Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

The role of glucose metabolism reprogramming and its targeted therapeutic agents in inflammation-related diseases / 药学学报

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Repeatability of wavefront aberration measured by adaptive optics visual simulator and agreement of OPD-Scan Ⅲ / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.

Inhibition of HSP70 release by geniposide improves angiogenesis in moist heat arthralgia spasm syndrome collagen induced arthritis rats / 中国药理学通报

Aim To investigate the relation between the effect of geniposide (GE) in improving angiogenesis in arthralgia spasm syndrome collagen induced arthritis (CIA) rats and the modulation of heat shock proteins 70 (HSP70) release. Methods A CIA model was constructed by multiple intradermal injections of complete Freund's adjuvant (CFA) and an equal volume mixture of chicken type II collagen (CCII) into the dorsal and caudal root regions of rats, on the basis of which a rheumatic fever stimulus was given to build up a moist heat arthralgia spasm syndrome in CIA rats. After successful modeling, the groups were randomly grouped, and the administered groups were gavaged with GE (60, 120 mg · kg

Effect of enriched environment combined with acupuncture at head points on behavior in rats with autism spectrum disorder / 中国康复理论与实践

ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.

Clinicopathological features of intravascular large B-cell lymphoma and collision tumors of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.

Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O2⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO‒) generated from the co-existence of NO and O2⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.

Mechanism of Flavonoids in Patriniae Herba in Affecting Occurrence and Development of Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is a common malignant tumor in the digestive system， ranking third in incidence and second in the cause of death worldwide. In recent years， the incidence of colorectal cancer is on the rise， and the age of patients with colorectal cancer tends to be younger， with a heavy cancer burden. It is of great significance to prevent the occurrence， development， recurrence， and metastasis of colorectal cancer to reduce the incidence and mortality of colorectal cancer. Patriniae Herba has the effects of clearing heat， removing toxins， eliminating carbuncle， and discharging pus and shows good therapeutic efficacy on inflammatory bowel disease， digestive tract tumors， pelvic inflammation， gynecological tumor， and so on. Patriniae Herba is often used in the clinical treatment of colorectal cancer， but its mechanism of action is not clear. Modern studies have found that Patriniae Herba contains triterpenoids， saponins， iridoids， flavonoids， and other chemical components， with antioxidant， anti-tumor， anti-bacterial， and other pharmacological effects. The main anti-tumor components of Patriniae Herba are flavonoids. The analysis of network pharmacology and the spectrum-effect relationship has suggested that quercetin， luteolin， apigenin， isoorientin， and isovitexin play a major role in inhibiting the occurrence and development of colorectal cancer. In vivo and in vitro studies have shown that flavonoids in Patriniae Herba can play an anti-tumor role in various ways， such as preventing precancerous lesions of colorectal cancer， inhibiting the growth and proliferation of cancer cells， blocking cancer cell cycle， promoting cancer cell apoptosis， and reversing drug resistance of colorectal cancer. The oral availability of flavonoids is low. The gut is the main metabolic site of flavonoids in the body， its metabolic pathway is closely related to gut microbiota. This paper reviewed the anti-tumor mechanism of flavonoids and their influence on gut microbiota to provide a reference for further research on the mechanism of Patriniae Herba against colorectal cancer and its clinical application.

Effect of Salvianolic Acid B Combined with Puerarin on Pyroptosis of SH-SY5Y Cells Injured by Oxygen-glucose Deprivation/Reoxygenation / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of salvianolic acid B combined with puerarin in protecting the SH-SY5Y cells from the damage by oxygen-glucose deprivation/reoxygenation （OGD/R） based on pyroptosis. MethodSH-SY5Y cells were used to establish the model of OGD/R， and cells were classified into the control， OGD/R， 10 μmol·L-1 salvianolic acid B， 100 μmol·L-1 puerarin， 10 μmol·L-1 salvianolic acid B + 100 μmol·L-1 puerarin， and 10 μmol·L-1 NOD-like receptor protein 3 （NLRP3） inhibitor MCC950 groups. Except the control group， other groups were rapidly reoxygenated for 12 h after 6 h OGD for modeling. The cell survival rate was determined by the methyl thiazolyl tetrazolium （MTT） assay. An optical microscope was used to observe the cell morphology. A spectrophotometer was used to determine the content of lactic dehydrogenase （LDH） in culture supernatant. Cell damage was measured by Hoechst/PI staining. The mRNA levels of NLRP3， cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β） were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein activation of Caspase-1 and NLRP3 was detected by immunofluorescence. Western blot was employed to determine the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1. ResultCompared with the control group， the OGD/R group showed decreased cell survival rate （P<0.01）， damaged cell morphology， increased leakage rate of LDH （P<0.01）， up-regulated mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.01）， and up-regulated protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.01）. Compared with the OGD/R group， salvianolic acid B， puerarin， and salvianolic acid B combined with puerarin improved cell survival rate （P<0.01）， and the combined treatment group outperformed salvianolic acid B and puerarin used alone （P<0.01）. Salvianolic acid B combined with puerarin and MCC950 both improved cell morphology， reduced the leakage of LDH （P<0.01）， alleviated cell damage， and down-regulated the mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.05， P<0.01） and also the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.05， P<0.01）. ConclusionThe results indicated that salvianolic acid B combined with puerarin can alleviate the OGD/R-induced damage of SH-SY5Y cells by inhibiting pyroptosis.

Randomized Controlled Trial of Anti-reflux Mucosectomy Versus Radiofrequency Energy Delivery for Proton Pump Inhibitor-refractory Gastroesophageal Reflux Disease

Background/Aims@#The efficacy and safety of anti-reflux mucosectomy (ARMS) or radiofrequency energy delivery in the treatment of gastroesophageal reflux disease (GERD) have been reported, but the difference between the 2 remains unclear. @*Methods@#This was a single center, randomized, comparative clinical study. Patients with symptoms of heartburn and/or regurgitation despite proton pump inhibitor treatment were randomly assigned to either ARMS group (n = 20) or radiofrequency group (n = 20).Primary outcome was the standardized GERD questionnaire (GERDQ) at 2 years after the procedures. Secondary outcomes were the proportions of patients with complete proton pump inhibitor (PPI) cessation and patients satisfied with the treatment. @*Results@#A total of 18 patients randomized to ARMS and 16 to radiofrequency were analyzed in this study. The operation success rate of the 2 groups was 100%. In both ARMS and radiofrequency groups, GERDQ scores at 2 years after the procedures were significantly lower than that before operation (P = 0.044 and P = 0.046). At 2 years postoperatively, the scores of GERDQ did not differ between the 2 groups (P = 0.755). There was no significant difference in the rate of discontinuation of PPIs and patient satisfaction in the ARMS and radiofrequency groups (P = 0.642 and P = 0.934). @*Conclusions@#The clinical efficacy of ARMS and radiofrequency for the PPI-refractory GERD is equivalent. ARMS, the efficacy of which could be maintained for at least 2 years, is promising endoscopic management for the treatment of refractory GERD.

Norepinephrine/β2 -Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer / 한국유방암학회지

Purpose@#Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. @*Methods@#The expression levels of the β2 -adrenergic receptor (β2 -AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2 -AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2 -AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. @*Results@#The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2 -AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the coculture assay, the sympathetic adrenergic NE/β2 -AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. @*Conclusion@#These results suggest that NE/β2 -AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

Experimental study on the therapeutic effect of different bleaching methods on white-spot lesions of the enamel using optical coherence tomography / 口腔医学

Objective@#To investigate the efficacy of different bleaching methods on white-spot lesions of the enamel using optical coherence tomography and to evaluate its feasibility for monitoring the therapeutic effects on white-spot lesions. @*Methods@#Forty-eight sound premolars extracted for orthodontic reasons were selected and cut for 4 mm×4 mm×2 mm enamel blocks in buccal surfaces of the crowns. The samples were covered with acid-resistant varnish (except for the buccal surfaces) and immersed in demineralization solution for 18 days to establish the white-spot lesion models of the enamels. Samples were randomly divided into four groups (n=12). Group A was given demineralization only. Specimens in Group B, C and D were treated with 40% hydrogen peroxide, resin infiltration and 40% hydrogen peroxide combined with resin infiltration, respectively. Eight samples in each group were randomly selected. OCT was applied to observe the optical changes of the enamel surface and according to the OCT scanning results, the demineralization depth of enamel samples in each group was calculated. Then, the enamel blocks were embedded in epoxy resins, except the buccal surfaces, and measured for the microhardness values of the enamel surface by a microindentation hardness tester. Four samples in each group were cut longitudinally, and the ultrastructural changes of enamel samples in each group were observed by scanning electron microscope. @* Results@#OCT showed that the light scattering characteristics of enamel surface changed in all groups, and the bright layer was formed, but the thickness of bright layer in Group C and D was significantly lower than that in Group A and B (P<0.05). The microhardness values (kg/mm2) of the samples in Group A-D were (214.99±31.70), (250.66±33.64), (312.42±18.01) and(286.53±26.65), respectively. The microhardness of enamel surfaces in Group C and D was significantly higher than that in Group A and B (P<0.05), and the ultrastructure of enamel surfaces in Group C and D were more flat and dense in SEM observation (P<0.05). @*Conclusion@#The methods of resin infiltration therapy or 40% hydrogen peroxide combined with resin infiltration could effectively improve white-spot lesions of the enamel and the non-invasive OCT can be used as a better evaluation method for the diagnosis and treatment of white-spot lesions of the enamel.

Pollution characteristics, long-term variation trend, and health risk assessment of lead in ambient PM2.5 in Jinan / 环境与职业医学

Background A number of studies have shown that heavy metals in atmospheric PM2.5 have impacts on human health, while studies on the impact of long-term and low-concentration exposure to lead in PM2.5 on human health are limited. Objective To investigate the pollution characteristics of lead in ambient PM2.5 and assess its chronic health risks. Methods Daily PM2.5 concentration data in Jinan from 2014 to 2019 were collected, and the year-by-year trend of PM2.5 concentration was analyzed. Licheng District (an industrial area) and Shizhong District (a residential area) were elected to install an ambient PM2.5 monitoring stationrespectively. The sampling instrument was a 100 L·min−1 high-flow PM2.5 sampler, with a cumulative sampling time of 20-24 h per day, using a quartz fiber filter membrane for lead detection and a glass fiber filter membrane for PM2.5 determination. The sampling frequency was 7 consecutive days per month from the 10th to the 16th (A total of 493 d were sampled and some were missing; 172 d during the heating period and 321 d during the non-heating period). Two PM2.5 samples were collected in one monitoring site each day. A total of 986 samples were collected in one monitoring site. The lead content in PM2.5 samples was detected by inductively coupled plasma mass spectrometry. The concentration of PM2.5 was measured by weighing method. The annual average concentration and enrichment factor of lead in PM2.5, the change trend of lead content per unit mass of PM2.5, and the difference between heating period and non-heating period from 2014 to 2019 were estimated. Technical guide for environment health risk assessment of chemical exposure (WS/T 777-2021) was used to assess the health risks of exposure to lead in PM2.5. Results The average annual concentration of lead in PM2.5 ranged from 23.2 ng·m−3 to 154.7 ng·m−3. The average concentration in heating period from 2015 to 2019 was higher than that in non-heating period, and the differences in 2015, 2017, and 2019 were statistically significant (P < 0.01 or 0.001). The enrichment factors ranged from 200 to 1342 in 2014 to 2019. The average enrichment factors in heating period in 2015, 2017, and 2018 was higher than those in non-heating period, and the difference was statistically significant (P < 0.05 or 0.001). The lead contents per unit mass of PM2.5 ranged from 493 ng·mg−1 to 1944 ng·mg−1, and the differences between heating period and non-heating period in 2014, 2017, and 2018 were statistically significant (P < 0.05 or 0.001). The average annual concentration and enrichment factor of lead in PM2.5 showed a downward trend, and thus the lead content per unit mass of PM2.5 also decreased. From 2014 to 2019, the carcinogenic risk of lead in PM2.5 in Jinan ranged from 1.69×10−8 to 2.45×10−6, showing a significant downward trend year by year, and the 95th percentile decreased by 3%-46% from the previous year. The carcinogenic risk level of lead was reduced to an acceptable level (<1×10−6) after 2017. Conclusion From 2015 to 2019, lead concentration and enrichment factor in PM2.5 increase during heating period compared with non-heating period, but it is not completely consistent of lead content in PM2.5 per unit mass. From 2014 to 2016, exposure to lead in PM2.5 may elevate carcinogenic risk to human. After 2017, the carcinogenic risks of exposure to lead in PM2.5 are at an acceptable level.

Willingness and influencing factors for cervical cancer screening among women in Chizhou / 公共卫生与预防医学

Objective To investigate the influencing factors of willingness to screen for cervical cancer in women in Chizhou. Methods A cross-sectional web-based survey of 3,058 migrant women living in Chizhou was conducted through a social media platform. The survey included questionnaires on socioeconomic characteristics, history of cervical cancer screening, knowledge of cervical cancer prevention and treatment, and attitude. The χ2 test and logistic regression were used to analyze the influencing factors of willingness to screen. Results Under 60 years of age, having a spouse or sexual partner (OR=1.368), having a junior high school education or above, living in urban areas (OR = 1.501), local household registration (OR=1.363), high monthly income, and high knowledge of cervical cancer prevention and control (OR=1.198) were positively associated with the rate of willingness to undergo cervical screening. Among attitude barriers, there were statistically significant differences in fear of seeing male doctors (38.23%), fear of seeing poor results (31.92%), belief that screening was painful (23.56%), shyness or embarrassment (20.18%), and belief that they did not need to participate in screening due to asymptomatic (17.56%), having received HPV vaccine (15.86%), or ages at which screening was not considered necessary (15.14%) between the groups (P<0.05). Conclusion Socioeconomic characteristics, knowledge of prevention and treatment, fear of screening experience, and lack of motivation are related factors affecting cervical cancer screening willingness. Achieving cervical cancer elimination requires action to improve screening coverage in socio-economic, health education and women's attitudes.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Baicalin inhibits PDK1 to mediate glucose metabolism reprogramming and intervene rheumatoid arthritis synovial inflammation / 药学学报

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Effect of asiaticoside on OGD/R induced injury of H9C2 cardiomyocytes based on PI3K/Akt/Beclin-1 signaling pathway / 药学学报

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

The coronary heart disease of phlegm-stasis cementation syndrome in mini-swine based on platelet proteomics / 药学学报

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor drugs for the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P&#x003C;0.05), the CMT in both groups was lower than that before the treatment(P&#x003C;0.05), and the improvement of CMT of the combination group was better than the injection group(-155.93±143.79μm vs. -95.36±56.81μm, P&#x003C;0.05). After 3mo of treatment, each kinds of TCM syndrome in the combination group were significantly improved compared with those syndromes before the treatment(P&#x003C;0.001). In the injection group, only blurred vision was improved(P&#x003C;0.05). After the treatment, the scores of dizziness and insomnia, soreness and weakness of waist and knees, paleness and cold limbs, dry eyes and fatigue in the combination group were significantly lower than the injection group(P&#x003C;0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.