The complete chloroplast genome of Aristolochia fangchi provided insights into the phylogeny and species identification of Aristolochia.

Aristolochia fangchi is an important species within the family Aristolochiaceae, most of which contain nephrotoxic aristolochic acid. The inadvertent use of Aristolochiaceae plants as raw ingredients in the manufacturing of patent medicine poses a significant risk warranting considerable attention. In this study, we assembled and analyzed the complete chloroplast genome of Aristolochia fangchi, which is a 159 867 bp long circular molecule. Functional annotation of the A. fangchi plastome unveiled a total of 113 genes, including 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Subsequently, a series of genome structure and characteristic evaluations were conducted against the A. fangchi plastome. Further phylogenetic analysis suggested that a plausible phylogenetic relationship among Aristolochiaceae derived from the concatenated sequences of shared conserved genes rather than from the entire chloroplast genome with one IR copy. Finally, a DNA polymorphism assessment against a dozen Aristolochia plastomes yielded multiple potential regions for biomarker designation. Six pairs of primers were generated and underwent both in silico and actual PCR validations. In conclusion, this study identified the unique characteristics of the A. fangchi plastome, providing invaluable insights for further investigations on species identification and the phylogeny evolution between A. fangchi and its related species.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

A phase I, single-sequence, open-label study to evaluate the drug-drug interaction between hetrombopag and cyclosporine in healthy Chinese subjects.

AIMS: This study aims to evaluate the drug-drug interaction (DDI) between hetrombopag and cyclosporine in healthy Chinese subjects. METHODS: Twenty-six eligible subjects enrolled in this single-centre, single-sequence, open-label, DDI study with 3 treatment periods, receiving 5 mg hetrombopag once on Day 1, 100 mg cyclosporine twice daily from Day 11 to Day 15 and 5 mg hetrombopag + 100 mg cyclosporine on Day 16. Serial blood samples were collected for pharmacokinetic evaluation. Adverse events were monitored throughout the study. RESULTS: The plasma hetrombopag geometric mean ratios (90% confidence interval) of maximum plasma concentration, area under the plasma concentration-time curve (AUC) from predose to time of last quantifiable sample and AUC to infinity of coadministration of hetrombopag with cyclosporine vs. hetrombopag alone were 95.97% (70.08-131.43%), 105.75% (75.04-149.04%) and 104.19% (74.71-145.32%), respectively, indicating multiple doses of cyclosporine had minimal effects on hetrombopag exposure. The geometric mean ratios (90% confidence interval) of maximum blood concentration and AUC at steady state during a dosing interval for blood cyclosporine of coadministration vs. cyclosporine alone were 100.49% (91.89-109.89%) and 100.81% (107.88-103.82%), respectively, suggesting a single dose of hetrombopag had no impact on the exposure of cyclosporine. Coadministration of hetrombopag with cyclosporine was generally well tolerated. CONCLUSION: No clinically significant DDI was observed when coadministration of hetrombopag with cyclosporine. The results of this study will inform the appropriate use of this combination therapy both in clinical trials and clinical settings.

A Single-dose, Two-Period Crossover Bioequivalence Study Comparing Two Liraglutide Formulations in Healthy Chinese Subjects.

Liraglutide, a glucagon-like peptide 1 receptor agonist, is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. The original liraglutide products are costly, which limits patient access to this therapeutic treatment. Herein, a biosimilar was developed that is highly similar to the reference drug in molecular structure and bioactivity, and is expected to have similar pharmacokinetic (PK) and safety profiles in clinical studies. This study aimed to primarily evaluate the bioequivalence of 2 liraglutide formulations and secondarily assess their safety in healthy Chinese subjects following a single-dose subcutaneous injection. Thirty-two healthy volunteers were recruited in this randomized, open-label, single-dose, 2-period crossover bioequivalence study (ChiCTR2100043348). The geometric mean ratios (GMRs) of the test drug to the reference drug (T/R) and corresponding 90% confidence intervals (CIs) for maximum concentration (Cmax ) and the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t ) were estimated using a mixed-effects model, and bioequivalence was determined to have been achieved if the 2-sided 90%CI fell within the predefined range of 80%-125%. PK parameters were comparable between T and R, with GMRs of T/R for Cmax and AUC0-t being 105.7% and 107.7%, respectively, the 90%CI of which met the acceptance criteria for bioequivalence. We also observed a similar and favorable safety profile in the T and R arms, with adverse events being predominantly mild in severity and of gastrointestinal origin. Our findings indicate that the test drug is safe and well tolerated, bioequivalent to the reference drug, and warrants further testing in a phase III clinical trial.

Effectiveness and safety of Danmu extract syrup for acute upper respiratory tract infection in children: A real-world, prospective cohort study.

AIM: To evaluate the effectiveness and safety of Danmu Extract Syrup for the treatment of acute upper respiratory tract infection (AURI) in children. METHODS: In this prospective cohort study, we enrolled children with AURI in the pediatric outpatient department and emergency department of West China Second Hospital. According to the treatment, they were divided into two groups: Danmu Extract Syrup Group (Danmu Group) and Xiaoer Chiqiao Granule Group (Chiqiao Group). The primary outcome was time to symptom remission, and the secondary outcomes were defervescence time, relief time, admission rate, and adherence. We used restricted mean survival time (RMST) to quantify the treatment effects and test noninferiority for primary outcome. Propensity score matching (PSM) was used to adjust confounding. Subgroup analysis and sensitivity analysis were used to verify the robustness of results. RESULTS: We enrolled 1036 children with AURI, including 516 in Danmu Group and 520 in Chiqiao Group. After PSM, no significant difference was observed in the baseline characteristics of the two groups. The primary results showed that the RMST difference was -3 h (95% CI: -15.1 to 9.1) and the upper limit of the 95% CI was less than the noninferiority margin of 11 h. There was no statistical difference in the secondary outcomes except for defervescence between the two groups. The results of safety analysis showed that the incidence of adverse events occurred is 4.1% in Danmu Group, which was lower than the incidence of Chiqiao Group (6.9%). CONCLUSION: This study indicated that Danmu extract syrup is noninferiority to Chiqiao Granule for AURI in children.

Characterization of the Complete Chloroplast Genome of Buddleja lindleyana.

BACKGROUND: Buddleja lindleyana Fort., which belongs to the Loganiaceae with a distribution throughout the tropics, is widely used as an ornamental plant in China. There are several morphologically similar species in the genus Buddleja, but the lack of comprehensive molecular and phylogenetic studies makes it difficult to distinguish related species, which hinders further studies of this genus. OBJECTIVE: Using molecular biology techniques to sequence and analyze the complete chloroplast (cp) genome of B. lindleyana. METHODS: After sequencing of the genomic DNA using next-generation sequencing, a series of bioinformatics software were used to assemble and analyze the molecular structure of the cp genome of B. lindleyana. RESULTS: The complete cp genome of B. lindleyana is a circular 154 487-bp-long molecule with a GC (Guanine and Cytosine) content of 38.1%. It has a quadripartite structure, including a LSC region (85 489 base pair (bp)), a small single-copy region (17 898 bp), and a pair of inverted repeat regions (25 550 bp). A total of 133 genes were identified in this genome, including 86 protein-coding genes, 37 tRNA (transfer Ribonucleic Acid) genes, eight rRNA (ribosomal Ribonucleic Acid) genes, and two pseudogenes. CONCLUSION: These results suggest that the B. lindelyana cp genome could be used as a potential genomic resource to resolve the phylogenetic positions and relationships of Loganiaceae, and will offer valuable information for future research in the identification of Buddleja species and will conduce to genomic investigations into these species. HIGHLIGHTS: This paper study the B. lindelyana cp genome and it's structural characteristics, and analyze the phylogeny of Loganiaceae.

Clinical pharmacist participation in selecting and dosing targeted drugs for a patient with ALK-positive non-small cell lung cancer: a case report.

Ceritinib and alectinib are recommended as the second-line therapies in the 2019 Chinese Society of Clinical Oncology (CSCO) guidelines for patients with anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) in whom the first-line therapy has failed, but no optimal second-line treatment has been identified. Before 2018, the approved dose of ceritinib in the United States and many other countries was 750 mg/d fasted. In China, the approved dose was 450 mg/d fed although the dose of 750 mg/d fasted is still used in clinical practices. In our current case, a clinical pharmacist was involved in the selection and dose adjustment of a targeted drug for an ALK-positive NSCLC patient. The selection of second-line targeted drugs is based mainly on the results of clinical trials and real-world data of ceritinib and aletinib, along with the comprehensive analysis of health insurance policy, pharmacoeconomics, and drug accessibility. Alectinib may be more efficacious than ceritinib is in second-line settings. However, in our current case, the patient finally chose ceritinib after considering the drug prices and the health insurance policy. The clinical pharmacist optimized the dosage of ceritinib from 750 mg/d fasted to 450 mg/d fed, which not only improved the patient's medication compliance but also ensured the safety and efficacy of the drug; in addition, it lowered the financial burden of both the health insurance system and the patient, offering a good example for rational drug use and health insurance cost reduction. In conclusion, in choosing second-line targeted therapy for ALK-rearranged NSCLC, a variety of factors should be considered, including clinical efficacy, adverse effects, health insurance policy, drug price, and drug accessibility, and the dosage of ceritinib should be optimized to 450 mg/d fed in real-world settings.

The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18-59 years: A phase I randomized, double-blinded, controlled trial.

BACKGROUND: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. METHOD: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated. RESULTS: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine. INTERPRETATION: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. TRIAL REGISTRATION: CTR20200943 and NCT04412538.

Fear and anxiety about COVID-19 among local and overseas Chinese university students.

This study aimed to establish a new COVID-19 Fear (Higher Education) scale to investigate the relationship between fear and generalised anxiety symptoms among Chinese students in mainland China, Hong Kong, and other countries. 219 Chinese university students studying in universities in mainland China (n = 76, 34.7%), Hong Kong (n = 66, 30.1%), and overseas (i.e., outside of China as international students, n = 77, 35.2%) participated in an online study from March 31, 2020 to April 4. Participants completed a newly developed COVID-19 Fear (Higher Education) scale to measure three domains of fear including fear of infection, fear of instability and fear of insecurity related to the COVID-19 pandemic. They also completed the Generalized Anxiety Disorder 7-item scale (GAD-7) on the severity of anxiety symptoms. About 9.6% of the participants could be classified as exhibiting high anxiety level according to the GAD-7. More students studying overseas (about 15%) were classified into the high GAD group when compared to students studying in both mainland China (6.6%) and Hong Kong (6.1%). MANOVA results showed that students studying in Hong Kong and overseas had more concerns related to preventive measures related to COVID-19 than their mainland counterparts did. We concluded that international students studying away from their home country would have higher risk to develop anxiety problems during a collective trauma such as the COVID-19 pandemic. Education institutions should provide support services including online support groups, social media groups for mutual support to alleviate the fear and anxiety of international students.

[LC-MS/MS Determination of Tenofovir in Human Plasma and Its Bioequivalence].

OBJECTIVE: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting tenofovir in human plasma. METHODS: Twenty four healthy male volunteers received a single oral dose of 300 mg tenofovir disoproxil fumarate tablets under fasting and high-fat diet conditions in a randomized four-way crossover bioequivalence study with two preparations of tablets. Plasma samples were taken and analyzed using the LC-MS/MS method. The pharmacokinetic parameters of the two preparations were calculated and compared statistically to evaluate their bioequivalence using Phoenix Winnonlin6.3. RESULTS: Linear detection responses were obtained for tenofovir at the range from 3.13 to 500 ng/mL. The intra- and inter-day precisions were high,with lower than 5.43% [relative standard deviation (RSD)%],high recovery and good stability. The 90% confidence intervals of peak concentration (Cmax) of tenofovir and its area under the curve (AUC0-t and AUC0-∞ ) all fell within the bioequivalence limit 80.00%-125.00% under both fasting and high-fat diet conditions. No significant difference in peak time (Tmax) was demonstrated between the two preparations (P>0.05) . CONCLUSION: The LC-MS/MS method can be used for simultaneous determination of tenofovir in human plasma. The two preparations of tablets are bioequivalent.

[Pharmacokinetics Study of Phentolamine Mesylate Injection in Healthy Volunteers].

OBJECTIVE: To study the pharmacokinetic profile of phentolamine mesylate injection in healthy Chinese volunteers. METHODS: A total of 16 healthy volunteers were randomly divided into two groups, each receiving anterior teeth submucosal infiltration anesthesia and inferior alveolar nerve block anesthesia, respectively. The participants were injected with 0.9 mL, 1.8 mL, and 3.6 mL of 2% lidocaine HCl with 1∶100 000 epinephrine over three periods sequentially, followed by corresponding sequential injection of 0.2 mg, 0.4 mg, 0.8 mg of phentolamine mesylate at the same sites 30 min later.Blood samples were drawn from 5 min before injection to 15 h post the injection of phentolamine mesylate (16 time points). Adverse events were closely observed all the time. Plasma phentolamine mesylate was detected using UPLC-MS/MS with isotope as internal standard. WinNolin 6.1 software was used to calculate the pharmacokinetic parameters. RESULTS: Time to peak concerntration (Tmax) ranged from 12 to 13 min. Half-time of elimination (t1/2) ranged from 3.84 to 4.07 h, with a clearance (CL) of 190 L/h. Peak concentration (Cmax), area under concentration-time curves from 0 to t hour and from 0 to infinite time (AUC0-t and AUC0-∞) increased proportionally in the dose range of 0.2 mg to 0.8 mg. The results of confidence interval analysis showed nearly linear dynamic characteristics for the injection of phentolamine mesylate. All participants experienced mild adverse events, including pain at the injection point, dizziness, and palpitations. These adverse events disappeared without treatments. CONCLUSIONS: Phentolamine mesylate injection is effective for reversing oral local anesthetic effects.