Preparation and cytotoxicity of doxorubicin-containing gold nanoparticles / 药学实践与服务

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.

Content measurement of doxorubicin hydrochloride and lonidamine by HPLC / 药学实践与服务

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Effect of different temperature lavage fluid on shivering and inflammatory response after ureteral holmium laser lithotripsy / 国际外科学杂志

Objective:To investigate the effects of constant body temperature (37 ℃), constant room temperature (24 ℃) and cold liquid (20 ℃) on shivering and inflammatory response after holmium laser lithotripsy under ureteroscope.Methods:A total of 132 patients receiving holmium laser lithotripsia under ureteroscope treated in the Second People′s Hospital of Lianyungang City from July 2020 to July 2023 were selected as the study objects. According to the intraoperative lavage fluid temperature, they were divided into cold liquid group (20 ℃, n=44), equal room temperature group (24 ℃, n=44) and equal body temperature group (37 ℃, n=44).. Anova was used to compare the occurrence of postoperative chills in the three groups at 10 min, 30 min, immediately after the operation, and the anti-inflammatory response of stress before and after the operation. Chi-square test was used to compare the occurrence of postoperative chills. Results:The difference of core body temperature between the three groups at 10 min, 30 min and immediately after operation was statistically significant. The core body temperature of the cold liquid group was lower than that of the equal room temperature group and the equal body temperature group at the above time point ( P<0.05). There was no significant difference in core body temperature between the isoroom temperature group and the isobody temperature group at 10 min, 30 min and immediately after operation ( P>0.05)..The levels of norepinephrine and serum cortisol in the three groups were higher after surgery than before surgery, and the levels in the cold liquid group were higher than those in the isothermal group and the isothermal group ( P<0.05), but there was no statistical significance between the isothermal group and the isothermal group ( P>0.05).The levels of C-reactive protein, interleukin-10 and white blood cells were higher after operation than before operation, but there was no statistical significance among the three groups ( P>0.05).There was a statistically significant difference in the incidence of postoperative chills among the three groups ( χ2=6.87, P=0.03). Nine cases of postoperative chills occurred in the cold body fluid group, the highest incidence of chills was 20.45%, 3 cases occurred in the room temperature group, and 2 cases occurred in the body temperature group. There was no significant difference in the incidence of chills (6.81% vs 4.55%) ( P>0.05). Conclusion:In holmium laser lithotripsy under ureteroscope, compared with cold liquid lavage, intraoperative equi-room temperature lavage and equi-body temperature lavage can maintain constant intraoperative body temperature, relieve stress reaction, reduce postoperative inflammatory reaction and lower incidence of postoperative chills.

Clinical study of electroacupuncture plus stuck-needle lifting method for intractable facial paralysis / 针灸推拿医学（英文版）

Objective:To observe the efficacy of using electroacupuncture(EA)plus stuck-needle lifting method to treat intractable facial paralysis based on the myofascial theory. Methods:Ninety patients with intractable facial paralysis were divided into a control group and an observation group using the random number table method,with 45 cases in each group.The control group was given conventional EA treatment,and the observation group received EA plus the stuck-needle lifting method based on the myofascial theory for 4 consecutive weeks,6 sessions each week.The electromyographic results,modified Portmann scale(MPS)score,facial nerve function index(FNFI),and total effective rate were compared. Results:There were no significant differences in the MPS and FNFI scores between the two groups before treatment(P>0.05).After treatment,the total effective rate and FNFI and MPS scores were notably higher in the observation group than in the control group(P<0.05).There were no significant differences in the electromyographic readings between the two groups before the intervention(P>0.05).After the intervention,the observation group had a shorter blink reflex R1 latency and a higher facial nerve compound muscle action potential compared with the control group,and the between-group differences were statistically significant(P<0.05). Conclusion:EA plus stuck-needle lifting method based on the myofascial theory can enhance treatment efficacy for intractable facial paralysis.

Huanglian Jiedutang Regulates HIF-1α/VEGF Signaling Pathway to Improve Learning and Memory Abilities of APP/PS1 Transgenic Mice / 中国实验方剂学杂志

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg-1·d-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg-1·d-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.

Licochalcone A induces cell cycle arrest in human lung squamous carcinoma cells via the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism.@*METHODS@#MTT assay was used to detect the changes in proliferation of H226 cells after treatment with different concentrations of LCA for 48 h, and the IC50 of LCA was calculated. Flow cytometry was used to analyze cell cycle changes in H226 cells treated with 10, 20, and 40 μmol/L LCA, and the expressions of cyclin D1, cyclin-dependent kinase CDK2 and CDK4, and p-PI3K, PI3K, p-Akt, and Akt in the treated cells were detected using Western blotting. The effect of intraperitoneal injection of LCA for 24 days on tumor volume and weight was assessed in a BALB/c-nu mouse model bearing lung squamous carcinoma xenografts.@*RESULTS@#MTT assay showed that LCA significantly decreased the viability of H226 cells with an IC50 of 28.3 μmol/L at 48 h. Flow cytometry suggested that LCA treatment induced obvious cell cycle arrest at the G1 phase. LCA treatment also significantly decreased the expressions of cyclin D1, CDK2, and CDK4, and inhibited the phosphorylation of PI3K and Akt in H226 cells. In the tumor-bearing mice, LCA treatment for 24 days significantly reduced the tumor volume and weight.@*CONCLUSION@#LCA is capable of inhibiting the proliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.

Retrospective Study of The Outcome of Primary Repair of Arteriovenous Fistula (AVF) Aneurysm and Pseudoaneurysm in Secondary Hospital Setting (Kajian Retrospektif Pembaikian Primer Ateriovenous Fistula (AVF) Aneurisma dan Pseudoaneurisma di Hospital Sekunder) / Jurnal Sains Kesihatan Malaysia

@#Aneurysms and pseudoaneurysm are commonly encountered with arteriovenous vascular access for haemodialysis. They are difficult complications to manage. Due to the limited number of vascular centers available, patients were unable to seek treatment until further complications arise. The technique of partial aneurysmectomy and primary repair was adopted as the method of repair in this study. A total of 20 cases underwent the surgery from 2019 to 2020. Among the 20 cases, one patient had two pseudoaneurysms at different location which requires her to undergo the procedure twice. The successful cannulation rate post repair was 70% whereas the overall complication rate was 35% which might be attributed to the small sample size. Overall, this study demonstrated that AVF aneurysm and pseudoaneurysm can be safely treated with this approach and can be done effectively in non-vascular centers by general surgeons.

Correlation analysis of asthma and prognosis in 148 children with low immune function / 公共卫生与预防医学

Objective To analyze the effect of immune function on the condition and prognosis of asthma in children with asthma. Methods A total of 148 children with asthma diagnosed in Qinghai women and children's Hospital from January 2018 to January 2021 were included in the analysis, the immune function of the children was determined, and the information of all children was followed up for 6 months after treatment; compared The condition and follow-up prognosis of children with immunocompromised and normal immune function were analyzed and discussed, and the correlation between the expression levels of immunoglobulins (IgG, IgA, IgM) and the condition and short-term recurrence prognosis (6 months) of children was analyzed and discussed, so as to guide Prevention and clinical work. Statistical analysis was done using SPSS19.0. Results The average age of 148 children with recurrent respiratory tract infection in the study was (8.94±3.65) years old, including 70 male children. The condition of the children was evaluated and classified into mild/severe cases: 148 children in this study included mild cases. There were 98 cases and 50 severe cases. There were more males and lower BMI levels in severe children (P<0.05) . The levels of IgG, IgA and IgM in children were all lower in severe children (P<0.05) . The follow-up found that the proportion of relapses in critically ill children was higher (P<0.05). Comparing the levels of IgG, IgA, and IgM in mild and severe children, the average levels of IgG, IgA, and IgM in severe children were lower than those in the mild group, and the difference was statistically significant (P<0.05); recurrence within 6 months of follow-up Prognostic evaluation showed that 19 of the 148 children had relapse, and the levels of IgG, IgA, and IgM in severe relapsed children were significantly lower than those without relapse (P<0.05). Analysis of the relevant factors potentially affecting the prognosis of recurrence showed that gender (female) (OR=1.726) , BMI level (weight loss) (OR=1.613) , IgG expression level factor (low expression) (OR=1.898) , IgA expression Level factor (low expression) (OR=3.509) , IgM expression level factor (low expression) (OR=3.217) and disease factor (severe) (OR=3.619) were potential risk factors, which would increase the risk of poor prognosis. Conclusion The asthma attack in children with immunocompromised immune function is relatively severe, and the short-term recurrence probability is higher, which deserves clinical attention and preventive intervention.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Effects of tumor necrosis factor-alpha/extracellular signal-regulated kinase pathway on migration ability of HaCaT cells and full-thickness skin defects in mice / 中华烧伤杂志

Objective: To investigate the effects of tumor necrosis factor-alpha (TNF-α)/extracellular signal-regulated kinase (ERK) pathway on the migration ability of HaCaT cells and full-thickness skin defects in mice. Methods: The experimental research method was adopted. According to the random number table (the same below), HaCaT cells were divided into the normal oxygen group and the hypoxia group cultured under hypoxia (with oxygen volume fraction of 1%, the same below) condition. After 24 hours of culture, the significantly differentially expressed genes between the 2 groups were screened using the microarray confidence analysis software SAM4.01. The significance of the number of each gene in the signaling pathway was analyzed through the Kyoto encyclopedia of genes and genomes to screen the significantly differentially signaling pathways (n=3). HaCaT cells were cultured for 0 (immediately), 3, 6, 12, and 24 h under hypoxia condition. The secretion level of TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 5. HaCaT cells were divided into normal oxygen group, hypoxia alone group, and hypoxia+inhibitor group cultured with FR180204 (an ERK inhibitor) and under hypoxia condition. The cells were cultured for 3, 6, 12, and 24 h. The migration ability of the cells was detected by scratch test (n=12). The expressions of phosphorylated nuclear factor kappa B (p-NF-κB), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), N-cadherin, and E-cadherin in HaCaT cells were detected by Western blotting under hypoxic condition for 0, 3, 6, 12, and 24 h (n=3). Sixty-four BALB/c male mice aged 6 to 8 weeks were used to make a full-thickness skin defect wound model on the dorsum of the mice. The mice were divided into the blank control group and the inhibitor group treated with FR180204, with 32 mice in each group being treated accordingly. On post injury day (PID) 0, 3, 6, 9, 12, and 15, the wound conditions of mice were observed and the healing rate was calculated (n=8). On PID 1, 3, 6, and 15, hematoxylin-eosin staining was used to observe neovascularization, inflammatory cell infiltration, and epidermal regeneration on wound, Masson staining was used to observe collagen deposition on wound, the expressions of p-NF-κB, p-p38, p-ERK12, N-cadherin, and E-cadherin in wound tissue were detected by Western blotting (n=6), the number of Ki67 positive cells and the absorbance value of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry (n=5), the protein expressions of interleukin 6 (IL-6), IL-10, IL-1β, and CCL20 in wound tissue were detected by ELISA (n=6). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, factorial design analysis of variance, Tukey test, least significant difference test, and independent sample t test. Results: After 24 hours of culture, compared with normal oxygen group, 7 667 genes were up-regulated and 7 174 genes were down-regulated in cells in hypoxic group. Among the above differentially expressed genes, the TNF-α signaling pathway had significant change (P<0.05) with large number of genes. Under hypoxia condition, the expression of TNF-α at 24 h of cell culture was (11.1±2.1) pg/mL, which was significantly higher than (1.9±0.3) pg/mL at 0 h (P<0.05). Compared with normal oxygen group, the migration ability of cells in hypoxia alone group was significantly enhanced at 6, 12, and 24 h of cell culture (with t values of 2.27, 4.65, and 4.67, respectively, P<0.05). Compared with hypoxia alone group, the migration ability of cells in hypoxia+inhibitor group was significantly decreased at 3, 6, 12, and 24 h of cell culture (with t values of 2.43, 3.06, 4.62, and 8.14, respectively, P<0.05). Under hypoxia condition, the expressions of p-NF-κB, p-ERK1/2, and N-cadherin were increased significantly at 12 and 24 h of cell culture compared with 0 h of culture (P<0.05), the expression of p-p38 was significantly increased at 3, 6, 12, and 24 h of cell culture (P<0.05), the expression of E-cadherin was significantly decreased at 6, 12, and 24 h of cell culture (P<0.05), the expression of p-ERK1/2, p-NF-κB, and E-cadherin was time-dependent. Compared with blank control group, on PID 3, 6, 9, 12, and 15, the wound healing rate of mice in inhibitor group was significantly decreased (P<0.05); there were more inflammatory cell infiltration around the wound edge of mice in inhibitor group on PID 3, 6, and 15, especially on PID 15, a large number of tissue necrosis and discontinuous new epidermal layer were observed on the wound surface, and collagen synthesis and new blood vessels were reduced; the expression of p-NF-κB in the wound of mice in inhibitor group was significantly decreased on PID 3 and 6 (with t values of 3.26 and 4.26, respectively, P<0.05) but significantly increased on PID 15 (t=3.25, P<0.05), the expressions of p-p38 and N-cadherin were significantly decreased on PID 1, 3, and 6 (with t values of 4.89, 2.98, 3.98, 9.51, 11.69, and 4.10, respectively, P<0.05), the expression of p-ERK1/2 was significantly decreased on PID 1, 3, 6, and 15 (with t values of 26.69, 3.63, 5.12, and 5.14, respectively, P<0.05), the expression of E-cadherin was significantly decreased on PID 1 (t=20.67, P<0.05) but significantly increased on PID 6 (t=2.90, P<0.05); the number of Ki67 positive cells and absorbance value of VEGF of wound in inhibitor group were significantly decreased on PID 3, 6, and 15 (with t values of 4.20, 7.35, 3.34, 4.14, 3.20, and 3.73, respectively, P<0.05); the expression of IL-10 in the wound tissue of the inhibitor group was significantly decreased on PID 6 (t=2.92, P<0.05), the expression of IL-6 was significantly increased on PID 6 (t=2.73, P<0.05), the expression of IL-1β was significantly increased on PID 15 (t=3.46, P<0.05), and CCL20 expression levels were significantly decreased on PID 1 and 6 (with t values of 3.96 and 2.63, respectively, P<0.05) but significantly increased on PID 15 (t=3.68, P<0.05). Conclusions: The TNF-α/ERK pathway can promote the migration of HaCaT cells, and regulate the healing of full-thickness skin defect wounds in mice by affecting the expression of inflammatory cytokines and chemokines.

Studies on orally disintegrating tablet of diphenhydramine hydrochloride and caffeine / 药学实践与服务

Objective To optimize the formulation and preparation of diphenhydramine hydrochloride and caffeine orally disintegrating tablet. Methods Melt granulation technology of steric acid and API was used to mask the unpleasant tasting of diphenhydramine hydrochloride. The tablets were prepared by direct pressing the dry powder with CCMC-Na as disintegrating agent. The formulation was optimized by orthogonal experiments to achieve the shortest disintegration time and the best taste correction. Results The optimized formula of orally disintegrating tablet was as follows： diphenhydramine hydrochloride 25 mg, caffeine 60 mg, stearic acid 25 mg, aspatan 40 mg, blueberry essence 7 mg, mannitol 45 mg, MCC 210 mg, CCMC-NA 25 mg, SDS 8 mg and magnesium stearate 5 mg. Conclusion This preparation method for orally disintegrating tablet of diphenhydramine hydrochloride and caffeine is practical and easy for quality control.

Establishment of determination of tetrodotoxin sustained-release microspheres / 药学实践与服务

Objective To establish a detection method for the determination of tetrodotoxin (TTX) in sustained-release microspheres. Methods The HPLC separation of tetrodotoxin was performed on an Agilent ZORBAX SB-C18 column (4.6mm×150mm,5 μm) with acetonitrile, 8mmol/L sodium heptane sulfonate containing 0.005% TFA (5:95) (pH 4.0) as the mobile phase. The flow rate was 1.0 ml/min. The UV detection wavelength was 200 nm and the column temperature was 30 °C. Results The method had good specificity and linearity of TTX in the concentration range of 1−20 μg/ml. The intra-day precision, inter-day precision, stability and repeatability of the method were good, and the average recoveries were found between 98.0% and 102.0%. Conclusion This study established an HPLC method which was suitable for the determination of tetrodotoxin sustained-release microspheres. The method is accurate and reliable within the applicable range, with strong specificity, which could lead to quantitative detection.

Advances in medicinal research on tetrodotoxin / 药学实践与服务

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine organisms. It has been used as an inhibitor of voltage-gated sodium channels (VGSCs), which could selectively bind to the α-subunit on the outer vestibule of VGSCs, preventing sodium ions from entering the channel, resulting in pharmacological activities. As a typical sodium channel blocker, TTX shows a significant analgesic effect. TTX could selectively block Na+ channels without affecting other ion channels, therefore it could reduce the probability of adverse reactions caused by commonly used antiarrhythmic drugs. In addition, TTX has a significant role in detoxification and prevention of renal failure, so TTX has great potential as a medicine. The structure and physicochemical properties, mechanism of action, pharmacological activities and preparations of tetrodotoxin have been reviewed in this paper, so as to provide a general support for the evaluation of its druggability and application in the field of pharmacy.

Establishment and validation of a predictive model for degenerative lumbar disc disease in young and middle-aged people / 解放军医学杂志

Objective To establish and validate the nomogram prediction model of degenerative lumbar disc disease in young and middle-aged people.Methods From January 2020 to March 2022,232 young and middle-aged people who were examined with MRI of lumbar intervertebral disc and standard standing position lumbar anteroposterior and lateral X-ray films in Suzhou Ninth Hospital Affiliated to Soochow University were selected as the study subjects.Collecting the factors that may affect the occurrence of degenerative lumbar disc disease in young and middle-aged people,the people were divided into degenerative disease group(n=78)and non-degenerative disease group(n=154)according to the presence or absence of degenerative lumbar disc disease.Influencing factors were compared between the two groups,the independent influencing factors screened out by multifactor logistic regression,the nomograph model was constructed by R software,and the model verified.Results Among 232 young and middle-aged people included in this study,78(33.6%)had degenerative lumbar disc diseases.The results of multivariate logistic regression analysis showed that the increase of BMI,sedentariness,the increase of IL-1β level were the risk factors of degenerative lumbar disc disease in young and middle-aged people;the increase of pelvic incidence angle and the increase of miRNA-142-3p level were protective factors for degenerative lumbar disc disease in young and middle-aged people(P<0.05).The nomogram model was constructed according to the results of multifactor analysis.ROC results showed that AUC was 0.889(95%CI 0.844-0.933,P<0.05),the average absolute error of internal validation was 0.017,the prediction curve was basically fitted with the standard curve,and the H-L goodness of fit test showed that the model was consistent(P>0.05).The decision curve shows that the clinical benefit rate is the highest when the model prediction probability threshold is 0.16-0.80.Conclusions Degenerative lumbar disc disease in young and middle-aged people is affected by such factors as BMI,sedentariness,and incidence angle of pelvis,and the nomogram model established based on this has high differentiation and accuracy of prediction.

CT quantitative analysis of functional small airway and pulmonary vascular in imaging phenotypes of chronic obstructive pulmonary disease / 中华放射学杂志

Objective:To explore the differences of functional small airway and pulmonary vascular parameters in chronic obstructive pulmonary disease (COPD) of different imaging phenotypes.Methods:One hundred and thirty COPD patients underwent biphasic CT scanning in Shanghai Changzheng Hospital from August 2018 to August 2020 were analyzed retrospectively. The patients were classified into three phenotypes based on the presence of emphysema and bronchial wall thickening on CT images. Phenotype A: no emphysema or mild emphysema, with or without bronchial wall thickening; Phenotype E: obvious emphysema without bronchial wall thickening; phenotype M: significant emphysema and bronchial wall thickening were present. Parametric response map (PRM) and pulmonary vascular parameters were quantitatively measured at the whole lung level. PRM parameters included the volume of emphysema (PRMV Emphysema), the volume of functional small airway (PRMV fSAD), the volume of normal pulmonary parenchyma (PRMV Normal) and its volume percentage (%). Pulmonary vascular parameters included the number of vessels (N) and cross-sectional area vessels<5 mm 2 (N -CSA<5) at 6, 9, 12, 15, 18 21, 24 mm distance from the pleura. ANOVA or Kruskal-Wallis H tests were used to compare the differences for PRM and pulmonary vascular parameters among the three phenotypes, and LSD or Bonferroni tests were used for multiple comparisons. Results:There were significant differences among the three phenotypes for PRMV fSAD, PRMV Emphysema, PRMV fSAD%, PRMV Emphysema%, and PRMV Normal% at the whole lung level ( P<0.05). PRMV Emphysema, PRMV Emphysema%, PRMV Fsad, PRMV fSAD% of phenotype A were lower than those of phenotype E and M ( P<0.001), while there was no significant difference for PRMV Emphysema, PRMV Emphysema%, PRMV fSAD, PRMV fSAD% between phenotype E and phenotype M ( P>0.05). There were significant differences in N and N -CSA<5 that 6 mm distance from the pleura among the three groups( P<0.05). Among them, N and N -CSA<5 that 6 mm distance from pleura in phenotype M were significantly lower than those in phenotype A( P<0.001,0.002); No significant differences was found in N between phenotype M and phenotype E( P>0.05), while there was significant differences in N -CSA<5 between phenotype M and phenotype E( P=0.034). Conclusion:Biphasic quantitative CT analysis can reflect the heterogeneity of the functional small airways and pulmonary vascular abnormality in COPD with different phenotypes, and provide objective evidence for individualized diagnosis and treatment.

The impact of flash glucose monitoring on glycemic control, residual islet function, and patient-reported outcomes in children and adolescents with newly diagnosed type 1 diabetes / 中国医师杂志

Objective:To assess the effect of flash glucose monitoring (FGM) compared with self-monitoring of blood glucose (SMBG) on glycemic control, residual islet function, and patient-reported outcomes in children and adolescents with newly diagnosed type 1 diabetes within 1 year.Methods:133 children and adolescents with newly diagnosed T1DM in the T1D clinic of the Second Xiangya Hospital of Central South University from January 2016 to January 2020 were divided into two groups: FGM group ( n=82) and SMBG group ( n=51). The observation indexes included hemoglobin A1c (HbA 1c), fasting and postprandial blood glucose (FBG and 2 h BG), C-peptide (FCP and 2 h CP) during the one-year follow-up, Δ CP (2 h CP-FCP), patient-reported hypoglycemia and questionnaires regarding self-management of diabetes and quality of life. Results:At 6 months, HbA 1c in 2 groups was significantly decreased (all P<0.05); at 6 to 12 months, HbA 1c in FGM group tended to be stable ( P>0.05); at 12 months, HbA 1c in SMBG group was significantly increased compared with 6 months ( P=0.001). At 12 months, HbA 1c in SMBG group was higher than that in FGM group ( P=0.001). At 12 months, FBG in FGM group was equivalent to the baseline level ( P>0.05), while FBG in SMBG group was significantly higher than the baseline level ( P=0.006). 2 h BG only decreased at the 6th and 12th month in FGM group (all P<0.05). The FCP of SMBG group was significantly decreased at 12 months ( P<0.05), and the 2 h CP, Δ CP in the two groups decreased gradually (all P<0.05). FGM group had more hypoglycemic events at 6 and 12 months (all P<0.05). At 6 months, the score of Self-Management of T1D for Adolescents (SMOD-A) in FGM group was significantly improved ( P=0.001). During the follow-up period, the quality of life score of FGM group was stable ( P>0.05), while the quality of life score of SMBG group had a downward trend ( P=0.052). Conclusions:In newly diagnosed children and adolescents with T1DM, early application of FGM for blood glucose management will help to improve HbA 1c and reduce postprandial blood glucose. In addition, the self-management ability of children with FGM was improved after 6 months.

Value of CT pulmonary vascular quantitative parameters in diagnosis of chronic obstructive pulmonary disease patients and high-risk groups / 中华放射学杂志

Objective:To explore the diagnostic value of CT pulmonary vascular quantitative parameters in patients with chronic obstructive pulmonary disease (COPD) and high-risk groups.Methods:A retrospective study of 1 126 patients who underwent chest CT examination and pulmonary function test in Shanghai Tongji Hospital from January 2015 to August 2020. According to lung function, they were divided into COPD group (471 cases), high-risk group (454 cases), and normal control group (201 cases). Pulmonary vascular parameters on chest CT, including the total number of vessels (N total), the number cross-sectional area of vessels under 5 mm 2 (N CSA<5), lung surface area (LSA), number of pulmonary blood vessels per unit lung surface area (N total/LSA) and the total area of vessels (VA total) at a 9, 15, 21 mm depth from the pleural surface, and the total blood vessel volume (TBV), blood vessel volume under 5 mm 2 and 10 mm 2(BV5 and BV10) were measured quantitatively. Kruskal-Wallis H test was used to compare the differences of quantitative parameters of pulmonary vascular in the three groups; Spearman rank test was used to analyze the correlation between CT pulmonary vascular parameters and pulmonary function. Results:There were significant differences in N total/LSA at a 9, 15, 21 mm depth from the pleural surface among three groups ( P<0.05). There were significant differences in N CSA<5, N total at a 9 mm depth from the pleural surface among three groups ( P<0.05). There were significant differences in LSA at a 9 mm depth from the pleural surface, N CSA<5, N total, LSA, VA total at a 15, 21 mm depth from the pleural surface and TBV, BV5 and BV10 among three groups ( P<0.05). In high-risk group, there were positive correlation between N total/LSA, VA total at a 9 mm depth from the pleural surface and some pulmonary function parameters ( r=0.095-0.139, P<0.05). N CSA<5, N total, LSA, N total/LSA, TBV, BV5 and BV10 at different depth from pleural surface were negatively correlated with some pulmonary function parameters ( r=-0.110--0.215, P<0.05). In COPD group, number of vessels at a 9 mm depth from the pleural surface was positively correlated with the diffusion capacity for carbon monoxide of the lung single breath ( r=0.105, 0.103, P<0.05). In addition to N total/LSA were positively correlated with lung function parameters ( r=0.181-0.324, P<0.05), the remaining pulmonary vascular parameters were negatively correlated with some pulmonary function parameters ( r=-0.092--0.431, P<0.05). Conclusion:Quantitative chest CT imaging are able to effectively evaluate pulmonary vascular changes in COPD patients and high-risk groups, and the quantitative parameters of pulmonary vascular CT may distinguish COPD from high-risk groups, providing a novel means for early diagnosis of COPD and prediction of high-risk groups.

Construction of a prediction model for lung cancer combined with chronic obstructive pulmonary disease by combining CT imaging features with clinical features and evaluation of its efficacy / 中华放射学杂志

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

Frailty evaluation and risk factors for older patients with comorbidities: a cross-sectional study / 中华老年医学杂志

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Licochalcone A inhibits osteosarcoma proliferation by Akt/ERK signaling pathway / 中国药理学通报

Aim To investigate the effect of licochalcone A (LCA) on proliferation and apoptosis of osteosarcoma HOS and U2OS cells and to explore its possible molecular mechanism. Methods The HOS and U2OS cells were cultured in vitro. MTT assay was used to detect the proliferation of the cells after being treated with different concentrations of LCA at different intervention time. Then HOS and U2OS cells were treated with 0. 1% DMSO, or different concentrations of LCA (5, 10, 20 μmol/L), and flow cytometry was used to assess the cell apoptosis. The expression of apoptosis-related protein cleaved PARP1, Bcl-2, Bax, and Akt, ERK were detected by Western blot. The antitumor effect of LCA was detected on U2OS xenograft mice in vivo. Results LCA could inhibit the proliferation of HOS and U2OS cells in a time-and dose-dependent manner. Flow cytometry showed that LCA treatment could induce cell apoptosis. Western blot results showed that LCA could inhibit the phosphorylation of Akt and ERK, increase the expression of cleaved PARP1 and Bax, and decrease the expression of Bcl-2. In the tumor-bearing mouse models, LCA significantly decreased the tumor volume (P < 0. 05) and weight (P < 0. 01). Conclusions LCA could inhibit the proliferation of HOS and U2OS and induce apoptosis possibly by inhibiting the Akt/ERK signaling pathway.