Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Objective To investigate the relationship between serum adiponectin levels and body composition of perimenopausal and postmenopausal women in central and western Gansu province, and explore the influencing factors of adiponectin levels. Methods The body weight, body mass index(BMI), waist-to-hip, fat mass, percentage of body fat, visceral fat mass and muscle mass of 638 women(317 in perimenopausal period and 321 in postmenopausal period) in central and western Gansu were measured by bioelectrical impedance analyzer. Enzyme linked immunosorbent assay (ELISA)was used to measure serum adiponectin levels. Pearson correlation analysis and multiple liner regression were used to investigate the relationship between adiponectin levels and body composition. Results The body muscle mass of women living in central and western Gansu province showed a downward trend after menopause period compared to those who were in perimenopause. The waist circumference, waist-hip ratio, percentage of body fat, visceral fat mass of postmenopauseal women showed an increasing trend compared to perimenopausal. There were no significant differences in BMI, fat mass and serum adiponectin levels. Overall, serum adiponectin levels were positively correlated with body fat percentage and visceral fat mass, and negatively correlated with muscle mass, and the main influencing factors of serum adiponectin levels were visceral fat mass. Conclusion The main influencing factors of serum adiponectin levels in perimenopausal and postmenopausal women living in central and western Gansu province are the visceral fat mass.

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.
Awareness ; Brain ; Consciousness ; Humans ; Oxygen ; Visual Perception

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Objective:To observe the effects of Scutellariae Radix-Hedyotidis Herba on the proliferation of human lung adenocarcinoma A549 cells and the expression of interleukin-6（IL-6）， phosphatidylinositol 3-kinase （PI3K），protein kinase B （Akt）， p-protein kinase B （p-Akt）， mechanistic target of rapamycin （mTOR）， hypoxia-inducible factor-1α （HIF-1α）， and Cyclin D₁ at the cellular level， and to explore their molecular mechanism. Method:Following the set-up of the blank group （complete medium）， low-， moderate-，and high-dose （20， 40， and 60 mg·L^-1） Scutellariae Radix-Hedyotidis Herba groups， and low-， moderate-， and high-dose （5， 10， and 20 mg·L^-1） cisplatin groups， the cell were treated with the corresponding drugs for 24， 48， and 72 h for detecting their viability by tetrazolium bromide （MTT） colorimetry. A549 cells were then divided into the blank group， Scutellariae Radix-Hedyotidis Herba group， cisplatin group， and combined medication group and intervened with the complete medium， 40 mg·L^-1 Scutellariae Radix-Hedyotidis Herba， 10 mg·L^-1 cisplatin， and 40 mg·L^-1 Scutellariae Radix-Hedyotidis Herba + 10 mg·L^-1 cisplatin， respectively， for 24， 48 and 72 h， followed by the measurement of inhibitory effects against the proliferation of A549 cells in each experimental group. The level of IL-6 in cell culture supernatant was determined by enzyme-linked immunosorbent assay （ELISA） after 72 h. The mRNA expression levels of HIF-1α and Cyclin D₁ in each group were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of PI3K， Akt， p-Akt， mTOR， HIF-1α， and Cyclin D₁ by Western blot. Result:After 24 h intervention， Scutellariae Radix-Hedyotidis Herba did not significantly inhibit the proliferation of A549 cells. However， 48 h later， the inhibitory effect in Scutellariae Radix-Hedyotidis Herba groups were significantly enhanced in comparison with that in the blank group （P<0.05）， exhibiting a time-dependent response. After 72 h of action， no significant change was present in the inhibitory effect of each Scutellariae Radix-Hedyotidis Herba group， so the optimal concentration of Scutellariae Radix-Hedyotidis Herba was set at 40 mg·L^-1 for follow-up experiments. As demonstrated by the comparison with the blank group， cisplatin at each concentration inhibited the cell proliferation in a time-dependent manner （P<0.05）. Considering the cell survival rate， the best concentration of cisplatin was set at 10 mg·L^-1. Compared with the blank group， Scutellariae Radix-Hedyotidis Herba combined with cisplatin remarkably inhibited the proliferation of A549 cells in a time-dependent manner （P<0.05）， and the differences between the combined medication group and the other two groups became more significant after 72 h of medication （P<0.01）. The IL-6 level in each experimental group， especially in the combined medication group， significantly declined in contrast to that in the blank group （P<0.01）. The mRNA expression levels of HIF-1α and Cyclin D₁ in all experimental groups were obviously lower than those in the blank group， with the most significant changes observed in the combined medication group （P<0.05，P<0.01）. The protein expression levels of PI3K， p-Akt， mTOR， HIF-1α， and Cyclin D₁ in each experimental group was significantly down-regulated（P<0.05，P<0.01）， and the levels in the combined medication group were even lower than those in the cisplatin group （P<0.01）. Conclusion:Scutellariae Radix-Hedyotidis Herba has an inhibitory effect on the proliferation of A549 cells， which may be related to its inhibition against the expression and secretion of IL-6/PI3K/Akt/mTOR-HIF-1α axis.

Qingxin Lianzi Yin （QXLZY）， as an ancient classical formula for clearing the heart and nourishing the Yin， was composed of nine herbs （Scutellariae Radix， Ophiopogonis Radix， Lycii Cortex， Plantaginis Semen， Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma）， coming from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It could clear away the heart-fire， promote the interaction of the heart and kidney， replenish Qi and Yin， and stop strangury-turbidity. It was used to treat gonorrhea of urination， seminal emission， restlessness， wasting-thirst and so on. At present， the usage and dosage of QXLZY and its addition and subtraction are different in clinical practice. Most of the studies just focus on its clinical efficacy， and there is few review literature reflecting its historical evolution. Based on this， this paper systematically clarified the historical evolution， composition， preparation， interpretation， function， and modern clinical application of QXLZY. This work has been explained the historical evolution of QXLZY， and found that it was wildly used in modern clinical， especially suitable for the treatment of chronic urinary system diseases. At the same time， QXLZY also had significant therapeutic effects on neurasthenia， stomatitis， diabetic nephropathy and other aspects. Through the comprehensive analysis of ancient and modern literature， this work explores the true connotation of QXLZY from the perspective of traditional Chinese medicine theory， which can point out the direction of the clinical application and positioning of this famous classical formula after it comes into the market， and also can provide reference basis for its subsequent in-depth research and development.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Aim To establish three kinds of DNA damage models of mouse testicular spermatogonia cell line GC-1 cells and analyze their similarities and differences. Methods GC-1 cells were treated with UVB irradiation, D-galactose(D-Gal) or bleomycin (BLM), respectively. Then the expression and localization of 'Y-H2AX were detected by Western blot and immunofluorescence, the expression and localization of 8-OHdG were measured by immunofluorescence, and the expression levels of p-p53 and p21 were measured by Western blot. Results The expression of -y-H2AX in GC-1 cell reached to the peak 4 h after UVB irradiation and 6 h after D-Gal stimulation, whereas -y-H2AX expression gradually increased after BLM stimulation, and the higher the concentration of BLM,the shorter the time to reach the peak. The results of immunofluorescence showed that 8-OHdG expression was observed in the nucleus and cytoplasm of GC-1 cells after UVB irradiation and BLM stimulation, and the longer the culture time, the more the expression in the nucleus. In contrast, the expression of 8-OHdG was observed in the cytoplasm and reached the peak at 6 h in the D-Gal stimulated GC-1 cells. After UVB irradiation, the protein expression levels of p-p53 gradually increased, while p21 protein expression appeared later than that of p-p53; in the D-Gal stimulated GC-1 cells, the protein expression levels of p-p53 reached the peak at 6 h, and p21 protein expression reached the peak at 12 h; after low concentration BLM stimulation, the protein expression levels of p-p53 and p21 continuously increased, and after high concentration BLM stimulation, the protein expression levels of p-p53 and p21 reached its peak at 2 h, then decreased at 4 h. Conclusions Three kinds of DNA damage models of GC-1 cells are successfully established, and the DNA damage in GC-1 cells treated with D-Gal is mild, while the DNA damage in GC-1 cells treated by UVB irradiation and BLM stimulation is more severe.

Pazufloxacin eardrops are a topical quinolone agent for the treatment of outer ear infection. The present study evaluated the pharmacokinetics and topical distribution of pazufloxacin eardrops by a sensitive LC-MS/MS method for determining pazufloxacin in plasma and otorrhea. Plasma and otorrhea samples were extracted by acetonitrile-induced protein precipitation and were subjected to liquid chromatography-tandem mass spectrometric analysis with an electrospray ionization interface. The samples were separated on an HSS T₃ column (50 mm×2.1 mm, 1.8 μm). To avoid the matrix effect, gradient elution was performed with the mobile phase consisting of methanol and 1 mmol·L^-1 ammonium acetate aqueous solution (0.1% formic acid). The ion transitions for pazufloxacin and pazufloxacin-d₄ were m/z 319.1→281.2 and m/z 323.1→285.2, respectively, under the multiple reaction monitoring (MRM) mode. The method was linear in the range of 0.010 0 - 8.00 ng·mL^-1 for pazufloxacin in plasma and 0.500 - 1 000 ng·mg^-1 in otorrhea. The intra- and inter-day accuracy and precision for pazufloxacin in plasma and in otorrhea met acceptable criteria. The clinical trial was approved by the Society of Ethics and conducted in Nanjing First Hospital and Jiangsu Province Hospital. The validated methods were used in a systemic and topical pharmacokinetic study of 0.1% pazufloxacin eardrops in 3 patients with chronic suppurative otitis media.