As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.
Rats ; Male ; Animals ; Rats, Wistar ; Altitude ; Semen/metabolism* ; Hypoxia/pathology* ; Genitalia, Male

ObjectiveTo explore the effect and mechanism of Lactobacillus paracasei （Lpa） on the prevention of atherosclerosis. MethodsEight-week-old male ApoE^-/- mice were used to establish the atherosclerotic model， and the mice were randomly divided into three groups： ① normal chow control group： ApoE^-/- + normal chow diet （n=10）； ② model group： ApoE^-/- + western diet + PBS （n=10）； ③ Lactobacillus paracasei intervention group： ApoE^-/- + western diet + Lactobacillus paracasei （n=10）. followed by histological evaluations of atherosclerotic lesion in aorta. Immunofluorescence analysis was used to measure the cholesterol accumulation and cholesterol uptake of peritoneal macrophages. Western blot was used to measure the protein expression level of class A scavenger receptor （SR-A） and class B scavenger receptor （CD36）. ResultIntervention of Lactobacillus paracasei can significantly suppress the formation of atherosclerotic plaque in ApoE^-/- mice， reduce the inflammatory reaction of arterial blood vessels， inhibit the lipid accumulation and cholesterol uptake of macrophages， and reduce the protein expression of SR-A. ConclusionsLactobacillus paracasei may protect against atherosclerosis by preventing the inflammation of arterial blood vessels and the formation of foam cells by reducing the protein expression of SR-A.

OBJECTIVE: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. METHODS: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. RESULTS: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. CONCLUSION The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Data Collection ; Humans ; Rabies/prevention & control* ; Rabies Vaccines/adverse effects* ; Rabies virus/genetics*

This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-β(TGF-β) and interleukin-6(IL-6) levels. The protein expression of TGF-β, IL-1β and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 μg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-β and IL-1β, and Western blot was employed to determine the protein levels of TGF-β and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-β and IL-6 levels, down-regulated the protein levels of TGF-β, IL-1β, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-β and IL-6 as well as the mRNA level of TGF-β in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-β signaling pathway.
Animals ; Bronchitis, Chronic/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Inflammation ; Lung ; Poaceae/chemistry* ; Rats ; Rats, Sprague-Dawley ; Rhizome ; Signal Transduction ; Transforming Growth Factor beta/genetics*

BackgroundPostmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS.

MethodsThis was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis.

ResultsA total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E'; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E' to the late diastolic mitral annular velocity (E'/A'; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E' (E/E'; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E' (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E'/A' (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E' (r = 0.472; P = 0.003) and E'/A' (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E' (r = -0.590; P < 0.001), E/E' (r = 0.454; P = 0.004), and E'/A' (r = -0.377; P = 0.018).

ConclusionsConventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD.

Chinese Clinical Trial RegisterChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.