Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

Primary animal experiment to test the feasibility of a novel Y-Z magnetic hepatic portal blocking band.

BACKGROUND: Hepatic portal blood flow occlusion is a common technique for reducing hepatic hemorrhage during hepatectomy. We designed a novel Y-Z magnetic hepatic portal blocking band (Y-Z MHPBB) based on the principle of magnetic compression technique. AIM: To introduce the Y-Z MHPBB device and verify the feasibility of this device for hepatic portal blood flow occlusion in dogs. METHODS: Ten beagles were randomly divided into the experimental group and control group. The operation time, intraoperative blood loss, the number of portal blood flow occlusions, the total time spent on adjusting the blocking band, and the average time spent on adjusting the blocking band were recorded. The surgeons evaluated the feasibility and flexibility of the two portal occlusion devices. RESULTS: Laparoscopic hepatectomy was successfully performed in both the experimental group and control group. There was no statistical difference between the two groups in the operation time, intraoperative blood loss, and the number of hepatic portal blood flow occlusions. With respect to the total time spent on adjusting the blocking band and the average time spent on adjusting the blocking band, the experimental group showed significantly better outcomes than the control group, with a statistical difference (P < 0.05). The operators found that the Y-Z MHPBB was superior to the modified T-tube in terms of operational flexibility. CONCLUSION: The Y-Z MHPBB seems to be an ingenious design, accurate blood flow occlusion effect, and good flexibility; and it can be used for hepatic portal blood flow occlusion during laparoscopic hepatectomy.

Magnetic compression anastomosis for reconstruction of digestive tract after total gastrectomy in beagle model.

BACKGROUND: Magnetic compression anastomosis (MCA) is a simple procedure contributing to a reliable anastomosis. However, digestive-tract reconstruction after total gastrectomy using MCA has not yet been reported. AIM: To investigate the feasibility of MCA for simultaneous esophagojejunostomy and jejunojejunostomy after total gastrectomy using beagle dogs. METHODS: Sixteen beagles were randomly divided into an MCA group (study group, n = 8) and a manual-suture anastomosis group (control group, n = 8). Two different magnetic anastomosis devices were used in the study group for esophagojejunal and jejunojejunal anastomoses. Both devices included a pair of circular daughter and parent magnets each. The time of esophagojejunostomy and jejunojejunostomy, postoperative complications, and survival rate of the two groups were compared. The dogs were sacrificed one month after the operation and their anastomotic specimens were obtained. Healing was observed by the naked eye and a light microscope. RESULTS: Digestive-tract reconstruction after total gastrectomy was successfully completed in both groups (survival rate = 100%). In the study group, esophagojejunal and jejunojejunal anastomoses took 6.13 ± 0.58 and 4.06 ± 0.42 min, respectively, significantly lower than those in the control group (15.63 ± 1.53 min, P < 0.001 and 10.31 ± 1.07 min, P < 0.001, respectively). Complications such as bleeding, anastomotic leakage, and anastomotic stenosis were not observed. In the study group, the magnets did not interfere with each other. Discharge time of the jejunojejunal magnetic anastomosis device was 10.75 ± 1.28 d, while that of the esophagojejunal magnetic anastomosis device was 12.25 ± 1.49 d. Residual silk was found in the control group. The study group showed a greater smoothness of the anastomosis than that of the control group. All layers of anastomosis healed well in both groups. CONCLUSION: MCA is a safe and feasible procedure for digestive-tract reconstruction after total gastrectomy in this animal model.

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

All-Trans Retinoic Acid Promotes M2 Macrophage Polarization in Vitro by Activating the p38MAPK/STAT6 Signaling Pathway.

BACKGROUND: M2-type macrophages are inflammation-suppressing cells that are differentiated after induction by cytokines such as IL-4 or IL-13, which play an important regulatory role in inflammation and influence the regression of inflammation-related diseases. All-trans retinoic acid (ATRA) has an important role in suppressing immune-mediated inflammatory responses but the effect and underlying mechanism of ATRA on the polarization of M2 macrophages remains unclear. METHODS: Macrophages were isolated from peritoneal wash fluid, and IL-4 (20 ng/mL) was used to construct a m2-type macrophage polarization model. The model was incubated with different concentrations of ATRA (15 µg/ml, 30 µg/ml, 45 µg/ml) for 24 h, and pretreated macrophages with p38MAPKα inhibitor SB202190 (20 µM). MTT, Trypan blue staining, Annexin V-PE/7-AAD staining, flow cytometry, real-time PCR and western blotting were used to investigate the effect and mechanism of ATRA on the polarization of M2 macrophages. RESULTS: Compared with the IL-4 group, the proportion of F4/80+CD206+ M2-type macrophages was significantly higher in the ATRA group (P < 0.01). mRNA and protein expression levels of Arg-1, IL-10 and TGF-ß1 were as significantly higher (P < 0.01) in the ATRA group as phosphorylation levels of STAT6 and p38MAPK (P < 0.01). After pretreatment with the addition of the inhibitor SB202190, M2-type macrophages proportion and their associated factors expression were significantly (P < 0.01) reduced, as compared with those in the ATRA group, but they were comparable (P > 0.05) with the IL-4 group. CONCLUSION: The combination of ATRA and IL-4 activated the p38MAPK/STAT6-signaling pathway to promote polarization of M2 macrophages.

Motor-sparing peripatellar plexus block provides noninferior block duration and complete block area of the peripatellar region compared with femoral nerve block: a randomized, controlled, noninferiority study.

BACKGROUND: Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers. METHODS: The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded. RESULTS: The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was - 1.24 (95% CI, -2.81 - 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (Pnoninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block. CONCLUSION: Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020).

Pazopanib restricts small cell lung cancer proliferation via reactive oxygen species-mediated endoplasmic reticulum stress.

BACKGROUND: Pazopanib is an approved multitarget anticancer agent for soft tissue sarcoma (STS) and renal cell carcinoma (RCC), which is also under clinical investigation for other malignancies, including small cell lung cancer (SCLC). However, the potential anti-SCLC mechanisms of pazopanib remain unclear. METHODS: Cell viability was evaluated by CCK-8, apoptotic cell detection was conducted using annexin V/PI staining followed by flow cytometry, and Western blot analysis was used to detect the apoptotic-related molecules and ER-stress pathway effectors. The intracellular reactive oxygen species (ROS) level was determined by DCFH-HA staining followed by flow cytometry. An NCI-H446 xenograft model was established to evaluate pazopanib on tumor suppression in vivo. Immunohistochemistry (IHC) was used to assess the proliferative activity of xenograft in NCI-H446 cell-bearing NOD-SCID mice. RESULTS: Pazopanib dose- and time-dependently inhibited SCLC cell proliferation induced significant apoptosis in SCLC cell lines, increased cleaved-caspase3 and Bax, and decreased Bcl-2. Moreover, the PERK-related ER-stress pathway was potently activated by pazopanib treatment, inhibiting ER-stress by salubrinal significantly reversing pazopanib-mediated apoptosis in SCLC cell lines. Furthermore, pazopanib-induced intracellular ROS levels increased, while inhibiting ROS by NAC significantly reversed pazopanib-induced apoptosis in SCLC cells. In addition, pazopanib significantly suppressed NCI-H446 xenograft growth and decreased Ki67 positive cells in the tumor. CONCLUSION: Our findings indicate that pazopanib induces SCLC cell apoptosis through the ER-stress process via upregulation of ROS levels. Further investigation of relevant biomarkers to accurately select patients for benefit from pazopanib should be further investigated.

Plasma CXCL14 as a Candidate Biomarker for the Diagnosis of Lung Cancer.

Background: Effective biomarkers for early diagnosis of lung cancer are needed. Previous studies have indicated positive associations between abnormal circulating cytokines and the etiology of lung cancer. Methods: Blood samples were obtained from 286 patients with pretreatment lung cancer and 80 healthy volunteers. Circulating cytokine levels were detected with a Luminex assay and enzyme-linked immunosorbent assay (ELISA). Urine samples were obtained from 284 patients and 122 healthy volunteers. CXC chemokine ligand 14 (CXCL14) expression in tumors and nontumor regions of lung tissues from 133 lung cancer cases was detected by immunohistochemical (IHC) staining and immunofluorescence (IF) staining of formalin fixed paraffin-embedded (FFPE) tissues. Results: Compared with healthy volunteers, a 65.7-fold increase was observed in the level of CXCL14 in the plasma of lung cancer patients, and a 1.7-fold increase was observed in the level of CXCL14 in the urine of lung cancer patients, achieving a 0.9464 AUC (area under the curve) value and a 0.6476 AUC value for differentiating between lung cancer patients and healthy volunteers, respectively. Stromal CXCL14 expression was significantly associated with advanced pathologic stage (P<0.001), pathologic N stage (P<0.001), and recurrence and metastasis (P=0.014). Moreover, multivariate analysis suggested stromal CXCL14 expression as an independent predictor of DFS and OS. Conclusions: Our study demonstrates that CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer. Impact: CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.

Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.

Electrochemical Trifluoromethylation of Thiophenols with Sodium Trifluoromethanesulfinate.

We developed an electrochemical trifluoromethylation of thiophenols without the use of metal catalysts and oxidants. This reaction features mild reaction conditions, readily available substrate, as well as moderate to good yields. In addition, this protocol can be easily scaled up with moderate efficiency.

Circulating Serum Myonectin Levels in Obesity and Type 2 Diabetes Mellitus.

OBJECTIVE: Myonectin is one of the myokines and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM).The objective of this study was to investigate circulating serum myonectin levels in nondiabetes and T2DM and elucidate possible relationships between serum myonectin levels and metabolic parameters in patients with T2DM. DESIGN: A total of 362 Chinese patients with T2DM and 100 age- and sex-matched healthy controls were recruited in this study. Clinical characteristics, blood biochemistry, and circulating myonectin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating myonectin levels were significantly decreased in T2DM compared with controls. Obese nondiabetic controls had significantly lower serum myonectin levels compared with lean nondiabetic controls. In diabetic patients, serum myonectin concentrations were significantly negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), hemoglobin A1c (HbA1c), fasting insulin (Fins), the homeostatic model assessment of insulin resistance (HOMA-IR), visceral fat area, and subcutaneous fat area. After adjusting for covariates, multivariate stepwise regression analysis demonstrated that BMI, LDL-C, TG, HOMA-IR, and visceral fat were the main independent predictors of low serum myonectin concentrations. CONCLUSIONS: Circulating myonectin levels were decreased in T2DM patients and in obese subjects. Moreover, serum myonectin levels were correlated with metabolic markers of T2DM. These data suggest that myonectin may be a useful marker in predicting the development of obesity and T2DM.

Prenatal maternal stress and autistic-like behaviours in Chinese preschoolers.

Exposure to prenatal maternal stress (PNMS) has been implicated as a risk factor for a range of psychiatric disorders in children. However, there have been a few studies showing inconsistent associations between PNMS and offspring autistic-like behaviours. We therefore aimed to examine whether trimester-specific PNMS exposure might be related to an increased risk of autistic-like behaviours among preschoolers. Using data from Longhua Children Cohort Study, mothers of 65,931 preschool children were asked to recall their level of PNMS in each of the three trimesters of pregnancy, while children's current autistic-like behaviours were assessed using the Autism Behaviour Checklist. A series of Cox regression models were fitted to assess the association between PNMS exposure and autistic-like behaviours. After adjusting for potential confounders, the Cox regression models showed that PNMS exposure, especially during the second pregnant trimester, was significantly and positively associated with the presence of children's autistic-like behaviours. The strength of these associations was enhanced with the increase of PNMS exposure level. Furthermore, based on different permutations of exposure versus no exposure in each trimester, the participants were divided into eight groups. A cross-over analysis confirmed the aforementioned finding that the second pregnant trimester might be the sensitive period for PNMS exposure increasing the risk of autistic-like behaviours. Our findings supported the hypothesis of an association between PNMS exposure and autistic-like behaviours among preschoolers. Preventive interventions should be trialled to examine whether minimizing maternal psychological stress during pregnancy, especially the second trimester, may reduce the risk of offspring autistic-like behaviours.