Mechanism of Astragaloside IV in Treatment of Renal Tubulointerstitial Fibrosis.

Tubulointerstitial fibrosis (TIF) is one of the key indicators in evaluating the renal function of patients. Mild TIF can cause a vicious cycle of renal tubular glomerular injury and aggravate renal disease. Therefore, studying the mechanisms underlying TIF is essential to identify therapeutic targets, thereby protecting the renal function of patients with timely intervention. Astragaloside IV (AS-IV) is a Chinese medicine component that has been shown to inhibit the occurrence and progression of TIF via multiple pathways. Previous studies have reported that AS-IV protected against TIF by inhibiting inflammation, autophagy, endoplasmic reticulum stress, macrophages, and transforming growth factor-ß1, which laid the foundation for the development of a new preventive and therapeutic option for TIF.

Electroacupuncture at different intensities inhibits nociceptive discharges of wide dynamic range neurons in spinal dorsal horn of rats. / ä¸åŒå¼ºåº¦ç”µé’ˆå¯¹å¤§é¼ è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒä¼¤å®³æ€§æ”¾ç”µçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level. METHODS: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats. After finding the WDR neuron, electrical stimulation (pulse width of 2 ms) was administered to the plantar receptive field (RF) for determining its response component of discharges according to the latency of action potential generation (Aß ï¼»0 to 20 msï¼½, Aδ ï¼»20 to 90 msï¼½, C ï¼»90 to 500 msï¼½ and post-discharge ï¼»500 to 800 msï¼½). High-intensity electrical stimulation was continuously applied to the RF at the paw's plantar surface to induce DHs neuronal windup response. Subsequently, EA stimulation at different intensities (1 mA and 2 mA) was applied to the left "Zusanli"(ST36) at a frequency of 2 Hz/15 Hz for 10 min. The induction of WDR neuronal windup was then repeated under the same conditions. The quantity of nociceptive discharge components and the windup response of WDR neurons before and after EA stimulations at different intensities were compared. RESULTS: Compared to pre-EA, both EA1 mA and EA2 mA significantly reduced the number of Aδ and C component discharges of WDR neurons during stimulation, as well as post-discharge (P<0.01, P<0.001). The inhibitory rate of C component by EA2 mA was significantly higher than that by EA1 mA (P<0.05). Meanwhile, both EA1 mA and EA2 mA attenuated the windup response of WDR neurons (P<0.05, P<0.01), and the effect of EA2 mA was stronger than that of EA1 mA (P<0.05). Further analysis showed that when EA1 mA and EA2 mA respectively applied to both non-receptive field (non-RF) and RF, a significant reduction in the number of Aδ component, C component and post-discharge was observed (P<0.05, P<0.01). EA2 mA at the non-RF and RF demonstrated a significant inhibitory effect on the windup response of WDR neurons (P<0.01, P<0.05), but EA1 mA only at the non-RF showed a significant inhibitory effect on the windup response (P<0.01). CONCLUSIONS: EA can suppress nociceptive discharges of spinal DHs WDR neurons in rats. The inhibitory impact of EA is strongly correlated with the location and intensity of EA stimulation, and EA2 mA has a stronger inhibitory effect than EA1 mA.

SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1ß pathway.

Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

A combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound in the Kupffer phase for the diagnosis of well-differentiated hepatocellular carcinoma and atypical focal liver lesions: a prospective, multicenter study.

OBJECTIVE: The objective of this study was to develop a combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound (CEUS) during the Kupffer phase and to evaluate its value in differentiating well-differentiated hepatocellular carcinoma (w-HCC) from atypical benign focal liver lesions (FLLs). METHODS: A total of 116 patients with preoperatively Sonazoid-CEUS confirmed w-HCC or benign FLL were selected from a prospective multiple study on the clinical application of Sonazoid in FLLs conducted from August 2020 to March 2021. According to the randomization principle, the patients were divided into a training cohort and a test cohort in a 7:3 ratio. Seventy-nine patients were used for establishing and training the radiomics model and combined model. In comparison, 37 patients were used for validating and comparing the performance of the models. The diagnostic efficacy of the models for w-HCC and atypical benign FLLs was evaluated using ROCs curves and decision curves. A combined model nomogram was created to assess its value in reducing unnecessary biopsies. RESULTS: Among the patients, there were 55 cases of w-HCC and 61 cases of atypical benign FLLs, including 28 cases of early liver abscess, 16 cases of atypical hepatic hemangioma, 8 cases of hepatocellular dysplastic nodules (DN), and 9 cases of focal nodular hyperplasia (FNH). The radiomics model and combined model we established had AUCs of 0.905 and 0.951, respectively, in the training cohort, and the AUCs of the two models in the test cohort were 0.826 and 0.912, respectively. The combined model outperformed the radiomics feature model significantly. Decision curve analysis demonstrated that the combined model achieved a higher net benefit within a specific threshold probability range (0.25 to 1.00). A nomogram of the combined model was developed. CONCLUSION: The combined model based on the radiomics features of Sonazoid-CEUS in the Kupffer phase showed satisfactory performance in diagnosing w-HCC and atypical benign FLLs. It can assist clinicians in timely detecting malignant FLLs and reducing unnecessary biopsies for benign diseases.

The comparison of contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI LI-RADS for nodules ≤2 cm in patients at high risk for HCC: a prospective study.

Objectives: To investigate the consistency of LI-RADS of CEUS and EOB-MRI in the categorization of liver nodules ≤2cm in patients at high risk for HCC. Methods: Patients at high risk for HCC with nodules ≤2cm who underwent CEUS and EOB-MRI in our hospital were prospectively enrolled. The CEUS images and EOB-MRI imaging of each liver nodule were observed to evaluate inter-observer consistency and category according to CEUS LI-RADS V2017 and CT/MRI LI-RADS V2017 criteria double blinded. Pathology and/or follow-up were used as reference standard. Results: A total of 127 nodules in 119 patients met the inclusion criteria. The inter-observer agreement was good on CEUS and EOB-MRI LI-RADS (kappa = 0.76, 0.76 p < 0.001). The inter-modality agreement was fair (kappa=0.21, p < 0.001). There was no statistical difference in PPV and specificity between CEUS and EOB-MRI LR-5 for HCC, while the difference in AUC was statistically significant. We used new criteria (CEUS LR-5 and EOB-MRI LR-4/5 or CEUS LR-4/5 and EOB-MRI LR-5) to diagnose HCC. The sensitivity, specificity, and AUC of this criteria was 63.4%, 95.6%, and 0.80. Conclusions: CEUS and EOB-MRI showed fair inter-modality agreement in LI-RADS categorization of nodules ≤2 cm. The inter-observer agreement of CEUS and EOB-MRI LI-RADS were substantial. CEUS and EOB-MRI LR-5 have equally good positive predictive value and specificity for HCC ≤ 2cm, and combining these two modalities may better diagnose HCC ≤ 2 cm. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04212286.

Preliminary study on diagnosis of gallbladder neoplastic polyps based on contrast-enhanced ultrasound and grey scale ultrasound radiomics.

Objective: Neoplastic gallbladder polyps (GPs), including adenomas and adenocarcinomas, are considered absolute indications for surgery; however, the distinction of neoplastic from non-neoplastic GPs on imaging is often challenging. This study thereby aimed to develop a CEUS radiomics nomogram, and evaluate the role of a combined grey-scale ultrasound and CEUS model for the prediction and diagnosis of neoplastic GPs. Methods: Patients with GPs of ≥ 1 cm who underwent CEUS between January 2017 and May 2022 were retrospectively enrolled. Grey-scale ultrasound and arterial phase CEUS images of the largest section of the GPs were used for radiomics feature extraction. Features with good reproducibility in terms of intraclass correlation coefficient were selected. Grey-scale ultrasound and CEUS Rad-score models were first constructed using the Mann-Whitney U and LASSO regression test, and were subsequently included in the multivariable logistic regression analysis as independent factors for construction of the combined model. Results: A total of 229 patients were included in our study. Among them, 118 cholesterol polyps, 68 adenomas, 33 adenocarcinomas, 6 adenomyomatoses, and 4 inflammatory polyps were recorded. A total of 851 features were extracted from each patient. Following screening, 21 and 15 features were retained in the grey-scale and CEUS models, respectively. The combined model demonstrated AUCs of 0.88 (95% CI: 0.83 - 0.93) and 0.84 (95% CI: 0.74 - 0.93) in the training and testing set, respectively. When applied to the whole dataset, the combined model detected 111 of the 128 non-neoplastic GPs, decreasing the resection rate of non-neoplastic GPs to 13.3%. Conclusion: Our proposed combined model based on grey-scale ultrasound and CEUS radiomics features carries the potential as a non-invasive, radiation-free, and reproducible tool for the prediction and identification of neoplastic GPs. Our model may not only guide the treatment selection for GPs, but may also reduce the surgical burden of such patients.

Effectivity and safety of trifocal intraocular lenses and capsular tension rings implantation for cataract patients with axial high myopia.

AIM: To assess effectivity and safety of trifocal intraocular lenses (IOLs) and capsular tension rings in treating cataract patients with axial high myopia. METHODS: A prospective nonrandomized controlled clinical trial was conducted. Totally 98 eyes (74 patients) who underwent femtosecond laser-assisted cataract surgery (FLACS) with trifocal IOLs were enrolled in the study and followed up for 2y after surgery: 46 eyes (33 patients) with capsular tension ring implantation in the long axial lengths (AL) group (260.05). The dysfunctional lens index and total modulation transfer function (MTF) average height were similar between the two groups. The postoperative internal coma aberrations in the axial high myopia eyes were significantly higher than that in the normal AL group (P<0.05). The total satisfaction score in the long AL group (91.32±2.76) was slightly higher than that in the normal AL group (90.36±3.47), but there was no difference (P=0.136). A statistically negative correlation was found between corrected distance visual acuity (CDVA) and dysfunctional lens index (r=-0.382, P=0.009), and between CDVA and the total MTF average height (r=-0.374, P=0.01). But there was no significant correlation between CDVA and total satisfaction score (r=0.059, P=0.696). Postoperative complications mainly presented as posterior capsular opacity (PCO), retinal detachment and cystoid macular edema. There was no difference in the incidence of fundus disease (6.5% vs 3.8%, P=0.663) or PCO (17.4% vs 7.7%, P=0.217) between the two groups at two years. CONCLUSION: The utilization of trifocal IOL and capsular tension ring implantation is beneficial for cataract patients with axial high myopia undergoing FLACS. This approach not only ensures excellent subjective feelings and objective visual quality, but also does not increase the incidence of postoperative complications.

Head-to-head comparison of three different US-based quantitative parameters for hepatic steatosis assessment: a prospective study.

PURPOSE: To evaluate the diagnostic performance of attenuation coefficient (AC), hepato-renal index (HRI) and controlled attenuation parameter (CAP) in quantitative assessment of hepatic steatosis by employing histopathology as reference standard. METHODS: Participants with suspected metabolic-associated fatty liver disease (MAFLD) who underwent US-based parameter examinations and liver biopsy were prospectively recruited. The distributions of US parameters across different grades of steatosis were calculated, and diagnostic performance was determined based on the areas under the receiver operating characteristic curve (AUC). RESULTS: A total of 73 participants were included, with hepatic steatosis grades S0, S1, S2, and S3 distributed as follows: 13, 20, 27, and 13 respectively. The correlation coefficients for CAP, AC, and HRI ranged from 0.67 to 0.74. AC and HRI showed a strong correlation with steatosis grade. The AUC for CAP and AC in diagnosing steatosis ≥ S1 were significantly higher at 0.99 and 0.98 compared to HRI's value. For diagnosing steatosis ≥ S2, the AUC of CAP (AUC: 0.85) was lower than that of AC (AUC: 0.94), and HRI (AUC: 0.94). Similarly for diagnosing steatosis S3, the AUC of CAP (AUC: 0.68) was lower than that of AC (AUC: 0.88), and HRI (AUC: 0.88). CONCLUSION: The AC and HRI values increased with the progression of hepatic steatosis grade, while CAP increased from S0 to S2 but not from S2 to S3. For mild steatosis diagnosis, CAP and AC showed superior diagnostic performance compared to HRI, while AC and HRI were more advantageous in differentiating moderate and severe steatosis.

Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury.

AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma. METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina. CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

Dynamic Contrast-Enhanced Ultrasonography Combined With LR-M Classification Criteria for Differentiating Malignant Liver Nodules at High Risk for Hepatocellular Carcinoma.

OBJECTIVE: We aimed to investigate the value of quantitative parameters derived from dynamic contrast-enhanced ultrasonography (DCE-US) and a combination of these quantitative parameters with the LR-M classification criteria in distinguishing hepatocellular carcinoma (HCC) nodules and non-HCC malignancies. METHODS: HCC and non-HCC malignant nodules were grouped using pathologic results, and each nodule was classified using CEUS LI-RADS 2017. Quantitative CEUS analysis of each nodule was performed using VueBox, and quantitative parameters were compared between the HCC and non-HCC groups. The diagnostic efficacy of the LR-5 category for HCC was analyzed using the LR-M classification criteria along with time-related quantitative parameters. RESULTS: Of the 190 malignant liver nodules, 137 and 53 were HCCs and non-HCC malignancies, respectively. The median values of quantitative parameters RT (rise time), TTP (time to peak), mTTl (mean transit time local), and FT (fall time) in the non-HCC malignant group were lower than those in the HCC group, with p < 0.05. There was a statistically significant difference in WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve), and WoR (wash-out rate) values between HCC and non-HCC malignant groups, with p < 0.05. Using LR-M washout time <60 s and FT ≤21.2 s as the new diagnostic standard, the LR-5 category showed a sensitivity of 83.9%, specificity of 96.2%, and positive predictive value of 98.3% for HCC diagnosis. CONCLUSION: DCE-US can facilitate the distinction of HCCs and non-HCC malignancies. Non-HCC malignancies present with earlier peak enhancement and more rapid and marked washout than HCC nodules. The combination of the LR-M classification criteria and FT ≤21.2 s can significantly improve the diagnostic sensitivity of the LR-5 category for HCC.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

BACKGROUND: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition. METHODS: Here, we leveraged 2 models of in vitro cultured adult mouse cardiomyocytes and in vivo adeno-associated virus serotype 9 cardiomyocyte-targeted delivery of reprogramming factors (Oct4, Sox2, Klf4, and Myc) in adult mice to study CMDD. We profiled their transcriptomes using RNA sequencing, in combination with multiple published data sets, with the aim of identifying a common denominator for tracking CMDD. RESULTS: RNA sequencing and integrated analysis identified Asparagine Synthetase (Asns) as a unique molecular marker gene well correlated with CMDD, required for increased asparagine and also for distinct fluxes in other amino acids. Although Asns overexpression in Oct4, Sox2, Klf4, and Myc cardiomyocytes augmented hallmarks of CMDD, Asns deficiency led to defective regeneration in the neonatal mouse myocardial infarction model, increased cell death of cultured adult cardiomyocytes, and reduced cell cycle in Oct4, Sox2, Klf4, and Myc cardiomyocytes, at least in part through disrupting the mammalian target of rapamycin complex 1 pathway. CONCLUSIONS: We discovered a novel gene Asns as both a molecular marker and an essential mediator, marking a distinct threshold that appears in common for at least 4 models of CMDD, and revealing an Asns/mammalian target of rapamycin complex 1 axis dependency for dedifferentiating cardiomyocytes. Further study will be needed to extrapolate and assess its relevance to other cell state transitions as well as in heart regeneration.

Malignancy diagnosis of liver lesion in contrast enhanced ultrasound using an end-to-end method based on deep learning.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered as an efficient tool for focal liver lesion characterization, given it allows real-time scanning and provides dynamic tissue perfusion information. An accurate diagnosis of liver lesions with CEUS requires a precise interpretation of CEUS images. However,it is a highly experience dependent task which requires amount of training and practice. To help improve the constrains, this study aims to develop an end-to-end method based on deep learning to make malignancy diagnosis of liver lesions using CEUS. METHODS: A total of 420 focal liver lesions with 136 benign cases and 284 malignant cases were included. A deep learning model based on a two-dimensional convolution neural network, a long short-term memory (LSTM), and a linear classifier (with sigmoid) was developed to analyze the CEUS loops from different contrast imaging phases. For comparison, a 3D-CNN based method and a machine-learning (ML)-based time-intensity curve (TIC) method were also implemented for performance evaluation. RESULTS: Results of the 4-fold validation demonstrate that the mean AUC is 0.91, 0.88, and 0.78 for the proposed method, the 3D-CNN based method, and the ML-based TIC method, respectively. CONCLUSIONS: The proposed CNN-LSTM method is promising in making malignancy diagnosis of liver lesions in CEUS without any additional manual features selection.

Multiparametric US for Identifying Metabolic Dysfunction-associated Steatohepatitis: A Prospective Multicenter Study.

Background Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China. Multivariable logistic regression was performed to assess risk factors associated with MASH. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate diagnostic performance in predicting MASH in training and validation groups (6:4 ratio of participants), and for a post hoc subgroup analysis of hepatitis B virus infection and diabetes. Results A total of 424 participants (median age, 47 years; IQR, 34-59 years; 244 male) were evaluated, including 332 participants (78%) with MASH and 92 (22%) without. Attenuation coefficient (AC) (odds ratio [OR], 3.32 [95% CI: 1.94, 5.71]; P < .001), alanine aminotransferase (ALT) level (OR, 4.42 [95% CI: 1.78, 10.94]; P = .001), and international normalized ratio (INR) (OR, 0.59 [95% CI: 0.37, 0.95]; P = .03) were independently associated with MASH. A combined model (AC, ALT, and INR) had AUCs of 0.85 (95% CI: 0.79, 0.91) and 0.77 (95% CI: 0.69, 0.85) for predicting MASH in the training and validation groups, respectively. AUC values for the subgroups with and without diabetes were 0.83 (95% CI: 0.72, 0.94) and 0.81 (95% CI: 0.75, 0.87) and for the subgroups with and without hepatitis B were 0.82 (95% CI: 0.74, 0.90) and 0.79 (95% CI: 0.71, 0.87), respectively. Conclusion A model combining AC, ALT level, and INR showed good discrimination ability for predicting MASH in participants with MAFLD. Clinical trial registration no. NCT04551716 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Reuter in this issue.

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Ligand-Controlled Cobalt-Catalyzed Regio-, Enantio-, and Diastereoselective Oxyheterocyclic Alkene Hydroalkylation.

Metal-hydride-catalyzed alkene hydroalkylation has been developed as an efficient method for C(sp3)-C(sp3) coupling with broad substrate availability and high functional group compatibility. However, auxiliary groups, a conjugated group or a chelation-directing group, are commonly required to attain high regio- and enantioselectivities. Herein, we reported a ligand-controlled cobalt-hydride-catalyzed regio-, enantio-, and diastereoselective oxyheterocyclic alkene hydroalkylation without chelation-directing groups. This reaction enables the hydroalkylation of conjugated and unconjugated oxyheterocyclic alkenes to deliver C2- or C3-alkylated tetrahydrofuran or tetrahydropyran in uniformly good yields and with high regio- and enantioselectivities. In addition, hydroalkylation of C2-substituted 2,5-dihydrofuran resulted in the simultaneous construction of 1,3-distereocenters, providing convenient access to polysubstituted tetrahydrofuran with multiple enantioenriched C(sp3) centers.

Promoting high-quality development of acupuncture and moxibustion. / 推进针灸学科的高质量发展.

In the past 20 years, the acupuncture-moxibustion discipline has made a great progress in clinical research, method construction, standard formulation, guideline promotion, basic theory and key scientific issue research. Internationally, the development of acupuncture and moxibustion has gradually begun to pay more attention to the basic issues of the discipline itself from focusing on clinical evidence. The National Institute of Health of USA pays close attention to the construction of acupoint knowledge base and database and to the transformation of peripheral nerve stimulation techniques, which brings forth opportunities and challenges for the development of acupuncture-moxibustion discipline. In the present paper, we analyze the shortcomings of the current development of acupuncture and moxibustion, put forward some strategies for high-quality development in the future, and sort out the basic scientific issues to form an academic consensus. We should employ modern scientific language to express the scientific connotations of the basic theory of acupuncture and moxibustion, and build an open and self-consistent modern theoretical system. In addition, we also should attract more multidisciplinary talents to harmoniously and assiduously work together, insist on continuous innovation to open up a new situation in the transformation of basic scientific research achievements, and establish a new theoretical system of "somato-medicine" represented by acupuncture and moxibustion. In this way, we will guide the acupuncture-moxibustion discipline to make an original contribution to the modern life science and future medicine.

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Functional analysis of Ornithine decarboxylase in manipulating the wing dimorphism in Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

The brown planthopper (BPH, Nilaparvata lugens), a major insect pest of rice, can make a shift in wing dimorphism to adapt to complex external environments. Our previous study showed that NlODC (Ornithine decarboxylase in N. lugens) was involved in wing dimorphism of the brown planthopper. Here, further experiments were conducted to reveal possible molecular mechanism of NlODC in manipulating the wing dimorphism. We found that the long-winged rate (LWR) of BPH was significantly reduced after RNAi of NlODC or injection of DFMO (D, L-α-Difluoromethylornithine), and LWR of males and females significantly decreased by 21.7% and 34.6%, respectively. Meanwhile, we also examined the contents of three polyamines under DFMO treatment and found that the contents of putrescine and spermidine were significantly lower compared to the control. After 3rd instar nymphs were injected with putrescine and spermidine, LWR was increased significantly in both cases, and putrescine was a little bit more effective, with 5.6% increase in males and 11.4% in females. Three days after injection of dsNlODC, injection of putrescine and spermidine rescued LWR to the normal levels. In the regulation of wing differentiation in BPH, NlODC mutually antagonistic to NlAkt may act through other signaling pathways rather than the classical insulin signaling pathway. This study illuminated a physiological function of an ODC gene involved in wing differentiation in insects, which could be a potential target for pest control.

Effects of hydroxy methionine zinc on growth performance, immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii).

This study aimed to evaluate the effects of varying zinc (Zn) levels on the growth performance, non-specific immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii (P. clarkii)). Adopting hydroxy methionine zinc (Zn-MHA) as the Zn source, 180 healthy crayfish with an initial body mass of 6.50 ± 0.05 g were randomly divided into the following five groups: X1 (control group) and groups X2, X3, X4, and X5, which were fed the basal feed supplemented with Zn-MHA with 0, 15, 30, 60, and 90 mg kg-1, respectively. The results indicated that following the addition of various concentrations of Zn-MHA to the diet, the following was observed: Specific growth rate (SGR), weight gain rate (WGR), total protein (TP), total cholesterol (TC), the activities of alkaline phosphatase (AKP), phenoloxidase (PO), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT), the expression of CTL, GPX, and CuZn-SOD genes demonstrated a trend of rising and then declining-with a maximum value in group X4-which was significantly higher than that in group X1 (P < 0.05). Zn deposition in the intestine and hepatopancreas, the activity of GSH-PX, and the expression of GSH-PX were increased, exhibiting the highest value in group X5. The malonaldehyde (MDA) content was significantly reduced, with the lowest value in group X4, and the MDA content of the Zn-MHA addition groups were significantly lower than the control group (P < 0.05). In the analysis of the intestinal microbiota of P. clarkii, the number of operational taxonomic units in group X4 was the highest, and the richness and diversity indexes of groups X3 and X4 were significantly higher than those in group X1 (P < 0.05). Meanwhile, the dietary addition of Zn-MHA decreased and increased the relative abundance of Proteobacteria and Tenericutes, respectively. These findings indicate that supplementation of dietary Zn-MHA at an optimum dose of 60 mg kg-1 may effectively improve growth performance, immune response, antioxidant capacity, and intestinal microbiota richness and species diversity in crayfish.