Gut-targeted therapies for type 2 diabetes mellitus: A review.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. The global prevalence of T2DM has reached epidemic proportions, affecting approximately 463 million adults worldwide in 2019. Current treatments for T2DM include lifestyle modifications, oral antidiabetic agents, and insulin therapy. However, these therapies may carry side effects and fail to achieve optimal glycemic control in some patients. Therefore, there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM. The gut microbiota, which refers to the community of microorganisms that inhabit the human gut, has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity. Alterations in gut microbiota composition and diversity have been observed in T2DM patients, with a reduction in beneficial bacteria and an increase in pathogenic bacteria. This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function. Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM. One potential approach is the use of probiotics, which are live microorganisms that confer health benefits to the host when administered in adequate amounts. Several randomized controlled trials have demonstrated that certain probiotics, such as Lactobacillus and Bifidobacterium species, can improve glycemic control and insulin sensitivity in T2DM patients. Mechanisms may include the production of short-chain fatty acids, the improvement of gut barrier function, and the reduction of inflammation. Another gut-targeted therapy is fecal microbiota transplantation (FMT), which involves the transfer of fecal material from a healthy donor to a recipient. FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM. A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity. However, FMT carries potential risks, including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable. In addition to probiotics and FMT, other gut-targeted therapies are being investigated for the management of T2DM, such as prebiotics, synbiotics, and postbiotics. Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria, while synbiotics combine probiotics and prebiotics. Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host. The NIH SPARC program, or the Stimulating Peripheral Activity to Relieve Conditions, is a research initiative aimed at developing new therapies for a variety of health conditions, including T2DM. The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs, in order to regulate glucose levels in the body. The goal of this approach is to develop targeted, non-invasive therapies that can help patients better manage their diabetes. One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve, which plays an important role in regulating glucose metabolism. Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM. Gut-targeted therapies, such as probiotics and FMT, have shown potential for improving glycemic control and insulin sensitivity in T2DM patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies.

[Feasibility analysis of puncture robot technology for the application of acupuncture robot].

The difficulties such as how to accurately locate acupoints and safely insert needles are presented in acupuncture robot. The puncture robot with high technological similarity to acupuncture robot is getting mature, and a large number of human trials and animal experiments have been conducted for the development of puncture robot. Through comparing the similarities and differences between puncture robot and acupuncture robot in the aspects of through-skin puncture, needle insertion and needle removal, the valuable technology of puncture robot is analyzed for the development of acupuncture robot, and the crucial direction of technology migration is determined. ①Integrating the mechanical feedback and medical imaging technology and utilizing the multi-modal perception to achieve the safety of acupuncture operation. ②Emphasizing the integration of the existing designs of chest puncture robot to realize the acupuncture operation with inhalation and exhalation involved. ③Focusing on the development of relevant technology of automatic needle removal through conducting the actual scenario of treatment with acupuncture robot in patients under non-anaesthetic condition.

[Effect of electroacupuncture at "Tianshu" (ST25) on the regulation of nitrergic neurons in different intestinal segments in streptozotocin induced type 2 diabetic rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST25) on nitrergic neurons in jejunum and distal colon in type 2 diabetic rats, so as to explore its mechanism of regulating different intestinal segments. METHODS: Twenty-four SD rats were randomly divided into control, model and EA groups (n=8 in each group). The diabetes model was established by intraperitoneal injection of streptozotocin (35 mg/kg) and high-sugar and high-fat diet for 2 weeks. EA (2 Hz/15 Hz, 2 mA) was applied to bilateral ST25 for 20 min, once a day, 6 days a week for 4 weeks. The intestinal motility was evaluated by observing the first red stool excretion time and the distal colon bead excretion time. HE staining was used to observe the histological changes of jejunum and distal colon. The positive expression and protein expression of intestinal total neuronal marker protein gene product 9.5（PGP9.5） and neuronal nitric oxide synthase (nNOS) in jejunum and distal colon were detected by immunofluorescence staining and Western blot, respectively. RESULTS: After modeling, the blood glucose was significantly increased (P<0.01), the first red stool excretion time and the distal colon bead excretion time were shortened (P<0.01), the expression levels of PGP9.5 and nNOS in jejunum and distal colon were decreased (P<0.01) in the model group relevant to the control group. After treatment, compared with the model group, the blood glucose was decreased (P<0.01), the first red stool excretion time and the distal colon bead excretion time were prolonged (P<0.01, P<0.05), and the expression levels of PGP9.5 and nNOS in jejunum and distal colon were increased (P<0.05, P<0.01) in the EA group. HE staining showed disordered structure in intestinal mucosa of the jejunum and distal colon, and reduction of the number of goblet cells in the model group, which was relatively milder in the EA group. CONCLUSION: EA can effectively improve the intestinal mucosal damage and restore intestinal motor function in type 2 diabetic rats, which may be related to its function in regulating the number of nitrergic neurons in the intestinal nervous system.

[Investigation on the mechanism of acupuncture in treatment of diabetes mellitus type 2 based on the network of islet macrophages-pancreatic adipose cells-islet ß cells].

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet ß cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet ß cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.

[Research and development of intelligent medical equipment and internationalization of acupuncture and moxibustion: thoughts from researchers of acupuncture robot].

Under the background of artificial intelligence, the internationalization of acupuncture and moxibustion has braced an important opportunity. Intelligent medical equipment for acupuncture and moxibustion has entered from the laboratory into the clinic. However, the current research focuses on optimizing acupuncture treatment technology rather than innovating acupuncture theory. Internationally, the westernization of traditional acupuncture and the dilution of its characteristics are worrying. It is urgent to promote the China-led international standards of acupuncture and moxibustion and the patent protection of traditional acupuncture and moxibustion. Intelligent medical equipment will play the role of media, and promote the internationalization of traditional acupuncture and moxibustion with standardized and highly-integrated intelligent medical equipment for acupuncture and moxibustion, and integrate modern scientific and technological achievements. It is a feasible way for the internationalization of acupuncture and moxibustion.

[Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network].

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.

[An intelligent glass cupping device with closed-loop control].

As the living standard improves and population aging continues, the traditional cupping manipulations fail to meet the ever-growing demand for high-quality medical and health services. Aiming to address such shortcomings of traditional cupping manipulations as difficulty in achieving real-time temperature control, unsatisfactory negative pressure effect and inconve-nience to observe the internal situation, we have developed a glass cupping device with closed-loop control that could automatically integrate the acupoint-symptom analysis models. This device, composed of two cups, boasts high safety, good sealing and sound economic efficiency. The PT100 thermocouple probe and the pressure sensor equipped with P89C668 single chip microcomputer enable the multimodal integration of temperature and pressure, whose main parameters can be automatically displayed on the LED screen by the built-in data processing device. This glass cupping device with closed-loop control is an updated design for acupuncture and moxibustion based on multidisciplinary resources.

[Correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases].

OBJECTIVE: To observe the correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases. METHODS: In clinical research, 443 patients from 8 hospitals were recruited, including the outpatients and inpatients of Crohn's disease (n=143), ulcerative colitis (n=108), chronic appendicitis (n=87) and other intestinal diseases (n=105). The site with tenderness on the body surface and the morphological changes of local skin were observed and recorded in the patients. Using a sensory tenderness instrument, the pain threshold at the sensitization point was measured in 60 patients with ulcerative colitis. In animal experiment, SD rats were used and divided into a enteritis group (n=8), in which the enteritis model were established, and a control group (n=3), in which no any intervention was given. After the injection of Evans blue (EB) at caudal vein, the blue exudation points on the body surface were observed and the distribution rule was analyzed statistically. RESULTS: The referred pain on the body surface in the patients with intestinal diseases was mainly located in the lower abdomen (93.9%, 416/443), the lumbar region (70.9%, 314/443) and the lower legs (33.0%, 146/443). The diameter of tenderness region was 1.5 to 2.5 cm. Compared with the region without sensitization, the pain threshold of the sensitization point in the patients with ulcerative colitis was reduced significantly (P<0.001). The referred pain on the body surface in the patients with appendicitis was located in the right lower abdomen (97.7%, 85/87), the waist and back (54.0%, 47/87) and the right lower limbs on the medial side (71.3%, 62/87). The tenderness region was 1 to 2 cm in diameter and was irregular in form. After modeling of enteritis in the rats, the EB exudation points were visible from T12 to L2. CONCLUSION: Intestinal diseases induce referred pain on the body surface where is the same as or adjacent to the location of the spinal segment corresponding to the affected intestinal section. These sensitization regions are related to the locations of acupoints.

[Professor SHENG Can-ruo's academic thoughts and acupoint selection experience for hot flashes].

Professor SHENG Can-ruo is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor SHENG 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between yin and yang. While regulating yin and yang, more attention should be paid to ying-wei harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

Age shock index and age-modified shock index are strong predictors of outcomes in ST-segment elevation myocardial infarction patients undergoing emergency percutaneous coronary intervention.

BACKGROUND: Early identification of high-risk patients provides clinicians with greater decision-making time and better informs strategies to cope with disease. The predictive values of age shock index (age SI) and age-modified shock index (age MSI) in ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI) have rarely been reported, especially compared with those for SI, MSI, and the Global Registry of Acute Coronary Events (GRACE) risk score. PATIENTS AND METHODS: Nine hundred and eighty-three STEMI patients undergoing emergency PCI between January 2014 and September 2017 were analyzed in a retrospective cohort study. The primary outcomes were rates of in-hospital cardiovascular events, and 6-month and long-term all-cause mortality. RESULTS: In multivariate analyses, the predictive values of age SI and age MSI were comparable to that of the GRACE score, but superior to those of SI and MSI for in-hospital cardiac mortality [age SI: odds ratio (OR) = 1.05, P < 0.001, area under the receiver operating characteristic (ROC-AUC) = 0.805, P < 0.001; age MSI: OR = 1.04, P < 0.001, ROC-AUC = 0.813, P < 0.001; GRACE score: OR = 1.03, P < 0.001, ROC-AUC = 0.827, P < 0.001], 6-month all-cause mortality (age SI: OR = 1.04, P < 0.001, ROC-AUC = 0.791, P < 0.001; age MSI: OR = 1.03, P < 0.001, ROC-AUC = 0.801, P < 0.001; GRACE score: ROC-AUC = 0.828, P < 0.001), long-term all-cause mortality [age SI: hazard ratio (HR) = 1.06, P < 0.001, ROC-AUC = 0.798, P < 0.001; age MSI: HR = 1.04, P < 0.001, ROC-AUC = 0.84, P < 0.001; GRACE score: ROC-AUC = 0.822, P < 0.001] and post-discharge all-cause mortality (age SI: HR = 1.05, P < 0.001, ROC-AUC = 0.78, P = 0.001; age MSI: HR = 1.05, P < 0.001, ROC-AUC = 0.789, P < 0.001; GRACE score: ROC-AUC = 0.812, P < 0.001). CONCLUSION: Age SI and age MSI are stronger predictors than SI and MSI for in-hospital cardiovascular events, and 6-month and long-term all-cause mortality in STEMI patients undergoing emergency PCI. Age SI and age MSI appear to be convenient and simpler indicators than the GRACE score.

Risk scores for predicting dysphagia in critically ill patients after cardiac surgery.

BACKGROUND: This study aimed at developing and validating a scoring model to stratify critically ill patients after cardiac surgery based on risk for dysphagia, a common but often neglected complication. METHODS: Data were prospectively collected and analyzed from January 2016 to June 2017 from 395 consecutive post cardiac surgery patients at the cardiac care unit (CCU) at a single center; 103 (26.1%) developed dysphagia. Univariate and multivariate logistic analyses were used to identify independent predictors for dysphagia. The survival nomogram was developed on the basis of a multivariable Cox model, which allowed us to obtain survival probability estimations. The predictive performance of the nomogram was verified for discrimination and calibration. Areas under receiver operating characteristic curve analysis were used to illustrate and evaluate the diagnostic performance of the novel model. RESULTS: The final novel scoring model, named SSG-OD, consists of three independent factors: gastric intubation (OR = 1.024, 95% CI 1.015-1.033), sedative drug use duration (OR = 1.031, 95% CI 1.001-1.063) and stroke or not (OR = 6.182, 95% CI 3.028-12.617). SSG-OD identified patients at risk for dysphagia with sensitivity of 68.5% and specificity of 89.0% (OR = 0.833, 95% CI: 0.782-0.884). The positive and negative likelihood ratios were 6.22 and 0.35. CONCLUSIONS: The novel SSG-OD scoring system to risk stratify CCU patients for dysphagia is an easy-to-use bedside prognostication aid with good predictive performance and the potential to reduce aspiration incidence and accelerate recovery.

Acupuncture for behavioral changes of experimental depressive disorder: a systematic review and meta-analysis.

Acupuncture is considered to be a promising alternative therapy for depression. Nevertheless, up to now, it remains controversial on the effects exerted by acupuncture on behavioral changes in depression models. Consequently, it's necessary to develop a systematic review and meta-analysis to assess the effect of acupuncture for model rats of depression. Ultimately, 90 studies involving 1861 models were identified. Behavioral indicators including the number of crossings (NC) and the number of rearings (NR) in open field test (OFT), the capacity of sucrose intake (CSI) and the rate of sucrose intake (RSI) in sucrose intake test (SIT), final weight (FW) and gain weight (GW) were employed as main outcomes in depression model rats. The pooled results showed that acupuncture had not less effect than western medicine on improving NC, NR, FW, GW, RSI (P > 0.05). However, the CSI improvement was poorer compared with west medicine (P < 0.05). In conclusion, acupuncture has not less effect on behavior changes than western medicine, including improving NC, NR, RSI, FW and GW in depression models.