Electroacupuncture ameliorates cognitive impairment in APP/PS1 mouse by modulating TFEB levels to relieve ALP dysfunction.

Recently, the underlying mechanisms of acupuncture on the effects of Alzheimer's disease (AD) treatment have not been fully elucidated. Defects in ALP (autophagy-lysosomal pathway) and TFEB (transcription factor EB) play critical roles in AD. Our previous studies have demonstrated that electroacupuncture (EA) can ameliorate both ß-amyloid (Aß) pathology and cognitive function in APP/PS1 mice. However, the effects of EA on the expression of ALP and TFEB and their potential mechanisms require further investigation. Twenty-eight male APP/PS1 mice were randomly divided into Tg and Tg + EA groups, and 14 C57BL/6 mice served as the wild-type (WT) group. After 1 week of adaptation to the living environment, mice in the Tg + EA group were restrained in mouse bags and received manual acupuncture at Baihui (GV20) acupoint and EA stimulation at bilateral Yongquan (KI1) acupoints, using the same restraint method for WT and Tg groups. The intervention was applied for 15 min each time, every other day, lasting for six weeks. After intervention, the spatial learning and memory of the mice was assessed using the Morris water maze test. Hippocampal Aß expression was detected by immunohistochemistry and ELISA. Transmission electron microscopy (TEM) was used to observe autophagic vacuoles and autolysosomes in the hippocampus. Immunofluorescence method was applied to examine the expression of TFEB in CA1 region of the hippocampus and the co-localization of CTSD or LAMP1 with Aß. Western blot analysis was performed to evaluate the changes of LC3, p62, CTSD, LAMP1, TFEB and n-TFEB (nuclear TFEB) in the hippocampus. The findings of behavioral assessment indicated that EA alleviated the cognitive impairment of APP/PS1 mice. Compared with the WT group, the Tg group showed significant cognitive decline and abnormalities in ALP and TFEB function (P < 0.01 or P < 0.05). However, these abnormal changes were alleviated in the Tg + EA group (P < 0.01 or P < 0.05). The Tg group also showed more senile plaques and ALP dysfunction features, compared with the WT group, and these changes were alleviated by EA. In conclusion, this study highlights that EA ameliorated Aß pathology-related cognitive impairments in the APP/PS1 model associated with ALP and TFEB dysfunction.

A systematic review and meta-analysis of observational studies of the association between the use of incretin-based therapies and the risk of pancreatic cancer.

BACKGROUND: Some early reports in the medical literature have raised concern about a possible increased risk of pancreatic cancer associated with the use of two broad classes of incretin-based therapies, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 receptor agonists. This possibility has been somewhat mitigated by the null findings meta-analyses of randomized controlled trials, but the usefulness of their findings was hampered by serious shortcomings of lack of power and representativeness. These shortcomings can typically be addressed by observational studies, but observational studies on the topic have yielded conflicting findings. A systematic review and meta-analysis of observational studies was performed to qualitatively and quantitatively appraise the totality of evidence on the association between the use of incretin-based therapies and the risk of pancreatic cancer in routine clinical practice. METHODS: The PubMed, Web of Science, Embase, and Google Scholar databases were searched. The study quality was appraised using the ROBINS-I tool and based on the presence of pharmacoepidemiology biases. A random-effects model was used to estimate the summary relative risks with corresponding CIs. RESULTS: A total of 14 studies were included. The qualitative assessment revealed that all studies had inadequate follow-up (≤5 years), 12 studies were suspected to suffer from time-lag bias (due to inappropriate choice of comparator group) to varying extent, five studies included prevalent users, five studies did not implement exposure lag period, five studies had a serious risk of bias due to confounding, and one study had a time-window bias. The quantitative assessment showed no indication of an increased risk when all studies were pooled together (RR 1.04, 95% CI 0.87, 1.24) and when the analysis was restricted to the studies with the least bias (RR 0.77, 95% CI 0.51, 1.17). However, the pooled RRs were more frequently higher in the studies with less rigorous design and analysis. Specifically, a tendency toward an increased risk was observed in the studies with (RR 1.34, 95% CI 1.04, 1.72) or possibly with (RR 1.10, 95% CI 0.89, 1.36) time-lag bias, in the studies that did not apply (RR 1.23, 95% CI 0.93, 1.63) or with potentially inadequate exposure lag period of 6 months (RR 1.13, 95% CI 0.66, 1.94), in the studies that inappropriate comparator group of a combination of unspecified (RR 1.49, 95% CI 1.25, 1.78) or non-insulin (RR 1.15, 95% CI 0.93, 1.42) antidiabetic drugs, and in the studies with serious risk of bias due to confounding (RR 1.18, 95% CI 0.56, 2.49). CONCLUSIONS: In summary, the totality of evidence from observational studies does not support the claim that the use of incretin-based therapies is associated with an increased risk of pancreatic cancer in routine clinical practice. The increased risk of pancreatic cancer observed in observational studies reflects bias resulting from suboptimal methodological approaches, which need to be avoided by future studies.

Clinical significance of tumor abnormal protein in patients with type 2 diabetes complicated with lung adenocarcinoma in situ.

BACKGROUND: To investigate the application value of tumor abnormal protein in patients with type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. MATERIALS AND METHODS: A total of 140 patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ (Group A), 160 patients with type 2 diabetes mellitus (Group B), and 120 healthy controls (Group C) were enrolled in the Department of Thoracic Surgery of the First Affiliated Hospital of Soochow University from November 2021 to December 2022. RESULTS: The total cholesterol level was higher in Group A than in Group B (p < 0.05) and Group C (p < 0.01), and it was higher in Group B than in Group C (p < 0.01). The comparison results of cholesterol level were similar to those of tumor abnormal protein, low-density lipoprotein cholesterol, and glycosylated hemoglobin among the three groups. The triglyceride level was higher in Group A than in Group B and Group C (both p < 0.01). Group A had a higher level of high-density lipoprotein cholesterol than Group C (p < 0.01). The fasting plasma glucose level was higher in Group A than in Group B and Group C (both, p < 0.01). These findings indicated that tumor abnormal protein, glycosylated hemoglobin, high-density lipoprotein cholesterol, and fasting plasma glucose were independent factors for patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. CONCLUSION: Therefore, detecting tumor abnormal protein levels may help diagnose lung adenocarcinoma in situ in patients with type 2 diabetes mellitus.

The study found that tumor abnormal protein, glycosylated hemoglobin, high-density lipoprotein cholesterol, and fasting plasma glucose were independent factors for patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. Detecting tumor abnormal protein levels may help diagnose lung adenocarcinoma in situ in patients with type 2 diabetes mellitus.

"Seminal testosterone", rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study.

Objective: Reproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied. Methods: A bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor's analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time. Results: The b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients' results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest. Conclusion: Seminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463.

Clinical Significance of Thrombelastography Results in Patients with Lung Adenocarcinoma in Situ Complicated with Type 2 Diabetes.

To investigate the significance of thrombelastography (TEG) in patients who have lung adenocarcinoma in situ (LAIS) complicated with type 2 diabetes (T2D), 120 subjects were enrolled: 40 with LAIS, 40 with LAIS and T2D (LAIS + T2D), and 40 healthy controls (HCs). Correlation analysis was used to assess the relationships of TEG with indicators of T2D. The LAIS + T2D group had lower reaction time (R), rate of clot formation (K), estimated percentage of lysis (EPL), and lysis after 30 min (LY30), but higher maximum amplitude (MA), angle (α), and coagulation index (CI) than other group. Compared with the HC group, the LAIS group had lower R, K, EPL, and LY30, but higher MA, α, and CI. In LAIS + T2D group, R and LY30 had negatively correlations with fasting blood glucose (FBG) and triglycerides (TGs); α and MA had positive correlations with FBG and TG; K had negative correlations with FBG; EPL had negative correlations with FBG and low-density lipoprotein (LDL); and CI had positive correlations with FBG and LDL. TEG may be a useful indicator of blood coagulation dysfunction in these patients rather the healthy individuals.

Correlation of serum delta-like ligand-4 level with the severity of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is one of the most serious microvascular complications of type 2 diabetes mellitus (T2DM). Delta-like ligand-4 (DLL4) maintains the normal physiological microenvironment of the retina. However, the relationship between the level of DLL4 and the severity of DR remains unclear. METHODS: We retrospectively analyzed serum DLL4 levels and other laboratory and clinical data in 94 T2DM patients (35 patients without DR [NDR], 32 with non-proliferative DR [NPDR], 27 with proliferative DR [PDR]), and 30 healthy controls. RESULTS: The serum DLL4 level was significantly greater in the NDR group (43.38 ± 16.23 pg/mL), NPDR group (56.57 ± 25.89 pg/mL), and PDR group (74.97 ± 25.28 pg/mL) than in the healthy controls (29.9 ± 8.92 pg/mL; all p < 0.05). Among T2DM patients, the level of DLL4 increased as the severity of DR increased (p < 0.05). Logistic regression analysis demonstrated that DR was positively associated with DLL4, glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), and duration of T2DM (all p < 0.05). Consistently, receiver operating characteristic (ROC) curve analysis also indicated that DLL4 was a potential candidate biomarker for identifying the severity of DR. CONCLUSIONS: T2DM patients, especially those with DR, have increased serum levels of DLL4. DLL4 may be used as a biomarker and an independent risk factor for DR, and targeting DLL4 may be a potential therapy in patients with DR.

Risk Factors for Albuminuria in Normotensive Older Adults with Type 2 Diabetes Mellitus and Normal Renal Function: A Cross-Sectional Study.

INTRODUCTION: Diabetes mellitus (DM) is prevalent in developed and developing countries, including China. However, few studies have examined the potential risk factors for albuminuria in normotensive older adults with type 2 DM and normal renal function. METHODS: We recruited normotensive older adults (≥ 65 years) with type 2 DM and normal renal function from the First Affiliated Hospital of Soochow University from January to December 2019. We stratified participants according to their urine albumin to creatinine ratio (ACR) into the following groups: normal ACR (ACR1), microalbuminuria (ACR2), and macroalbuminuria (ACR3). Demographic characteristics, anthropometric parameters, and metabolic profiles were recorded. Creatinine clearance (Ccr) and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. Logistic regression was used to examine risk factors for albuminuria. RESULTS: A total of 250 older adults were enrolled during the study period, including 124, 82, and 44 with normal albuminuria, microalbuminuria, and macroalbuminuria, respectively. We found that an extended duration of DM (odds ratio [OR] 1.085, 95% confidence interval [CI] 1.012-1.164, P = 0.022), elevated systolic blood pressure (OR 1.049, 95%CI 1.018-1.081, P < 0.01), elevated glycated hemoglobin (OR 1.734, 95% CI 1.332-2.258, P < 0.01), low insulin (OR 0.871, 95% CI 0.804-0.944, P < 0.01), and low C-peptide (OR 0.365, 95% CI 0.239-0.588, P < 0.01) were independent risk factors for albuminuria. CONCLUSION: Elevated blood pressure, low insulin, low C-peptide, and poor glycemic control were significant risk factors for albuminuria. These parameters may serve as early indicators for intervention.

Consumers' satisfaction factors mining and sentiment analysis of B2C online pharmacy reviews.

BACKGROUND: In recent years, online pharmacies have been accepted by increasingly more consumers, and the prospects for online pharmacies are optimistic. This article explores the consumers' satisfaction factors addressed in Business to Customer (B2C) online pharmacy reviews and analyzes the sentiments expressed in the reviews. The goal of this work is to help B2C online pharmacy enterprises identify consumers' concerns, continuously improve the health services level. METHODS: This article was based on the Latent Dirichlet Allocation (LDA) topic model. From a third-party platform-based B2C online pharmacy and a proprietary B2C online pharmacy (JD Pharmacy and J1.COM, respectively), 136,630 pieces of over-the-counter (OTC) drug review data posted from January 1, 2015 to December 31, 2018 were selected as samples and used to explore the satisfaction factors of B2C online pharmacy consumers regarding the entire drug purchasing process. Then, the sentiments expressed in the drug reviews were analyzed with SnowNLP. RESULT: Categorization of the 12 factors identified by LDA showed that 5 factors were related to logistics; these 5 factors, which also included the most drug reviews, made up 38.5% of the reviews. The number of factors related to drug prices was second, with 3 factors, and reviews of drug prices made up 25.5% of the reviews. Customer service and drug effects each had two related factors, and a smaller percentage of these reviews (13.95%) were related to drug effects. Consumers still maintain positive opinions of JD Pharmacy and J1.COM. However, some opinions on logistics and drug prices are expressed. CONCLUSION: The most important task for online pharmacies is to improve logistics. It is better to develop self-built logistics. Both types of B2C online pharmacies can improve consumer viscosity by implementing marketing strategies. With regard to customer service, focusing on improving employees' service attitudes is necessary.

Serum von Willebrand factor for early diagnosis of lung adenocarcinoma in patients with type 2 diabetes mellitus.

BACKGROUND: The elevation of plasma von Willebrand factor (vWF) has been proposed to be a predictor of lung cancer. Type 2 diabetes mellitus (T2DM) causes endothelial activation, resulting in the secretion of vWF. However, the role of vWF in patients with T2DM complicated with lung cancer remains unclear. AIM: To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ (AIS). METHODS: This study enrolled 43 patients with T2DM combined with lung AIS (T2DM + AIS group), 43 patients with T2DM alone (T2DM group), 43 patients with lung AIS alone (AIS group), and 43 healthy volunteers (control group). The serum levels of vWF, insulin-like growth factor 1, and insulin-like growth factor binding protein 3 were determined. Multiple linear stepwise regression was performed to determine the correlations among variables. RESULTS: Serum concentration of vWF in the T2DM + AIS group was significantly higher than those in the T2DM, AIS, and control groups (P < 0.05). Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group (P < 0.05). There was no significant difference in serum vWF level between the T2DM and AIS groups. In the T2DM + AIS group, serum vWF was independently associated and positively correlated with serum levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 (P < 0.05). CONCLUSION: Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.

Data Mining of the Reviews from Online Private Doctors.

Background: User-generated content shared in the online health communities (OHCs) is becoming a valuable resource for researchers to understand patients' decision-making behaviors in the management of their health. Many studies have focused on how to obtain useful information from online reviews in OHCs. Introduction: This study focuses on a telemedicine service called Online Private Doctor (OPD), which is offered by a leading Chinese physician review website (PRW). OPD reviews have not received much attention. By data mining the reviews, our goal is to determine what patients are talking about when they use the OPD service and whether they are satisfied with the service or not. Materials and Methods: We used a Python web crawler to collect 41,029 reviews and 84,510 short reviews (labels) of all 5,645 physicians who offered the OPD service on a PRW (haodf.com) in China. Mixed methods (i.e., a literature review, topic discovery, annotation, and a sentiment analysis) were used to determine the information that the OPD reviews are meant to express. Results: We discovered that the OPD reviews can be categorized into four subjects: competence (35.1%), communication (29.4%), treatment (26.0%), and convenience (9.5%). In terms of previously discovered topics, we found that competence, communication, and treatment have been discussed before, but convenience is an emerging subject. The sentiment analysis indicated that 93.67% of the reviews indicated positive emotions, and the area under the receiver operating characteristic (ROC) curve is 0.64. Furthermore, the labels indicated that only 0.72% (603/84,570) of reviews were negative toward the OPD service. The subjects of the labels were distributed according to competence (34.7%), communication (23.8%), treatment (33.5%), and convenience (8.0%). Discussion: The findings of our study suggest that patients who ever used OPD have been quite satisfied with the service. From their reviews, we discovered that OPD has its special characteristics and is convenient. However, it still has some shortcomings, for example, the quality of the phone connection. In terms of both the platform and the doctors, more efforts should be made to make the OPD better and more regulated. Conclusion: OPD is an emerging telemedicine service that still needs more time and space to evolve. For patients, it helps reduce problems such as scheduling and queuing. Therefore, it brings more convenience to people's daily lives. In the future, more attention should be paid to this service, as it is helpful in reducing the uneven distribution of medical resources.

Marfan syndrome with type 2 diabetes mellitus: A case report from China.

RATIONALE: Marfan syndrome (MFS) is a genetic disorder of the connective tissue. MFS has an incidence of about 2 to 3 persons per 10,000 population. MFS is characterized majorly by the involvement of the eyes, skeletal muscles, and cardiovascular system. There are limited case reports of co-existence of MFS and type 2 diabetes mellitus (T2DM). PATIENT CONCERNS: A 16-year-old male patient who got admitted to our hospital with complaints of loss of vision from left eye for the last 3 days.Diagnosis of MFS along with luxation of left eye lens, and T2DM were made according to the patient's symptoms, signs, biochemical results, and ultrasonography. INTERVENTIONS: The patient received "vitrectomy (posterior approach (left eye)) + cataract extraction (left eye) + intraocular lens implantation (left eye) surgery" for luxation of left eye lens. The patient received "Bentall Operation" for MFS, and was prescribed warfarin 5 mg qod and spironolactone 20 mg bid during the follow-up period. The patient received continuous subcutaneous insulin infusion (CSII) during hospitalization, and then changed to insulin glargine preparation during the follow-up period. OUTCOMES: The vision was restored after the eye surgery and the patient also recovered well after the Bentall Operation. Additionally, there were no obvious complications during hospitalization and the follow-up period. Blood glucose levels were within normal range. LESSONS: There is a need to improve the recognition of MFS among school and community doctors. Early detection, diagnosis, and treatment of this rare disease can improve the quality of patient's life.

Chemical fingerprint of Ganmaoling granule by double-wavelength ultra high performance liquid chromatography and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

A method incorporating double-wavelength ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed for the investigation of the chemical fingerprint of Ganmaoling granule. The chromatographic separations were performed on an ACQUITY UPLC HSS C18 column (2.1 × 50 mm, 1.8 µm) at 30°C using gradient elution with water/formic acid (1%) and acetonitrile at a flow rate of 0.4 mL/min. A total of 11 chemical constituents of Ganmaoling granule were identified from their molecular weight, UV spectra, tandem mass spectrometry data, and retention behavior by comparing the results with those of the reference standards or literature. And 25 peaks were selected as the common peaks for fingerprint analysis to evaluate the similarities among 25 batches of Ganmaoling granule. The results of principal component analysis and orthogonal projection to latent structures discriminant analysis showed that the important chemical markers that could distinguish the different batches were revealed as 4,5-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4-O-caffeoylquinic acid. This is the first report of the ultra high performance liquid chromatography chemical fingerprint and component identification of Ganmaoling granule, which could lay a foundation for further studies of Ganmaoling granule.