Research progress on clinical application and quality control of sprays / 药学实践杂志

Sprays have gained significant attention and widespread use due to their numerous advantages, including rapid action, safety, and convenience. They are widely used in various fields such as dermatology, respiratory disease treatment, wound repair, and central nervous system targeted drug delivery. With the in-depth research of new drugs and modern pharmaceutics, the development ideas of sprays are more diverse, and the application scenarios are increasingly extensive. In this review the clinical application status of sprays and the latest research progress were summarized. Then the quality control parameters were briefly introduced，which provided reference for the research and development of sprays.

Isolation of bone marrow mesenchymal stem cells in transgenic pigs and co-culture with porcine islets / 器官移植

Objective To investigate the isolation and culture of porcine bone marrow mesenchymal stem cell (BMSC) with α-1, 3-galactosyltransferase (GGTA1) gene knockout (GTKO), GTKO/ human CD46 (hCD46) insertion and cytidine monopho-N-acetylneuraminic acid hydroxylase (CMAH)/GGTA1 gene knockout (Neu5GC/Gal), and the protective effect of co-culture with porcine islets on islet cells. Methods Bone marrow was extracted from different transgenic pigs modified with GTKO, GTKO/hCD46 and Neu5GC/Gal. Porcine BMSC were isolated by the whole bone marrow adherent method and then cultured. The morphology of BMSC was observed and the surface markers of BMSC were identified by flow cytometry. Meantime, the multi-directional differentiation induced by BMSC was observed, and the labeling and tracing of BMSC were realized by green fluorescent protein (GFP) transfection. The porcine BMSC transfected with GFP were co-cultured with porcine islet cells. Morphological changes of porcine islet cells were observed, and compared with those in the porcine islet cell alone culture group. Results BMSC derived from pigs were spindle-shaped in vitro, expressing biomarkers of CD29, CD44, CD73, CD90, CD105 and CD166 rather than CD34 and CD45. These cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. Porcine BMSC with GFP transfection could be labeled and traced, which could be stably expressed in the daughter cells after cell division. Porcine BMSC exerted certain protective effect on islet cells. Conclusions GFP-labeled porcine BMSC modified with GTKO, GTKO/hCD46 and Neu5GC/Gal are successfully established, which exert certain protective effect upon islet cells.

Content measurement of doxorubicin hydrochloride and lonidamine by HPLC / 药学实践杂志

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 .

Preparation and pharmacokinetics of flumazenil sublingual tablet / 药学实践杂志

Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml−1, respectively; Cmax was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; tmax was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.

Impacts of aerobic exercise on cardiovascular health in college students / Impactos do exercício aeróbico na saúde cardiovascular dos estudantes universitários / Impacto del ejercicio aeróbico en la salud cardiovascular de los estudiantes universitarios

ABSTRACT Introduction Cardiovascular disease (CVD) is a major disease that seriously endangers human health. CVD in many adults begins in adolescence and even in childhood. The cardiovascular health of college students in China cannot be ignored. Objective Verify the impacts of aerobic exercise (APA) on the cardiovascular health of college students. Methods The paper uses the literature method to explore the health-promoting role of aerobic exercise in opposing and improving CVD. Also the APA exercise method of effectively improving cardiopulmonary fitness (CRF) to prevent and improve CVD. The results showed that APA can improve microcirculation by increasing microvascular reactivity. Results Coronary blood flow in healthy adults is only 8% to 9% of cardiac bleeding, while coronary blood flow increases by 40% and oxygen intake by 2-2.5 times. Aerobic exercise can improve insulin sensitivity and reduce the risk of CVD. Some risk factors related to vascular endothelial dysfunction, such as hypertension, atherosclerosis, and coronary artery disease, are often accompanied by the phenomenon of insulin resistance in the induction of CVD. At the same time, improving IR may play an effective role in preventing and treating CVD. Conclusion APA can reduce and suppress the occurrence and development of CVD risk factors such as atherosclerosis, hypertension, hyperlipidemia, hyperglycemia and obesity, intestinal microecological disorder, and reduce free radical oxidative damage and apoptosis by improving insulin sensitivity of vascular endothelial cells, inhibiting inflammatory reaction, improving mitochondrial function of cardiomyocytes, reducing body mass index and obesity, and maintaining gut micro-ecological balance, and improving vascular endothelial function and reducing CVD such as myocardial infarction. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

RESUMO Introdução A doença cardiovascular (DCV) é uma das principais doenças que colocam seriamente em risco a saúde humana. A DCV em muitos adultos começa na adolescência e até mesmo na infância. A saúde cardiovascular dos estudantes universitários na China não pode ser ignorada. Objetivo Verificar os impactos do exercício aeróbico (APA) sobre a saúde cardiovascular dos estudantes universitários. Métodos O artigo usa o método bibliográfico para explorar o papel de promoção da saúde do exercício aeróbico em oposição e melhoria da DCV. Também o método de exercício APA de melhorar efetivamente a aptidão cardiopulmonar (CRF) para prevenir e melhorar a DCV. Os resultados mostraram que a APA pode melhorar a microcirculação ao aumentar a reatividade microvascular. Resultados O fluxo de sangue coronariano em adultos saudáveis é apenas 8% a 9% do sangramento cardíaco, enquanto o fluxo de sangue coronariano aumenta em 40% e a ingestão de oxigênio em 2-2,5 vezes. O exercício aeróbico pode melhorar a sensibilidade insulínica e reduzir o risco de DCV. Alguns fatores de risco relacionados à disfunção endotelial vascular, tais como hipertensão, aterosclerose e doença arterial coronária, são frequentemente acompanhados pelo fenômeno de resistência à insulina na indução da DCV, enquanto a melhora da IR pode desempenhar um papel eficaz na prevenção e tratamento da DCV. Conclusão A APA pode reduzir e suprimir a ocorrência e o desenvolvimento de fatores de risco de DCV, tais como aterosclerose, hipertensão, hiperlipidemia, hiperglicemia e obesidade, distúrbio microecológico intestinal, além de reduzir os danos oxidativos radicais livres e a apoptose, melhorando a sensibilidade insulínica das células endoteliais vasculares, inibindo a reação inflamatória, melhorando a função mitocondrial dos cardiomiócitos, reduzindo o índice de massa corporal e a obesidade e mantendo o equilíbrio microecológico intestinal e melhorando a função endotelial vascular e reduzindo a DCV, como o infarto do miocárdio. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Las enfermedades cardiovasculares (ECV) son una de las principales enfermedades que ponen en grave peligro la salud humana. En muchos adultos, la ECV comienza en la adolescencia e incluso en la infancia. No se puede ignorar la salud cardiovascular de los estudiantes universitarios en China. Objetivo Verificar los impactos del ejercicio aeróbico (EAA) en la salud cardiovascular de los estudiantes universitarios. Métodos El artículo utiliza el método de la literatura para explorar el papel promotor de la salud del ejercicio aeróbico en la oposición y la mejora de la ECV. También el método de ejercicio APA para mejorar eficazmente la aptitud cardiopulmonar (CRF) para prevenir y mejorar la ECV. Los resultados mostraron que el APA puede mejorar la microcirculación al aumentar la reactividad microvascular. Resultados El flujo sanguíneo coronario en adultos sanos es sólo del 8% al 9% de la hemorragia cardiaca, mientras que el flujo sanguíneo coronario aumenta un 40% y el aporte de oxígeno entre 2 y 2,5 veces. El ejercicio aeróbico puede mejorar la sensibilidad a la insulina y reducir el riesgo de ECV. Algunos factores de riesgo relacionados con la disfunción endotelial vascular, como la hipertensión, la aterosclerosis y la enfermedad coronaria, suelen ir acompañados del fenómeno de la resistencia a la insulina en la inducción de la ECV, mientras que la mejora de la RI puede desempeñar un papel eficaz en la prevención y el tratamiento de la ECV. Conclusión El APA puede reducir y suprimir la aparición y el desarrollo de factores de riesgo de ECV como la aterosclerosis, la hipertensión, la hiperlipidemia, la hiperglucemia y la obesidad, el trastorno microecológico intestinal, y reducir el daño oxidativo de los radicales libres y la apoptosis mejorando la sensibilidad a la insulina de las células endoteliales vasculares, inhibir la reacción inflamatoria, mejorar la función mitocondrial de los cardiomiocitos, reducir el índice de masa corporal y la obesidad y mantener el equilibrio microecológico intestinal, así como mejorar la función endotelial vascular y reducir las ECV, como el infarto de miocardio. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Caffeic acid phenethyl ester improves peritoneal dialysis-associated peritoneal fibrosis by alleviating oxidative stress injury through activating nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway / 中华肾脏病杂志

Objective:To investigate whether caffeic acid phenethyl ester (CAPE) would improve peritoneal dialysis (PD)-associated peritoneal fibrosis by alleviating oxidative stress through activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into four groups by the random number table: control (CON) group (0.9% normal saline 20 ml/d intraperitoneal injection), CAPE group (0.9% normal saline 20 ml/d+CAPE 10 mg·kg -1·d -1 intraperitoneal injection), PD group [4.25% glucose peritoneal dialysis fluid (PDF) 20 ml/d intraperitoneal injection with lipopolysaccharide 0.6 mg/kg intraperitoneal injection at day 1, 3, 5 and 7], and PD+CAPE group (CAPE 10 mg·kg -1·d -1 intraperitoneal injection in addition to PD group), with 8 rats per group. On day 28, rats were euthanized after peritoneal equilibration test, and then the parietal peritoneum and omentum were collected for follow-up tests. To further investigate the mechanism, primary peritoneal mesothelial cells (PMCs) of rats were isolated and cultured. The PMCs were stimulated with 2.5% glucose PDF and added with 5 μmol/L CAPE intervention. The Nrf2 inhibitor (ML385) was used to identify whether CAPE protected PMCs from PDF by activating the Nrf2/HO-1 pathway. Histopathological staining was used to detect structural changes of the peritoneum, and immunohistochemical analysis was performed on cleaved caspase-3, Bax, α-smooth muscle actin (α-SMA), fibronectin (FN), and typeⅠ collagen (Col-Ⅰ) protein. Western blotting was used to detect the protein expression of α-SMA, FN, transforming growth factor-β1 (TGF-β1), HO-1 and nuclear Nrf2 (N-Nrf2). The apoptosis detection kit was used to detect apoptosis and flow cytometry was used to detect reactive oxygen species (ROS) in PMCs. The malondialdehyde (MDA) and superoxide dismutase (SOD) activity detection kit were used to detect MDA content and SOD activity. Cell immunofluorescence was used to analyze the protein expression of Nrf2 in PMCs. Results:Compared with the CON group, the PD group had thicker peritoneum, and the expression levels of cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰand MDA in peritoneum were significantly higher, while HO-1, N-Nrf2 protein expression and SOD activity were lower (all P<0.05). Compared with the PD group, the parietal peritoneum morphology of CAPE+PD group was improved, accompanied by reduced cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰ protein expression, and MDA content, while N-Nrf2, HO-1 protein expression, and SOD activity were higher (all P<0.05). Compared with the CON group, the PD group had significantly lower ultrafiltration volume and higher peritoneal permeability (both P<0.05). After CAPE intervention, the peritoneal transport function of the rats was significantly improved ( P<0.05). In cultured PMCs, PDF inhibited nuclear translocation of Nrf2 and protein expression of HO-1, and upregulated intracellular ROS level. In addition, PDF increased cell apoptosis and the protein expression levels of α-SMA, TGF-β1 and FN (all P<0.05). CAPE activated nuclear translocation of Nrf2, increased HO-1 protein expression, downregulated intracellular ROS level, and partially reversed PDF-induced cell apoptosis and epithelial- mesenchymal transition (all P<0.05). The protective effects of CAPE on PMCs were partially abolished by ML385 (all P<0.05). Conclusions:CAPE can reduce PD-induced PMCs apoptosis and epithelial-mesenchymal transition by attenuating oxidative stress, and significantly improve peritoneal fibrosis and ultrafiltration function. The beneficial effects of CAPE on peritoneum are related to activation of Nrf2/HO-1 pathway.

The effect and safety of first-line autologous hematopoietic stem cell transplantation in elderly patients with moderate/high-risk diffuse large B-cell lymphoma / 中华老年医学杂志

Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.

Research progress on effects of radiation exposure during pregnancy on offspring health / 中国辐射卫生

With social development and technology progress, there is an increasing use of daily electronic products and radioactive medical devices, which increases the risk of exposure to radiation in medical practices, daily life activities, and work. Notably, the effects of radiation exposure on pregnant women and their offspring have attracted increasing attention. Comprehensive and accurate assessment and intervention of the effects of radiation exposure on pregnant women and their offspring are of great significance to reduce birth defects and achieve eugenics. This article reviews the effects of radiation exposure during pregnancy on offspring health based on animal experiments and clinical studies, and describes the possible mechanisms, so as to provide the basis for further studies.

Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).@*METHODS@#Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).@*RESULTS@#The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).@*CONCLUSION@#TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

Application progress of ROS-responsive liposomes in anti-tumor research / 药学实践杂志

Reactive oxygen species（ROS） responsive liposomes are prepared based on the high level of ROS expression in the tumor microenvironment, enabling precise drug delivery to the tumor site. With the addition of photosensitizer, the controllability of drugs in liposomes can be further enhanced.

Establishment of determination of tetrodotoxin sustained-release microspheres / 药学实践杂志

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.

Screening of housekeeping genes in Gelsemium elegans and expression patterns of genes involved in its alkaloid biosynthesis / 生物工程学报

Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.

Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method / 中国中药杂志

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

Research progress on Huangqi Guizhi Wuwu Decoction and predictive analysis of quality markers / 中国中药杂志

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.

Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache / 中国中药杂志

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease / 中国中药杂志

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

Characterization of potential bitterness critical quality attributes in Xiaoer Ganmao Oral Liquid based on UHPLC-LTQ-Orbitrap MSn / 药学学报

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

Identification of taste critical quality attribute and formulation optimization of Xiaoer Qingrening Granules based on electronic tongue and human senses / 药学学报

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

Relationship between eating out and overweight， obesity， and fatty liver disease in adult residents in a suburban area of Shanghai / 上海预防医学

ObjectiveTo investigate the prevalence of overweight， obesity and fatty liver disease （FLD） in adult residents in a suburban area of Shanghai， and to explore the relationship between these conditions and eating out of home （EOH）. MethodsAdult residents from Zhongshan Street， Songjiang， Shanghai， were invited to report their frequency of EOH and undergo a physical examination using B-ultrasonography from May to September 2017. Binary logistic regression analyses were conducted to examine the relationship between EOH and conditions of overweight， obesity， and FLD. ResultsAmong the final sample size of 6 608 participants， the prevalence rates of overweight， obesity， and FLD were 41.65%， 14.71% and 38.29%， respectively. After adjusting for potential confounders， logistic analyses revealed that participants with an EOH frequency > once/week had a 1.44-fold higher prevalence of obesity （P=0.006）， a 1.35-fold higher prevalence of overweight/obesity （P=0.005）， and a 1.36-fold higher prevalence of FLD （P=0.008）. ConclusionThe prevalence of overweight， obesity， and FLD is relatively high in Songjiang， Shanghai. EOH may be a risk factor for these diseases， and residents are recommended to reduce the frequency of EOH.

Application of 3D ResSE-Unet-based intelligent delineation of clinical target volume in postoperative radiotherapy for breast cancer / 中华放射医学与防护杂志

Objective:To evaluate the effectiveness and feasibility of 3D ResSE-Unet-based intelligent delineation of clinical target volume (CTV) in postoperative adjuvant radiotherapy for breast cancer.Methods:A total of 974 cases of breast cancer treated in the Cancer Diagnosis and Treatment Center of the Fourth Affiliated Hospital of Guangxi Medical University from September 2018 to June 2022 were enrolled in this study, including 614 cases receiving total mastectomy and 360 cases treated with breast-conserving surgery. They were divided into a training set, a validation set, and a testing set. The training set consisted of 874 cases and was used to build a model of 3D ResSE-Unet-based intelligent CTV delineation. The validation set comprised 40 cases and was used to evaluate the feasibility and effectiveness of the clinical application of AI-based CTV design in the radiotherapy for breast cancer. The testing set was composed of 60 cases and was used to test the accuracy of intelligent CTV. The Wilcoxon rank test was used to compare the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and average surface distance (ASD) obtained using the intelligent delineation model.Results:The intelligent delineation model showed high precision. The CTV of cases treated with total mastectomy (CTV cw) and the CTV of cases treated with breast-conserving surgery (CTV b) had DSCs greater than 0.80 and greater than 0.88, respectively. Therefore, compared with CTV cw, CTV b had a higher DSC (0.91 ± 0.03 vs.0.83 ± 0.05, t = 7.11, P < 0.05). Both CTV cw and CTV b had lower HD 95 [(7.56 ± 3.42) mm vs.(8.77 ± 5.89) mm] and ASD [(1.85 ± 0.71) mm vs.(1.86 ± 0.83)mm], without statistically significant difference ( P > 0.05). The left/right supraclavicular and infraclavicular CTV (CTV2) had DSCs greater than 0.8. CTV2 also had low average HD95 and ASD, without statistically significant difference ( P > 0.05). Conclusions:The 3D ResSE-Unet-based intelligent CTV delineation has better consistency and feasibility in postoperative adjuvant radiotherapy for breast cancer, especially the CTVs after breast-conserving surgery.