that in the acupuncture group. The activities of mitochondrial CS and respiratory chain complex II in the skeletal muscle of the treated rats decreased compared with the control group (p < 0.05), and their levels were better in the FSN group than in the acupuncture group (p < 0.05). FSN treatment for 1 week considerably improved the pain thresholds and improved the skeletal muscle mitochondrial ultrastructure and mitochondrial function in rats with sciatica.

Protective Mechanism of Proprotein Convertase Subtilisin-Like Kexin Type 9 Inhibitor on Rats with Middle Cerebral Artery Occlusion-Induced Cerebral Ischemic Infarction.

The aim of this study was to research the mechanism of proprotein convertase subtilisin-like kexin type 9 (PCSK9) inhibitor in neural protective effect on rat cerebral ischemic reperfusion injury (I/RI). The transient middle cerebral artery occlusion (tMCAO) model of rats was prepared by the suture method, and PCSK9 inhibitor was injected intraperitoneally immediately after I/R. The rats were scored for neurological deficits and the cerebral infarction volume was measured. The brain tissues were collected and western blot (WB) was used to detect the expression of PCSK9. The rat cortical neural stem cells were treated with oxygen glucose deprivation (OGD) to establish a cell model of ischemia/reperfusion. WB was used to detect the expression of PCSK9 and the apoptosis-related pathway proteins. After interfering with the expression of PCSK9 siRNA, the cell viability (cell counting kit-8 assay) and apoptosis (TUNEL staining, Annexin V/PI method) were detected, and the cell proliferation was detected by EdU staining and flow cytometry. The expression of PCSK9 in the brain tissue of the MCAO group was dramatically increased. PCSK9 inhibitor can improve neurobehavioral scores and reduce apoptosis and infarct volume. An OGD model of neural stem cells in vitro was constructed. Inhibiting PCSK9 with si-PCSK9 can increase cell viability, promote cell proliferation, and also reduce cell apoptosis. Inhibition of PCSK9 can decrease the cerebral infarct volume in rats with cerebral I/RI and improve the neural function. Mechanically, inhibition of PCSK9 can lead to the decrease of nerve cell apoptosis and promotion of cell proliferation.

Implementation of virtual reality technology to decrease patients' pain and nervousness during colonoscopies: a prospective randomised controlled single-blinded trial.

BACKGROUND: Improved patient satisfaction in endoscopy is worthy of study as it is an invasive and potentially uncomfortable procedure. There is growing literature on patient satisfaction assessment in endoscopy as part of improving quality assurance. This study aimed to determine whether virtual reality (VR) technology can decrease patients' pain and nervousness during colonoscopies. METHODS: Patients enrolled without sedation were randomly categorised into groups that watched VR (VR group; n=58) and those that did not watch VR (control group; n=59). The primary outcomes were pain score and skin conductance. Secondary endpoints included heart rate, systolic and diastolic arterial pressures, overall patient satisfaction, willingness to repeat the procedure, the difficulty of the procedure, the procedure duration, and bowel preparation. RESULTS: The median (interquartile range (IQR)) pain scores were 7 (6-8) and 5 (4-6) in the control and VR groups, respectively (p<0.001). The median (IQR) skin conductance values after colonoscope insertion were 0.660 (0.490-0.840) and 0.390 (0.280-0.600) in the control and VR groups, respectively (p<0.001). Overall, patient satisfaction was significantly improved with the use of VR, along with a significant reduction in the difficulty perceived by the endoscopist. CONCLUSION: VR technology helped to reduce patients' pain and nervousness and to improve patients' satisfaction during colonoscopies.

Radix Rehmannia Glutinosa inhibits the development of renal fibrosis by regulating miR-122-5p/PKM axis.

OBJECTIVE: It is acknowledged that Radix Rehmanniae Praeparata (RR) can regulate hormone metabolism, reduce blood glucose, resist aging, help to sedate patients and promote diuresis. The study aims to investigate the mechanism of how RR influences the development of renal fibrosis by regulating the miR-122-5p/PKM axis. METHODS: Unilateral ureteral obstruction (UUO) was applied to induce renal fibrosis in mice in vivo, and human tubular epithelial HK2 cells treated by transforming growth factor-ß (TGF-ß1) were used to induce renal fibrosis in vitro. Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in mouse serum were detected by Enzyme-linked immunosorbent assay (ELISA); fibronectin (FN) and type I collagen (Col-I) in renal tissue were detected by Western blotting; serum creatinine (Cr) and blood urea nitrogen (BUN) were analyzed by kits. Hematoxylin-eosin (HE) staining and Masson staining were utilized to assess the degree of pathological damage and fibrosis. Cell viability and apoptosis in the in vitro model were detected by MTT and Flow cytometry. Dual-luciferase reporter assay was performed to determine intermolecular targeting relationships. RESULTS: RR could inhibit IL-6 and TNF-α levels, decrease the levels of FN and Col-I and improve the renal function indexes (serum Cr and BUN) in UUO mice (all P<0.05). In addition, RR was able to promote the up-regulation of miR-122-5p expression in UUO mice in vivo (P<0.05). MiR-122-5p expression was down-regulated and PKM expression was up-regulated in HK2 cells treated with TGF-ß1 (all P<0.05). RR inhibited renal fibrosis progression by regulating the miR-122-5p/PKM axis. Inhibition of miR-122-5p or overexpression of PKM could promote apoptosis of TGF-ß1-treated HK2 cells, inhibit their viability, aggravate fibrosis, and attenuate the protective effect of RR on the cells. The protective effect of RR promoted by overexpression of miR-122-5p was partially counteracted by PKM. CONCLUSION: RR can inhibit renal fibrosis progression by regulating the miR-122-5p/PKM axis.

LncRNA FIRRE/NF-kB feedback loop contributes to OGD/R injury of cerebral microglial cells.

Stroke is one of the leading causes for serious long-term neurological disability. LncRNAs have been investigated to be dysregulated in ischemic stroke. However, the underlying mechanisms of some specific lncRNAs have not been clearly clarified. To determine lncRNA-mediated regulatory mechanism in ischemic stroke, we constructed OGD/R injury model of cerebral microglial cells. Microarray analysis was carried out and analyzed that lncRNA functional intergenic repeating RNA element (FIRRE) was associated with OGD/R injury. Based on the molecular biotechnology, we demonstrated that FIRRE could activate NF-kB signal pathway. Meanwhile, the activated NF-kB promoted FIRRE expression in OGD/R-treated cerebral microglial cells. Therefore, FIRRE and NF-kB formed a positive feedback loop to promote the transcription of NLRP3 inflammasome, thus contributed to the OGD/R injury of cerebral microglial cells. All findings in this study may help to explore novel and specific therapeutic target for ischemic stroke.

[Expression of sCD40L in peripheral blood and NF-κBp65 in PBMC of patients with acute progressive cerebral infarction].

AIM: To study the expressional changes of soluble CD40 ligand(sCD40L) in peripheral blood serum and nuclear factor-κB (NF-κB) p65 in peripheral blood mononuclear cells (PBMC) of patients with acute progressive cerebral infarction(APCI). METHODS: We selected ninety-nine patients getting APCI less than 7 d of the onset as APCI group by prospective method. Each 100 cases of patients with acute cerebral infarction(ACI) in the same and with cerebral arteriosclerosis(CAS) in the outpatient were respectively selected as ACI and CAS group. The expressional changes of sCD40L in peripheral blood serum and NF-κBp65 in PBMC of patients with CAS on admission, of patients with APCI and ACI when in hospital, on the course of seventh day, of fourteen and of thirtieth were detected respectively. RESULTS: The expression of sCD40L in peripheral blood serum and NF-κBp65 in PBMC of patients of ACI group on admission were obviously higher all than that of CAS group (P<0.05); The expression of sCD40L in peripheral blood serum and NF-κBp65 in PBMC of patients of APCI group when in hospital, on the course of seventh day, of fourteen and of thirtieth were obviously higher all than that of ACI group (P<0.05 ). CONCLUSION: The inflammatory and apoptotic mechanism mediated by expressional excessive increase of CD40-CD40L signal passage and NF-κB in PBMC might be one of the molecular biology mechanisms of onset and progress for APCI.