Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

Objective To explore the property of projection neurons in the pathway from the medial prefrontal cortex(mPFC)to the thalamic paraventricular nucleus(PVT)and to investigate the effect of modulation of the pathway on physiological pain and acute pain in mice.Methods Three knock-in mice with glutamate decarboxylase 67-green fluorescent protein(GAD67-GFP)were used in morphological tracing experiments,and twenty-seven C57 mice were used for behavioral observation experiments.Cholera toxin subunit B(CTB)was injected into the PVT of GAD67-GFP transgenic mice,and the properties of mPFC neurons projected to PVT were observed.The mPFC-PVT pathway was activated or inhibited by chemogenetics to observe the effects on physiological pain,such as mechanical pain,thermal pain,cold pain,and on acute inflammatory pain induced by capsaicin in mice.Results CTB-labeled neurons in the mPFC were mainly distributed in layer Ⅴ and layer Ⅵ and not double-labeled with GAD67-GFP.Chemogenetic activation of the mPFC-PVT pathway decreased the mechanical pain threshold significantly(P＜0.0001)and shortened the thermal pain latency(P＜0.001),but had no obvious effects on cold pain.Inhibition of this pathway increased the mechanical pain threshold significantly(P＜0.05).Activation of the pathway increased the paw licking time(P＜0.05)in acute inflammatory pain induced by capsaicin.Conclusion mPFC-PVT pathway is a non GABAergic projection and its activation can promote mechanical pain,thermal pain,and acute inflammatory pain induced by capsaicin in mice.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Objective:To analyze and evaluate the current situation of falls in the frail elderly population, and to provide a reliable basis for formulating measures for fall prevention.Methods:CNKI, VIP Database, Wanfang Database, China Biomedical Database, PubMed, Embase, Web of Science, CINAHL, Cochrane Library, Sinomed were searched, and cross-sectional studies on falls in the frail elderly population were searched, and the search time limit was established until June 30, 2023. Two review authors independently screened studies, extracted data, assessed the risk of bias of included studies, and Meta-analyses were performed using Stata 16.0 software and RevMan5.4.Results:A total of 12 cross-sectional studies with a total sample size of 4 597 cases were included. Meta-analysis showed that the incidence of falls in the frail elderly population was 39.9% (1 834/4 597). The results of subgroup analysis showed that there was significant difference in the female, age, chronic pain, body mass index, live alone ( P<0.05). The incidence of falls in male and female was 25.9%(640/2 471) and 40.7%(1 005/2 471), respectively. The incidence of falls in the aged 60-69, 70-79 and over 80 years old was 25.7%(470/1 831), 30.6% (560/1 831) and 46.8%(857/1 831), respectively. The incidence of falls in body mass index < 18.5, 18.5-24.0, >24.0 kg/m 2 was 12.29%(63/512), 9.58%(49/512) and 19.89%(101/512), respectively. The incidence of falls in with or without chronic pain was 33.55%(181/541) and 16.03%(87/541), respectively. The incidence of falls in living alone and not living alone was 32.3%(524/1 624) and 16.9%(274/1 624), respectively. Conclusions:The incidence of falls in the frail elderly population is at a relatively high level. Women, older adults, overweight, have chronic pain and live alone have a higher incidence of falls.

This article seeks to delve into the correlation between pituitary neuroendocrine tumors(PitNET)and neuropsychiatric disorders while summarizing the most recent advancements in related research.Some patients with PitNET,benign tumors arising from pituitary gland cells,may develop specific clinical symptoms due to either tumor compression or abnormal hormone secretion.In recent years,investigators have identified a significant association between PitNET and neurological as well as psychiatric disorders.Patients with PitNET frequently manifest neurological and psychiatric symptoms,including depression,anxiety,and cognitive impairment,significantly impacting their quality of life and prognosis.These symptoms may be associated with distorted body image,hormonal imbalances,and inadequate treatment.The holistic approach to PitNET encompasses surgical intervention,radiation therapy,and drug therapy,each with its distinct set of advantages and drawbacks.Presently,transsphenoidal resection stands out as the most frequently employed method in treating PitNET to ameliorate the patient's neurological and psychiatric disorders.However,the use of dopamine agonists(DAs)in the treatment of prolactin(PRL)tumors and growth hormone(GH)adenomas may potentially induce or exacerbate neurological and psychiatric symptoms.The impact of radiation therapy on PitNET patients varies depending on the radiation dose and treatment area.Given that both the PitNET disease itself and its treatment may lead to neurological and psychiatric disorders,it is essential to assess and address the neurological and psychiatric status of all PitNET patients.Careful consideration should be given to PitNET patients with neurological and psychiatric disorders to determine whether these issues stem from dopamine agonist(DAs)treatment.The primary consideration should be given to patients with PRL microadenomas with normal PRL levels to minimize the dose of bromocriptine or cabergoline to the most effective level or even discontinue the medication with subsequent follow-up.Caution is advised when considering the discontinuation or reduction of medication for PRL large adenomas.A gradual reduction approach may be undertaken based on related factors such as PRL levels and tumor size.Close follow-up through monitoring patient PRL levels and enhanced pituitary MRI is crucial to prevent tumor enlargement following the reduction of medication.While some PitNET patients have experienced improvement or recovery from neurological and psychiatric disorders through personalized comprehensive treatment,it is important to note that certain patients may exhibit irreversible symptoms.Currently,research on the combination of PitNET and neuropsychiatric disorders remains relatively limited.Moving forward,it is imperative to delve deeper into its pathogenesis,aiming to enhance diagnostic methods for neuropsychiatric disorders in PitNET patients.This includes refining and updating diagnostic criteria and expanding intervention methods.These efforts are crucial in mitigating the incidence of PitNET in conjunction with neuropsychiatric disorders,ultimately improving the overall quality of life for patients.

Objective:To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment.Methods:It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission.Results:This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males ( χ2=22.479, P<0.001), age ( Z=-2.521, P=0.012), systolic blood pressure ( Z=-4.148, P<0.001), diastolic blood pressure ( Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer ( Z=-7.019, P<0.001), total cholesterol ( Z=-8.796, P<0.001), triglyceride ( Z=-6.158, P<0.001), low density lipoprotein cholesterol ( Z=-8.716, P<0.001), serum creatinine ( Z=-7.368, P<0.001), serum C3 ( Z=-3.663, P<0.001), serum C4 ( Z=-6.560, P<0.001), proportion of glucocorticoid use ( χ2=116.417, P<0.001) and proportion of immunosuppressant use ( χ2=53.839, P<0.001) were all higher, while serum albumin ( Z=12.518, P<0.001), estimated glomerular filtration rate ( Z=6.345, P<0.001) and serum IgG ( Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L ( HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues ( HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues ( HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions:The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.
Male ; Humans ; Adult ; Middle Aged ; Female ; Coronary Artery Disease/complications* ; Cholesterol, HDL ; Cholesterol, LDL ; Prospective Studies ; Myocardial Infarction/etiology* ; Stroke ; Risk Factors