This paper analyzed the causes of peripheral nerve injury induced by acupoint injection, and proposed methods for prevention. These methods included emphasizing the physicochemical properties of medications and strengthening research on medication compatibility, classifying high-risk acupoints and establishing international standards for safe acupoint needling, standardizing clinical procedures for acupoint injection, and incorporating ultrasound technology when necessary to improve the accuracy and safety of the procedure. These strategies aimed to reduce the risk associated with the clinical application of acupoint injection.
Humans ; Peripheral Nerve Injuries/prevention & control* ; Ultrasonography ; Acupuncture Points ; Injections/adverse effects*

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

ObjectiveTo systematically explore the underlying mechanisms of Huashi Baidu prescription （HBP） against myocardial injury through a multidimensional network analysis of "transcriptome-putative target-phenotype gene". MethodPutative targets of compounds in HBP were predicted using the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0，http：//www.tcmip.cn/ETCM2/front/） and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0，http：//www.tcmip.cn/TCMIP/index.php/Home/Login/login.html）. Clinical predominant symptom phenotypes for HBP against coronavirus disease 2019 （COVID-19） were collected from CNKI and PubMed databases， while clinical side effects of doxorubicin were gathered from the CTD database. Phenotype-related genes were collected from the HPO database and SoFDA data platform （http：//www.tcmip.cn/Syndrome/front/#/）. An interaction network of "transcriptome-putative target-phenotype gene" was constructed. Key nodes were identified through topological feature calculations， and functional enrichment analysis was conducted to explain the underlying mechanism. Pharmacodynamic evaluation and mechanism verification were performed using a doxorubicin-induced myocardial injury mouse model. Sixty-five SPF-grade C57BL/6J male mice were randomly divided into a control group， a doxorubicin model group， and low-， medium-， and high-dose HBP groups （HBP-L/M/H）， with 13 mice per group. Histopathological severity was assessed using hematoxylin-eosin （HE） and Masson staining. Fibrosis markers were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and protein expression was detected by Western blot. ResultA total of 1 044 putative targets for HBP were obtained from ETCM 2.0 and TCMIP v2.0. From the CTD， HPO， and SoFDA databases， 1 223 potential effect-related targets were identified. Cardiac transcriptome sequencing （RNA-seq） yielded 214 genes related to doxorubicin-induced myocardial injury and 58 genes associated with the effects of HBP， using criteria of P-value<0.05 and FC > 1.5/< 0.667. Analysis of the multidimensional molecular network revealed that the mechanisms of HBP on myocardial injury were mainly related to immune-inflammation imbalance， cellular metabolism， myocardial cell function and fibrosis， angiogenesis， contraction and platelet activation， DNA synthesis， metabolism and repair， as well as cell death and oxidative stress. HBP improved cardiovascular abnormalities such as reduced ejection fraction， myocardial fibrosis， myocarditis， hypertriglyceridemia， and arterial/venous thrombosis. Animal experiments demonstrated that HBP reduced the abnormal high expression of Nod-like receptor heat protein domain Protein 3 （NLRP3）， Caspase-1， apoptosis-associated speck-like protein （ASC）， and Gasdermin D （GSDMD） in myocardial tissue induced by doxorubicin （P<0.05）， and improved the elevated mRNA levels of fibrosis markers transforming growth factor-β₁ （TGF-β₁）， Smad3， and α-smooth muscle actin （α-SMA） （P<0.05）. ConclusionHBP can improve myocardial injury through multiple components， targets， and effects， with the inhibition of the NLRP3 inflammasome activation pathway being a key pharmacodynamic mechanism. This study is expected to provide new insights for the development of targeted therapeutic drugs.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:To observe the effects of ointment and massage on inflammation, oxidative stress and angiogenesis after skeletal muscle trauma, and to explore their mechanisms.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a blank group ( n=6), an ointment and massage (O&M) group ( n=18) and a model group ( n=18). The blunt contusion model of gastrocnemius malformation was established in both the O&M and model groups using self-made percussion instruments. Two hours after successful modeling, the anti-inflammatory pain-relieving cream was applied to the injured area, and massaged evenly and gently for 5 minutes. That was repeated with an interval of 12 hours. No treatment was given to the model and blank groups. On the 1st, 3rd and 7th days after modeling, injured gastrocnemius muscles were resected after collecting abdominal blood. Hematoxylin-eosin (HE) staining and immunofluorescent (CD34) staining were applied, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. Results:HE staining showed that at each time point the gastrocnemius muscle fibers of the model group were significantly more swollen and deformed, collapsed and dissolved than those of the blank group, with a large number of inflamed cells. The O&M group had better recovery, with more newly-generated muscle cells, less inflammatory infiltration and more normal cell shapes than the model group. Fluorescence was stronger in the O&M and model groups than in the blank group at each time point, with that of the O&M group significantly stronger than in the model group. The average SOD and MDA levels in the model and O&M groups were significantly higher than in the blank group, and on the 1st and 3rd days the O&M group′s average SOD level was significantly higher than the model group′s average, though by the 7th day there was no significant difference. The average MDA content of the O&M group was significantly lower than the model group′s average at each time point.Conclusion:Ointment and massage can effectively reduce the local inflammatory response and oxidative stress after a skeletal muscle injury. They can accelerate local angiogenesis, promoting the repair of damaged tissues.

Objective:To investigate the efficacy of different conversion therapies for colorectal cancer with unresectable simultaneous liver metastasis.Methods:A total of 170 patients of colorectal cancer complicated with liver metastasis who were admitted to the First Affiliated Hospital of Nanchang University from Jan 2015 to Dec 2020 were included in the study. Patients were divided into an initial resectable group (42 cases) and an initial non-resectable group (128 cases).Results:There were no significant differences in OS and PFS between patients with CRLM (colorectal cancer with liver metastasis) who were resected initially and those successfully underwent transformation therapy ( P>0.05). The median OS was 36 months in the group with successful transformation, while it was 21 months in the group with simple primary tumor resection and no liver metastasis resection ( P=0.014), HR=0.48 (0.27-0.86). The median PFS was 28 months in the successful conversion group, while it was 10 months in the primary tumor resection only and no liver metastasis resection ( P=0.005), HR=0.43 (0.24-0.77). The OS difference between the group with simple primary tumor resection and no resected liver metastasis and the group with neither primary tumor nor liver metastasis resection was statistically significant: (21 months vs.13 months), HR=0.52 (0.32-0.86) ( P=0.01), while the PFS between the two groups was not statistically significant, ( P>0.05). Conclusions:Chemotherapy combined with targeted therapy has the best effect among the conversion therapies, and can improve the resection rate and survival rate of patients undergoing R 0 surgery. Resection of the primary lesion alone can also prolong the patient's survival.

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

Objective:To investigate the efficacy and safety of precise mechanical thrombectomy based on ABC 2D scale in acute intracranial large artery occlusion stroke (ALVOs). Methods:A prospective study was performed. Two hundred and two patients with ALVOs accepted early mechanical thrombectomy in Department of Neurology, Maoming Clinical School of Guangdong Medical University from January 2021 to February 2022 were enrolled. They were randomly divided into experimental group ( n=102) and control group ( n=100). Stent retriever partially retracted with intermediate catheter for mechanical thrombectomy (SWIM) was the first choice for patients in control group. ABC 2D scale was used to prejudge the pathogenesis of patients in experimental group: patients with scores of 0-3 were considered as having embolic occlusion and a direct aspiration first pass technique (ADAPT) was the first choice, and SWIM would be chosen if suction catheter could not be in place; patients with scores of 4-7 were considered as having intracranial atherosclerotic stenosis occlusion and SWIM was the first choice. The clinical data, surgical effectiveness, surgical safety, and good prognosis rate 90 d after mechanical thrombectomy (modified Rankin scale scores of 0-2 as good prognosis) of the 2 groups were compared. Results:Experimental group had significantly shorter time from puncture to recanalization (51.0[35.0, 78.5] min vs. 67.0[45.0, 100.0] min), and statistically lower NIHSS scores 24 h after mechanical thrombectomy (10.00[4.75, 16.25] vs. 13.00[8.00, 19.00]), significantly higher good prognosis rate 90 d after mechanical thrombectomy (69.6% vs. 46.0%), statistically lower mortality 90 d after mechanical thrombectomy (3.9% vs. 13.0%) compared with control group ( P<0.05). No significant differences were noted in first-pass effect rate, successful vascular revascularization rate, or incidences of symptomatic intracranial hemorrhage (sICH) and ectopic embolization between the control group and experimental group ( P>0.05). Conclusion:Patients with ALVOs accepted early mechanical thrombectomy can have shorter time from puncture to vascular recanalization and better prognosis after etiologically prejudging by ABC 2D scale for thrombectomy.

Objective:To explore the status and influencing factors of stigma in patients with pituitary adenoma.Methods:From January 2020 to May 2021, a total of 106 patients with pituitary adenoma in the Affiliated Huai'an No.1 People 's Hospital of Nanjing Medical University were selected using the convenience sampling method. Internalized Stigma of Mental Illness, Medical Coping Style Questionnaire and Connor-Davidson Resilience Scale were used to investigate them. Binary Logistic regression analysis was used to evaluate the influencing factors of stigma in patients with pituitary adenoma. Results:Among 106 patients with pituitary adenoma, 87 (82.08%) had stigma. The stigma score of patients with pituitary adenoma was (2.58±0.61) . Binary Logistic regression analysis results showed that family monthly income, coping style and mental elasticity were the influencing factors of stigma in patients with pituitary adenoma ( P<0.05) . Conclusions:Stigma is common in patients with pituitary adenoma. Medical staff should take targeted intervention measures according to the influencing factors of stigma in patients with pituitary adenoma, so as to help patients reduce stigma.