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 .

Single-bolus dexmedetomidine in prevention of emergence delirium in pediatric ophthalmic surgeries: A randomized controlled trial

Purpose: Emergency delirium (ED), a common postoperative neurologic complication, causes behavioral disturbances leading to self?traumas and also has long?term adverse effects in children. Our aim was to investigate the efficacy of a single?bolus dose of dexmedetomidine in reducing the incidence of ED. Additionally, pain relief, number of patients who needed rescue analgesia, hemodynamic parameters, and adverse events were assessed. Methods: One hundred and one patients were randomly allocated into two groups: 50 patients received 15 mL of dexmedetomidine 0.4 ?g/kg (group D) and 51 patients received volume?matched normal saline (group C). Hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were monitored regularly throughout the procedure. ED was assessed with Pediatric Anesthesia Emergence Delirium Scale (PAEDS), and pain was measured using the modified Objective Pain Score (MOPS). Results: The incidences of ED and pain were higher in group C than group D (P < 0.0001 and P < 0.0001, respectively). Group D showed significant decrease in MOPS and PAEDS values at 5, 10, 15, and 20 min (P < 0.05), HR at 5 min (P < 0.0243), and SBP at 15 min (P < 0.0127). There was no significant difference in DBP between the two groups at any time point. The mean blood pressure (MBP) at 10 min was significantly less in group D than group C (P < 0.001). Conclusion: Dexmedetomidine 0.4 ?g/kg as a single bolus over 10 min immediately after intubation is effective for the prevention of ED and significantly reduces the need of rescue analgesia without compromising the hemodynamic parameters in children undergoing ophthalmic surgery.

De-escalação de inibidores dos receptores P2Y12 após intervenção coronária percutânea / P2Y12 inhibitor de-escalation after percutaneous coronary interventions

Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.

In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.

Osimertinibe comparado a Erlotinibe Gefitinibe ou quimioterapia para tratamento de carcinoma pulmonar de células não pequenas com mutação do gene do receptor do fator de crescimento epidérmico (EFGR): revisão rápida / Osimertinib compared to erlotinib, gefitinib or chemotherapy for the treatment of non-small cell pumonary carcinoma with epidermal growth factor receptor (EFGR) gene mutation: rapid review

Mesilato de osimertinibe, gefitinibe, erlotinibe, quimioterapia padrão. Indicação: Câncer de pulmão de células não pequenas com mutação do receptor do fator de crescimento epidérmico (EGFR). Pergunta: Mesilato de osimertinibe é mais eficaz e seguro que gefitinibe, erlotinibe ou quimioterapia para os desfechos de sobrevida global, sobrevida livre de progressão e de segurança no tratamento de carcinoma pulmonar de células não pequenas com mutação do EGFR? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED e EPISTEMONIKOS, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atenderam aos critérios de elegibilidade. Conclusão: Mesilato de osimertinibe é mais eficaz do que gefitinibe ou erlotinibe na melhora da sobrevida global e da sobrevida livre de progressão em pacientes virgens de tratamento. Em pacientes previamente tratados, o mesilato de osimertinibe não é superior à quimioterapia padrão à base de platina no prolongamento da sobrevida global, mas é mais eficaz no aumento da sobrevida livre de progressão. Para câncer avançado, mesilato de osimertinibe não é mais eficaz do que a quimioterapia com ou sem pemetrexede para prolongar a sobrevida global, mas é mais eficaz em melhorar a sobrevida livre de progressão. Gefitinibe combinado com quimioterapia à base de pemetrexede foi superior à quimioterapia com ou sem pemetrexede na melhora da sobrevida global e da sobrevida livre de progressão

Osimertinib mesylate, gefitinib, erlotinib, standard chemotherapy. Indication: Non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutation. Question: Is osimertinib mesylate more effective and safer than gefitinib, erlotinib or chemotherapy for overall survival, progression-free survival and safety outcomes in the treatment of non-small cell lung cancer with EGFR mutation? Methods: A bibliographic search was done in the PUBMED and EPISTEMONIKOS database, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the Assessing the Methodological Quality of Systematic Reviews Version 2 tool. Results: Two systematic reviews were selected because they met the eligibility criteria. Conclusion: Osimertinib mesylate is more effective than gefitinib or erlotinib in improving overall survival and progression-free survival in treatment-naive patients. In previously treated patients, osimertinib mesylate is not superior to standard platinum-based chemotherapy in prolonging overall survival, but it is more effective in increasing progression-free survival. For advanced cancer, osimertinib mesylate is not more effective than chemotherapy with or without pemetrexed in prolonging overall survival, but it is more effective in improving progression-free survival. Gefitinib combined with pemetrexed-based chemotherapy was superior to chemotherapy with or without pemetrexed in improving overall survival and progression-free survival

Comparison of efficacy，safety and economics of bid-winning and original Moxifloxacin hydrochloride tablets in the treatment of outpatient community-acquired pneumonia / 中国药房

OBJECTIVE To compare the efficacy， safety and economics of bid-winning and original Moxifloxacin hydrochloride tablets in the treatment of outpatient community-acquired pneumonia （CAP）. METHODS A retrospective cohort study was conducted to screen and include CAP outpatients during the period of January to December 2021 in Lianyungang First People’s Hospital. They were divided into generic drug group （1 058 cases） and bid-winning drug group （1 121 cases） according to the drug source. Two groups were respectively given original and bid-winning Moxifloxacin hydrochloride tablets， 0.4 g each time， once a day. The efficacy indexes （clinical effective rate， remission time， treatment course， revisiting rate） and safety indexes （allergy， nervous system symptoms， etc.） were compared between the two groups； and the influence factors of clinical treatment failure were analyzed with multi-factor modified Poisson regression model. The economic indicators of the two drugs [quantity， consumption sum， defined daily doses （DDDs）， defined daily dose cost （DDDc）， price ratio， replacement rate] were compared. RESULTS There were no significant differences in the clinical effective rate， treatment course， revisiting rate， the incidence of nervous system symptoms and Q-T interval prolongation between the two groups （P＞0.05）. The remission time of original drug group was significantly shorter than that of bid-winning drug group， and the incidence of total adverse drug reaction， allergy reaction， gastrointestinal symptom reaction and hyperglycemia were significantly lower than those in bid-winning drug group（P＜0.05）. Multivariate Poisson regression analysis showed that bid-winning drug did not increase the risk of clinical treatment failure in CAP outpatients [RR＝1.132， 95%CI （0.883， 1.542）， P＝0.327]. However， antibiotic exposure history， more than 2 items of abnormal clinical manifestations and auxiliary examination all increased the risk of clinical treatment failure （P＜0.05）. Compared with before the implementation of centralized volume-based procurement policy， the quantity and DDDs of Moxifloxacin hydrochloride tablets increased significantly， while the consumption sum decreased significantly， DDDc of bid-winning drug decreased significantly， the price ratio of it to original drug decreased to 0.117， and the replacement rate increased to 69.44% after the implementation of centralized volume- based procurement policy. CONCLUSIONS Compared with original drug， bid-winning Moxifloxacin hydrochloride tablet shows reliable efficacy and obvious price advantage in the treatment of outpatient CAP， but the incidence of adverse drug reactions is higher.

Evaluation on genotoxicities of raceanisodamine hydrochloride injection / 药学实践杂志

Objective To study the genotoxicities of raceanisodamine hydrochloride injection. Methods Bacterial reverse mutation test, in vitro Chromosomal aberration test and in vivo Micronucleus test were performed to investigate the genotoxicities of raceanisodamine hydrochloride injection. Results The Ames test showed that raceanisodamine hydrochloride injection did not increase mutagenicity for TA1535, TA102, TA100, TA98 and TA97 strains at the dosage of 0.5, 5, 50, 500, 5000 μg per plate under two parallel system conditions (±S9). Results of CA test indicated that there was no statistical difference between raceanisodamine hydrochloride injection groups (doses of 58.75,117.5 and 235.0 μg/ml) and the solvent control group under two parallel system conditions (±S9). In MNT test, with doses of 7.5, 15.0 and 30.0 mg/kg respectively, the micronucleus induction rate of bone marrow of ICR mice was not statistically significant (P>0.05) when compared with that of vehicle control group in all dose groups. Conclusion Under the conditions of these study, the results indicated that raceanisodamine hydrochloride injection had no mutagenicity to Salmonella typhimurium, had no aberration effect on the chromosome of mammalian cultured cells, and had no effect on inducing micronucleus of bone marrow polychromatic erythrocytes in ICR mouse. All test results showed that raceanisodamine hydrochloride injection had no potential carcinogenicities and genetic toxicities under the test conditions.

Studies on orally disintegrating tablet of diphenhydramine hydrochloride and caffeine / 药学实践杂志

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.

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Effects of metformin hydrochloride tablets on clinical efficacy and number of dominant follicles in polycystic ovary syndrome / 药学实践杂志

Objective To explore the effect of metformin hydrochloride tablets on the clinical efficacy, number of dominant follicles and ovarian volume of polycystic ovary syndrome. Methods 150 patients diagnosed with polycystic ovary syndrome who were diagnosed and treated in our hospital from January 2019 to March 2021 were selected .The patients were divided into observation group and control group by random number table. The control group was treated with letrozole + gonadotropin, and the observation group was treated with letrozole + gonadotropin + hydrochloric acid + Metformin tablets. The clinical efficacy, endometrial thickness, number of high-quality follicles, sex hormone levels, blood lipid levels, and adverse reactions were compared between the two groups. Results ① The effective rate of treatment in the observation group was 90.67%, which was significantly higher than that in the control group, 78.67% (P<0.05). ② After treatment, the endometrial thickness of the observation group was lower than that of the control group, and the number of high-quality follicles was more than that of the control group(P<0.05). ③ After treatment, the levels of Luteinizing Hormone-LH, Follicle Stimulating Hormone-FSH and Testosterone (T) in the observation group were lower than those in the control group (P<0.05). ④ After treatment, the total cholesterol (TC) and triglyceride (TG) in the observation group were lower than those in the control group (P<0.05). ⑤ The incidence of adverse reactions in the observation group was 8.00%, which was significantly lower than 20.00% in the control group (P<0.05). Conclusion Letrozole + gonadotropin + metformin hydrochloride tablets could significantly improve the sex hormone and blood lipid levels in patients with polycystic ovary syndrome, relieve the symptoms of the patients, and improve their uterine condition, which had a good clinical effect.

Memantine hydrochloride promotes the antibacterial effect of neutrophils against methicillin-resistant Staphylococcus aureus and the related mechanism / 中华微生物学和免疫学杂志

Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

Clinical observation of Mahuang Fuzi Xixin Decoction combined with balanced acupuncture in the treatment of Migraine with Yang deficiency and cold coagulation / 国际中医中药杂志

Objective:To observe the clinical efficacy of Mahuang Fuzi Xixin Decoction combined with balanced acupuncture in the treatment of migraine with yang deficiency and cold congealing syndrome.Methods:Randomized controlled trial. Totally 91 cases of migraine with yang deficiency and cold congealing syndrome in our hospital from March 2021 to May 2022 were selected and divided into 45 cases in the Western medicine group and 46 cases in the integrated Chinese and Western medicine group according to random number table method. The Western medicine group took flunarizine hydrochloride capsules orally, and the integrated Chinese and Western medicine group combined ephedrine and aconiti asarum decoction + balanced acupuncture treatment on the basis of the Western medicine group. Both groups were treated for 1 month. Traditional Chinese Medicine syndrome score was performed before and after treatment, the degree of headache was assessed by VAS scale, and the impact of headache on life was assessed by Headache Impact Test-6 (HIT-6); the levels of 5-hydroxytryptamine (5-HT) and calcitonin gene related peptide (CGRP) were determined by radioimmunoassay. The adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 82.22% (37/45) in the Western medicine group and 95.65% (44/46) in the integrated Chinese and Western medicine group, with statistical significance ( χ2=4.20, P=0.041). After treatment, the scores of headache, hair, urine and cold limbs in the integrated Chinese and Western medicine group were lower than those in the Western medicine group ( t values were 18.49, 22.29, 21.31, 27.49, P<0.01), and the scores of VAS and HIT-6 were lower than those in the Western medicine group ( t values were 23.20, 9.33, P<0.01). After treatment, the level of 5-HT in the integrated Chinese and Western medicine group [(98.34±6.23) μg/L vs. (85.23±4.21) μg/L, t=11.74] was higher than that of the Western medicine group ( P<0.01); CGRP [(11.24±1.99) ng/L vs. (15.22±2.52) ng/L, t=8.37] was lower than that of the Western medicine group ( P<0.01). During treatment, the incidence of adverse reactions was 2.22% (1/45) in the Western medicine group and 2.17% (1/46) in the integrated Chinese and Western medicine group, without statistical significance ( P>0.05). Conclusion:Mahuang Fuzi Xixin Decoction combined with balanced acupuncture can effectively improve the clinical symptoms and life quality of patients of migraine with yang deficiency and cold congealing, and the clinical efficacy can be promoted.

Clinical study on modified self-made Qingxin Buqi Pinggan Decoction combined with atomoxetine hydrochloride in the treatment of attention deficit hyperactivity disorder / 国际中医中药杂志

Objective:To evaluate the efficacy of modified self-made Qingxin Buqi Pinggan Decoction combined with atomoxetine hydrochloride in the treatment of attention deficit hyperactivity disorder (ADHD).Methods:Randomized controlled trial. A total of 200 children with ADHD admitted to our hospital from January 2020 to January 2022 were selected as observation subjects by prospective cohort study, and were divided into two groups according to the random number table method. The control group was given oral administration of atomoxetine hydrochloride capsules, and the observation group was given self-made Qingxin Buqi Pinggan Decoction on the basis of the control group. Both groups were treated continuously for 3 months. Before and after treatment, the Traditional Chinese Medicine symptoms were scored, and the core symptoms of the children were evaluated by Swanson Nolan and Pelham-versionⅣ (SNAP-Ⅳ), and the hyperactivity tendency was assessed by Parent Symptom Questionnaire (PSQ). The serum cortisol (COR) and adrenocorticotropic hormone (ACTH) levels were measured by chemiluminescence immunoassay. Adverse reactions during treatment were observed and clinical efficacy was evaluated.Results:The total effective rate was 97.0% (97/100) in observation group and 88.0% (88/100) in control group ( χ2=5.84, P=0.016). After treatment, the scores of restlessness, hyperactivity, unsteadiness, emaciation, lusterless complexion and restless sleep in the observation group were significantly lower than those in the control group ( t=17.90, 11.79, 10.01, 23.27, 11.79, 12.03, P<0.01). The scores of impulsivity factor, learning factor, hyperactivity factor, behavior factor, psychosomatic factor and anxiety factor were significantly lower than those in the control group ( t=4.65, 42.83, 10.01, 41.89, 39.42, 18.30, P<0.01). The scores of attention deficit, hyperactivity-impulsivity and behavior performance were significantly lower than those in the control group ( t=11.68, 9.69, 28.42, P<0.01). After treatment, the levels of serum COR [(337.26±17.22) nmol/L vs. (275.51±15.49) nmol/L, t=26.66] and ACTH [(24.47±1.12) ng/L vs. (19.23±1.43) ng/L, t=28.85] were significantly higher in observation group than those in the control group ( P<0.01). During treatment, the incidence rate of adverse reactions was 6.0% in observation group and 5.0% in control group ( χ2=0.10, P=0.756). Conclusion:Modified self-made Qingxin Buqi Pinggan Decoction combined with atomoxetine hydrochloride can improve the clinical symptoms of children with ADHD, reduce the degree of hyperactivity disorder, increase the levels of serum COR and ACTH, and enhance the clinical efficacy.

Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT) / 白血病·淋巴瘤

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Structural elucidation and mechanism study for Hofmann-Martius-like rearrangement products in duloxetine hydrochloride under the process condition / 中国药科大学学报

@#Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.

Retrospective Analysis of Death Cases of Oral Diphenidol Hydrochloride Poisoning / 法医学杂志

OBJECTIVES@#To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths.@*METHODS@#The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected.@*RESULTS@#In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied.@*CONCLUSIONS@#Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

A short-term efficacy evaluation of biological antibacterial peptides in the adjuvant therapy of stageⅢ periodontitis / 口腔医学

Objective@#To investigate the efficacy of antibacterial peptides in the adjuvant therapy of stage Ⅲ periodontitis.@*Methods@#Fifty-one patients were randomly divided into simple mechanical curettage group, minocycline hydrochloride group and antibacterial peptide group according to the treatment mode. Three groups received periodontal sequential treatment, and after the ultrasonic supragingival scaling, they were performed with curettage, root surface planing, polishing and flushing. After treatment in the minocycline hydrochloride group and the biological antibacterial peptide group, minocycline hydrochloride ointment and biological antibacterial peptide periodontal gel were injected into the periodontal pocket respectively. The mechanical curettage group did not take medicine. Periodontal checklists at baseline and 90 d after treatment were recorded to compare differences of the three groups in periodontal probing depth (PD), bleeding index (BI) and attachment level (AL). Enzyme-linked immunosorbent assay (ELSIA) was used to detect the change of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β by collecting the gingival crevicular fluid of the three sets at baseline, 7 d after treatment and 90 d after treatment. @*Results@#There was no statistically significant difference in periodontal clinical examination indexes(PD,BI,AL) and contents of TNF-α and IL-1β in the gingival crevicular fluid between the three groups at baseline (P>0.05). At 7 and 90 d after treatment, all indexes in the three groups were improved compared with those before treatment. The comparison between groups showed that in periodontal pockets with PD≤5 mm, there was no statistically significant difference in the indicators between the three groups. In periodontal pockets with PD≥6 mm, the minocycline hydrochloride group and the bio-antibacterial peptide group had no statistically significant difference in various indicators, but they were all better than the mechanical scaling group.@*Conclusion@#Basic periodontal therapy is an important treatment for stage Ⅲ periodontitis. Minocycline hydrochloride and biological antibacterial peptides are both effective adjuvant drugs for deep periodontal pockets with PD≥6 mm.

Inhibitory effects of gemcitabine hydrochloride combined with ferroptosis inducers on the proliferation of PANC-1 cells / 药学实践杂志

Objective To study the effects of three ferroptosis inducers Erastin (Era), sulfasalazine (SASP) and artesunate (Art) alone or combined with gemcitabine hydrochloride (hcGEM) on the proliferation inhibition of Human pancreatic cell line PANC -1. Methods The CCK-8 method was used to detect the inhibitory effects of different concentrations of Era, SASP and Art alone or combined with hcGEM on the proliferation of PANC-1, and the combination index (CI) was used to judge whether three ferroptosis inducers combined with hcGEM had synergistic inhibitory effect on PANC-1. Results The three ferroptosis inducers and hcGEM alone or in combination could significantly inhibit the activity of PANC-1. The inhibitory effects were enhanced with the concentration increasing. The CI values of hcGEM-Era 4∶1 or 1∶4 combination group and hcGEM-SASP 1∶400 combination group were less than 1.The CI values of hcGEM-Art 1∶4 or 1∶16 combination group were less than 1 only within a certain concentration range. Conclusion The inhibitory effects of the three ferroptosis inducers and hcGEM alone or in combination were dose-dependent. The combination of hcGEM and three ferroptosis inducers could synergistically inhibit the proliferation of PANC-1.

Content determination of 5-HMF in glucosamine hydrochloride tablets and formation kinetics study / 中国药房

OBJECTIVE To establish the method for the content determination of 5-hydroxymethylfurfural （5-HMF） in glucosamine hydrochloride tablets， and to analyze its regularity and influential factors. METHODS Quantitative analysis of 5-HMF was performed using high-performance liquid chromatography. The analysis was conducted on Shim-pack GIST C18-AQ column with mobile phase consisted of 0.1% phosphoric acid solution-methanol （90∶10， V/V） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， and detection wavelength was 284 nm. The injection volume was 20 μL. Reaction kinetics test of different temperatures was adopted to analyze the relationship of 5-HMF content with reaction temperature and reaction time， and utilized to build its formation kinetic model. RESULTS The linger range of 5-HMF was 0.057-5.698 μg/mL （r＝0.999 9）. The limits of detection and quantitation were 5.70 and 17.09 ng/mL； RSDs of precision， repeatability and stability （24 h） tests were all lower than 1.0% （n＝6）. The average recoveries ranged from 99.38% to 99.73%（RSD＝0.53%， n＝9）. The contents of the 5-HMF in 8 batches of samples ranged 4.10-35.13 μg/g. Results of data fitting in reaction kinetics test showed that the higher reaction temperature and the longer reaction time， the higher 5-HMF content in the sample. At 50， 60， 70 and 80 ℃ ， the relationship between the content of 5-HMF and the reaction time was linear， in accordance with a zero-order kinetic model. The reaction rate constants were 6.789， 7.715， 8.815 and 11.430， respectively. CONCLUSIONS The established method has strong specificity， high sensitivity， and good accuracy； the reaction temperature and reaction time are important influential factors for the formation of 5-HMF in glucosamine hydrochloride tables. The change rule of its content conforms to the zero-order kinetic model.