CCGIB: A Cross-Channel Graph Information Bottleneck Principle.

The empirical studies of most existing graph neural networks (GNNs) broadly take the original node feature and adjacency relationship as single-channel input, ignoring the rich information of multiple graph channels. To circumvent this issue, the multichannel graph analysis framework has been developed to fuse graph information across channels. How to model and integrate shared (i.e., consistency) and channel-specific (i.e., complementarity) information is a key issue in multichannel graph analysis. In this article, we propose a cross-channel graph information bottleneck (CCGIB) principle to maximize the agreement for common representations and the disagreement for channel-specific representations. Under this principle, we formulate the consistency and complementarity information bottleneck (IB) objectives. To enable optimization, a viable approach involves deriving variational lower bound and variational upper bound (VarUB) of mutual information terms, subsequently focusing on optimizing these variational bounds to find the approximate solutions. However, obtaining the lower bounds of cross-channel mutual information objectives proves challenging through direct utilization of variational approximation, primarily due to the independence of the distributions. To address this challenge, we leverage the inherent property of joint distributions and subsequently derive variational bounds to effectively optimize these information objectives. Extensive experiments on graph benchmark datasets demonstrate the superior effectiveness of the proposed method.

Pregabalin induced balance disorder, asthenia, edema, and constipation in an elderly adult: A case report.

BACKGROUND: Pregabalin is widely used to treat neuropathic pain associated with postherpetic neuralgia. To our knowledge, this is the first report on simultaneously occurring dose-related adverse drug reactions (ADRs) of balance disorder, asthenia, peripheral edema, and constipation in an elderly patient after pregabalin. CASE SUMMARY: A 76-year-old female with a history of postherpetic neuralgia was prescribed pregabalin (300 mg daily). After taking pregabalin for 7 d, the patient developed balance disorder, weakness, peripheral pitting edema (2+), and constipation. On days 8-14, the pregabalin dose was reduced to 150 mg/d based on creatinine clearance. The patient's peripheral edema improved significantly with the disappearance of all other adverse symptoms. On day 15, the pregabalin dose was increased to 225 mg/d to relieve pain. Unfortunately, the symptoms mentioned earlier gradually reappeared after 1 wk of pregabalin treatment. However, the complaints were not as severe as when taking 300 mg/d pregabalin. The patient consulted her pharmacist by telephone and was advised to reduce the dose of pregabalin to 150 mg/d and add acetaminophen (0.5 g, q6h) to relieve pain. The patient's ADRs gradually improved over the following week. CONCLUSION: Older patients should be prescribed a lower initial dose of pregabalin. The dose should be titrated to the maximum tolerable dose to avoid dose-limiting ADR. Dose reduction and the addition of acetaminophen may help limit ADR and improve pain control.

Enhanced recovery after surgery (ERAS) protocol in geriatric patients underwent unicompartmental knee arthroplasty: A retrospective cohort study.

The enhanced recovery after surgery (ERAS) pathway was formulated with the aim to reduce surgical stress response, alleviate pain and guarantee the best-fit experience of patients' perioperative period. However, the application of ERAS in geriatric patients who underwent unicompartmental knee arthroplasty (UKA) was relatively lacking. We hypothesize that UKA patients can benefit from the ERAS protocol. A total of 238 patients were recruited in this retrospective study from August 2018 to December 2021, and Oxford phase III UKA was applied to all patients. ERAS pathway included nutrition support, anesthesia mode, interoperative temperature, and blood pressure control, application of tranexamic acid, early initiation of oral intake and mobilization, and pain management. Demographic data, operation-relative variables, and postoperative complications were analyzed. Forgotten Joint Scores, Oxford Knee Score, Lysholm score, numerical rating scale, and knee range of motion were introduced to estimate the activity function and pain of surgical knee, and these variables were compared between the 2 groups. There were 117 patients in the ERAS group and 121 patients in the traditional group, respectively. The ERAS group had a shorter length of surgical incision and less intraoperative blood loss. Postoperative hemoglobin and albumin of patients in the ERAS group were better than those in the traditional group (P < .05), after 17.0 ± 10.8 months follow-up, the numerical rating scale, Lysholm, Oxford Knee Score, Forgotten Joint Scores, and knee range of motion of patients in the ERAS group were significantly better than the traditional group. The length of hospital stay for patients who underwent ERAS was 11.7 ± 3.8 days and the postoperative complication rate was lower for the ERAS group patients (P = .000 and 0.031). ERAS can reduce the length of hospital stay, and patients can achieve excellent postoperative knee function. The formulation and implementation of the ERAS protocol require good collaboration across multiple disciplines, as well as a deep understanding of the existing clinical evidence and the concept of the ERAS program.

Incidence and risk factors of delayed wound healing in patients who underwent unicompartmental knee arthroplasty.

Unicompartmental knee arthroplasty (UKA) has been proven as an ideal alternative surgical procedure to treat symptomatic isolated knee osteoarthritis, and recently this technique has gained its popularity. However, postoperative complications would inevitably compromise the effectiveness and patients' satisfaction. The objective of this study is to demonstrate the incidence and risk factors of delayed wound healing (DWH) after UKA. This retrospective cohort study was conducted from February 2021 to May 2022 and a total of 211 patients were enrolled. Demographic characteristics, operation-related variables, and laboratory indexes were extracted. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for continuous variables. Univariate and multivariate logistic regression analysis was performed to demonstrate the risk factors of DWH. There were 155 female and 56 male patients with an average age of 64. 6 ± 6.9 years included in this study. After 6.6 ± 4.9 months' follow-up, 12 cases of DWH were observed which indicated an incidence of DWH of 5.7%, mean wound healing duration for 12 patients was 43.1 ± 19.3 days. In the univariate analysis, age > 62.5 years, postoperative hospital stay < 5.5 days, surgical incision < 10.5 cm, barbed suture, body mass index (BMI) > 32.0 kg/m2 , operation duration > 102.5 minutes, intraoperative blood loss > 102.5 mL, preoperative white blood cell count > 5.95*109 /L, preoperative seroglobulin (GLB) > 29.6 g/L, postoperative total protein < 63.4 g/L, postoperative serum albumin < 36.4 g/L, and postoperative GLB > 26.8 g/L were significantly different between patients with and without DWH (P < .05). In final multivariate logistic analysis, results showed that intraoperative blood loss > 102.5 mL (odds ratio [OR], 3.09; P = .001), postoperative hospital stay < 5.5 days (OR, 1.74; P = .014), surgical incision < 10.5 cm (OR, 1.67; P = .000), and BMI > 32.0 kg/m2 (OR, 4.47; P = .022) were independent risk factors for DWH. DWH prolongs hospital stay in UKA patients and increases healthcare expenditure; also affected the implementation schedule of postoperative functional exercise plans. Surgeons should identify patients at risk, meanwhile, make timely and correct clinical interventions to decrease the incidence of this complication.

STAT3-mediated effects of methyltransferase inhibitor 5-aza-2'-deoxycytidine on preeclampsia.

OBJECTIVE: To investigate the effects of 5-aza-2'-deoxycytidine (5-AZA-DC) on preeclampsia (PE) and functional mechanisms dependent on STAT3. MATERIALS AND METHODS: Trophoblastic cells (HTR8/Svneo, JEG-3, JAR and BeWo) were used to constructed STAT3-overexpressing or -silenced cells. qRT-PCR, Western blot, and FISH were used to detect mRNA and protein expression. GST-pull down, ChIP and dual luciferase reporter were used to prove the association of STAT3 and PTEN or TSC2, LC-MS/MS for proteome, and MeDIP-Seq for transcriptome. CCK-8 and flow cytometry were used to examine cell proliferation and apoptosis. C57BL/6J mice were divided into 4 groups (control, control + 5-AZA-DC, PE and PE + 5-AZA-DC). Systolic blood pressure, 24-h urinary protein, APTT, D-D, PT, ALT, Scr, and BUN were determined. Placental blood flow velocity was detected by Doppler ultrasound, HE staining for kidney injury. RESULTS: STAT3, PTEN and TSC2 were the dominantly differential expressed genes in preeclampsia. Aberrant STAT3 expression increased DNMT1 levels. STAT3 regulated PTEN promoter activity. STAT3 interacted with PTEN and TSC2. DNMT1 was increased while STAT3, PTEN and TSC2 were decreased by 5-AZA-DC. Cell proliferation was promoted and apoptosis was inhibited by 5-AZA-DC. PE-induced STAT3 down-regulation was restored by 5-AZA-DC. Systolic blood pressure, 24-h urinary protein, APTT, D-D, PT, ALT, Scr and BUN were increased, and velocity of placental blood flow was inhibited in PE compared with control mice, while 5-AZA-DC relived these indicators. CONCLUSIONS: Preeclampsia symptoms was relieved by 5-AZA-DC, suggesting that 5-AZA-DC could be used as a potential drug for epigenetic treatment of preeclampsia.

Anisotropic Propagation of Chemical Grouting in Fracture Network with Flowing Water.

This paper presents an experimental investigation on the propagation of chemical grouting in a two-dimensional permeated fracture network with various aperture widths. As grouting engineering is often concealed in most experiments, the propagation of grout in fractures is not fully understood. The anisotropic permeability of geological masses with different aperture widths was found and has been investigated since 1960. The deflection flow effect was first found by Tian for groundwater flow in two groups of fractures with different aperture widths. Field grouting indicated that the grout propagates along a group of fractures with larger apertures that are longer while propagating a shorter distance along fractures with small apertures. This phenomenon implies a deflection for grout propagation in fractures with different aperture widths. The results of our study confirm this and indicate that there would be an anisotropy of grout propagation when the two groups of aperture widths are different. The water flow conditions also cause the difference in grout propagation length. When the aperture widths of the two groups of fractures are the same, the propagation shows symmetrical ellipse propagation. The results show the anisotropy of the grout increases as the aperture width ratio increases. This study helps in understanding the mechanism of chemical grouting in fractures with different apertures and flowing water and outlines some implications for grouting design in a fractured rock mass.

Multiobjective Sparse Non-Negative Matrix Factorization.

Non-negative matrix factorization (NMF) is becoming increasingly popular in many research fields due to its particular properties of semantic interpretability and part-based representation. Sparseness constraints are usually imposed on the NMF problems in order to achieve potential features and sparse representation. These constrained NMF problems are usually reformulated as regularization models to solve conveniently. However, the regularization parameters in the regularization model are difficult to tune and the frequently used sparse-inducing terms in the regularization model generally have bias effects on the induced matrix and need an extra restricted isometry property (RIP). This paper proposes a multiobjective sparse NMF paradigm which refrains from the regularization parameter issues, bias effects, and the RIP condition. A novel multiobjective memetic algorithm is also proposed to generate a set of solutions with diverse sparsity and high factorization accuracy. A masked projected gradient local search scheme is specially designed to accelerate the convergence rate. In addition, a priori knowledge is also integrated in the algorithm to reduce the computational time in discovering our interested region in the objective space. The experimental results show that the proposed paradigm has better performance than some regularization algorithms in producing solutions with different degrees of sparsity as well as high factorization accuracy, which are favorable for making the final decisions.

Hydrogen sulfide defends against the cardiovascular risk of Nw-nitro-L-argininemethyl ester-induced hypertension in rats via the nitric oxide/endothelial nitric oxide synthase pathway.

BACKGROUND: Dyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications. Previous studies have shown that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO), and NO/endothelial nitric oxide synthase (eNOS) pathway is the key route of NO production. The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw-nitro-L-argininemethyl ester (L-NAME)-induced hypertensive rats by NO/eNOS pathway. METHODS: Thirty-six 4-week old Sprague-Dawley (SD) male rats were randomly assigned to 6 groups (n = 6): control group, L-NAME group, control + glibenclamide group, control + NaHS group, L-NAME + NaHS group, and L-NAME + NaHS + glibenclamide group. Measurements were made of plasma triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (CHO), glutamic-pyruvic transaminase (ALT) levels after 5 weeks. Then measurements of NO level and proteins expression of eNOS, P-eNOS, AKT, P-AKT were made in liver tissue. RESULTS: After 5 weeks of L-NAME treatment, the blood pressure, plasma TG ((1.22±0.12) mmol/L in L-NAME group vs. (0.68±0.09) mmol/L in control group; P < 0.05) and LDL ((0.54±0.04) mmol/L in L-NAME group vs. (0.28±0.02) mmol/L in control group; P < 0.05) concentration were significantly increased, and the plasma HDL ((0.26±0.02) mmol/L in L-NAME group vs. (0.69±0.07) mmol/L in control group; P < 0.05) concentration significantly decreased. Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS, diminished NO levels ((1.36±0.09) mmol/g protein in L-NAME group vs. (2.34±0.06) mmol/g protein in control group; P < 0.05) and pathological changes of the liver. H2S therapy can markedly decrease the blood pressure ((37.25±4.46) mmHg at the fifth week; P < 0.05), and ameliorate the plasma TG ((0.59±0.06) mmHg), LDL ((0.32±0.04) mmHg), and HDL ((0.46±0.03) mmHg) concentration in L-NAME + NaHS group (all P < 0.05). H2S therapy can also restore eNOS function and NO bioavailability and attenuate the pathological changes in the liver in L-NAME-induced hypertensive rats. CONCLUSION: H2S protects the L-NAME-induced hypertensive rats against liver injury via NO/ eNOS pathway, therefore decreases the cardiovascular risk.

An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain: Role of upregulated neurotrophic factor expression in the hippocampus.

In this study, we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated- resistant mouse 1 strain. Mice from each strain were housed in an enriched environment (including a platform, running wheels, tunnel, and some toys) or a standard environment for 3 months. The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test, and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment. Correspondently, brain-derived neurotrophic factor mRNA and protein expression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment, and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain. These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus.

Involvement of sphingosine 1-phosphate (SIP)/S1P3 signaling in cholestasis-induced liver fibrosis.

Bioactive sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) have been implicated in many critical cellular events, including inflammation, cancer, and angiogenesis. However, the role of S1P/S1PR signaling in the pathogenesis of liver fibrosis has not been well documented. In this study, we found that S1P levels and S1P(3) receptor expression in liver tissue were markedly up-regulated in a mouse model of cholestasis-induced liver fibrosis. In addition, the S1P(3) receptor was also expressed in green fluorescent protein transgenic bone marrow (BM)-derived cells found in the damaged liver of transplanted chimeric mice that underwent bile duct ligation. Silencing of S1P(3) expression significantly inhibited S1P-induced BM cell migration in vitro. Furthermore, a selective S1P(3) receptor antagonist, suramin, markedly reduced the number of BM-derived cells during cholestasis. Interestingly, suramin administration clearly ameliorated bile duct ligation-induced hepatic fibrosis, as demonstrated by attenuated deposition of collagen type I and III, reduced smooth muscle alpha-actin expression, and decreased total hydroxyproline content. In conclusion, our data suggest that S1P/S1P(3) signaling plays an important role in cholestasis-induced liver fibrosis through mediating the homing of BM cells. Modulation of S1PR activity may therefore represent a new antifibrotic strategy.

Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis.

BACKGROUND/AIMS: Myofibroblasts play a central role in the pathogenesis of liver fibrosis. Myofibroblasts of bone marrow (BM) origin have recently been identified in fibrotic liver. However, little is known about the mechanism that controls their mobilization in vivo. Here we confirmed that BM mesenchymal stem cells (BMSCs) can migrate to the damaged liver and differentiate into myofibroblasts. We also investigated the mechanism underlying the homing of BMSCs after liver injury. METHODS: ICR mice were lethally irradiated and received BM transplants from enhanced green fluorescent protein transgenic mice. Carbon tetrachloride or bile duct ligation was used to induce liver fibrosis. The fibrotic liver tissue was examined by immunofluorescent staining to identify BM-derived myofibroblasts. RESULTS: BMSCs contributed significantly to myofibroblast population in fibrotic liver. Moreover, analysis in vivo and in vitro suggested that homing of BMSCs to the damaged liver was in response to sphingosine 1-phosphate (S1P) gradient between liver and BM. Furthermore, S1P receptor type 3 (S1P3) was required for migration of BMSCs triggered by S1P. CONCLUSIONS: S1P mediates liver fibrogenesis through homing of BMSCs via S1P3 receptor, which may represent a novel therapeutic target in liver fibrosis through inhibiting S1P formation and/or receptor activation.