At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*

Objective:To determine the content of the released nickel ion through the 7 extraction media to extract the Ni-Ti wires and to plot the curve of the released nickel ion so as to identify a leaching medium that can be substituted for blood for in vitro Ni release evaluation. Methods:The release of Ni through microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) in the goat serum was determined. Because of the high content of Ni release, it could be determined by diluting the extraction medium, and other extraction media could be determined directly. Ni release standard curves were plotted by the release amount and different time point variables. Though the different extraction media Ni release curves confirm the specificity of extraction media instead of blood.Results:By analyzing the Ni release curves of seven leaching media, it was found that none of these seven extraction media was suitable for the evaluation of Ni release in in vitro leaching media. Considering the safety of the leaching medium and the simplicity of preparation, hydrochloric acid solution was chosen as the leaching medium, but the concentration needed to be diluted accordingly. Finally, a hydrochloric acid solution was created as an alternative to blood for the in vitro study of Ni release from Ni-Ti alloy cardiovascular products, with a volume fraction of 0.005%. Conclusions:The in vitro leaching medium that can replace blood was found to be hydrochloric acid for the time being, but its concentration was too high, resulting in too much Ni release as well, which deviated from the actual situation. Therefore, the hydrochloric acid solution was diluted step by step, and the Ni release curve was examined until it was close to the clinical release level, and the actual concentration was determined, thus laying a solid foundation for the subsequent evaluation of the safety and risk.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

Objective To investigate the hemodynamic characteristics of carotid artery models with different degrees of artificial arterial stenosis based on hemodynamic numerical simulation,and to analyze causes of internal carotid artery stenosis and the diseases due to the stenosis from the perspective of hemodynamics.Methods Two-dimensional CT data of healthy individuals were collected from Affiliated Hospital of Inner Mongolia Minzu University,and the three-dimensional model of carotid artery was reconstructed from the two-dimensional CT data using medical modeling software MIMICS20.0.Subsequently,the obtained carotid artery model was imported to 3-Matic Medical software and interfered with various degrees of artificial internal carotid artery stenosis at the same location to obtain the models with 25%,50%and 75%internal carotid artery stenosis.After format conversion,boundary condition setting and mesh generation,the models were imported to computational fluid dynamics software FLUENT14.5 for the hemodynamic numerical simulation and analysis of the carotid artery and two-phase blood flow.Results The comparison of the blood streamlines and velocity vector maps of 3 different degrees of internal carotid artery stenosis at the same location revealed that with the increase of stenosis severity,the phenomenon of blood vortex flow at the carotid sinus decreases rapidly,but obvious vortex flow appeared above and below the internal carotid artery stenosis,and the blood flow was selectively deflected.During the internal carotid artery stenosis from 25%to 50%and then to 75%,the pressure on the wall of internal carotid artery was always low,and the pressure on the wall of internal carotid artery was gradually increased,forming a high pressure area.There was high shear stress area at the stenosis,and the low shear stress ranges above and below the stenosis were obviously larger.Conclusion The technology of using computer software to obtain models with artificial stenosis is convenient and efficient.When the internal carotid artery stenosis increases from 25%to 50%and then to 75%,the blood flow of the carotid artery changes obviously,obvious vortex flow appears in the internal carotid artery,and the mechanical properties of the wall of the carotid artery also change.

ObjectiveTo investigate the pharmacological effect and metabolic mechanism of Linderae Radix on the intrauterine adhesion （IUA） rat model. MethodAn IUA rat model was induced by mechanical injury and infection. Molecular biology and pharmacology techniques were employed to evaluate the inhibitory effect of Linderae Radix extract （LAE） on fibrosis in IUA. Serum metabolomics analysis based on gas chromatography-mass spectrometry （GC-MS） was conducted to explore the metabolic regulation mechanism of LAE. ResultAnimal experiments showed that LAE significantly improved the morphology and structural damage of uterine tissue cells in the IUA rat model， promoted endometrial proliferation， vascular regeneration， and morphological recovery， inhibited the mRNA expression of transforming growth factor-β₁ （TGF-β₁）， Smad2， and Smad3， and increased the expression of Smad7 mRNA to suppress fibrosis. Additionally， LAE significantly suppressed the levels of estrogen （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and tumor necrosis factor-α （TNF-α） expression （P<0.01）， thereby improving the uterine microenvironment. Metabolomics analysis revealed significant metabolic abnormalities in the serum of IUA rats compared with the results in the normal group， and nine differential metabolites were identified. LAE effectively ameliorated these metabolic abnormalities， primarily by influencing six differential metabolites， including five shared metabolites among the nine identified markers： L-aspartic acid， L-pyroglutamic acid， L-serine， glucose， and L-norvaline. Pathway enrichment analysis indicated that the aminoacyl-tRNA biosynthesis pathway was the main affecting mechanism. ConclusionIn combination with the pharmacological research results， LAE effectively improved uterine damage and inhibited fibrosis in the IUA rat model. Its mechanism may involve the inhibition of the aminoacyl-tRNA biosynthesis pathway and the improvement of the microenvironment.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

OBJECTIVE To study the imp rovement effects of total flavonoids of Psidium guajava leaves on myocardial hypertrophy in hypertensive model rats. METHODS Ten rats were randomly selected from 60 healthy SD rats as the normal group ； other 50 rats established hypertensive model ，and 44 rats with successful modeling were randomly divided into model group ， anisomycin group [p38 mitogen-activated protein kinase （p38 MAPK）activator，1 mg/kg]，total flavonoids of P. guajava leaves+ anisomycin group （200 mg/kg total flavonoids+ 1 mg/kg anisomycin ）and total flavonoids of P. guajava leaves group （200 mg/kg） by random volume mass ranking method ，with 11 rats in each group. Rats in normal group and model group were given 3％ hydroxymethylcellulose sodium solution ，and other groups were given relevant solution intragastrically ，once a day ，for consecutive 6 weeks. Blood pressure （systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ），cardiac index and left ventricular index were measured. The levels of tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）and IL- 6 in myocardial tissue were detected. The pathomorphological changes of myocardial tissue were observed. The expression of p 38 MAPK， phosphorylated p 38 MAPK （p-p38 MAPK），extracellular regulated protein kinase 1/2 （ERK1/2），phosphorylated ERK 1/2 （p-ERK1/2），c-Jun N-terminal kinase （JNK）and phosphorylated JNK （p-JNK）in myocardial tissue were detected. RESULTS Compared with normal group ，the systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ，cardiac index ，left ventricular index as well as the levels of TNF-α，IL-1β and IL-6 and protein expression of p-p 38 MAPK，p-ERK1/2 and p-JNK in myocardial tissue were increased significantly in anisomycin group and model group （P＜0.05）；it was also found that hypertrophy of cardiomyocytes ，disorder of myocardial fibers ，looseness，edema and proliferation of connective tissue between myocardial fibers，increased infiltration of inflammatory cells ，etc. Compared with anisomycin group and model group ，the le vels of above indexes in total flavonoids of P. guajava leaves+ anisomycin group and total flavonoids of P. guajava leaves group were decreased significantly （P＜0.05）； cardiomyocytes were 163.com slightly larger and arranged reasonably ；the degree of myocardial hypertrophy，looseness，edema and proliferation of connective tissue were relieved ，and the improvement effect of total flavonoids of P. guajava leaves group was more significant （P＜0.05）. CONCLUSIONS The total flavonoids of P. guajava leaves can reduce blood pressure and improve myocardial hypertrophy in hypertensive model rats. Its mechanism may be related to the inhibition of p38 MAPK signal pathway activity and the expression of inflammatory factors.

Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1β,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1β(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1β(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1β(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.
Animals ; Humans ; Mice ; Disease Models, Animal ; Exosomes/pathology* ; Interleukin-10/metabolism* ; Macrophages ; Mesenchymal Stem Cells ; Mice, Inbred C57BL ; MicroRNAs/genetics* ; Myocardial Reperfusion Injury ; Osteogenesis ; Stroke Volume ; Tumor Necrosis Factor-alpha/metabolism* ; Umbilical Cord/pathology* ; Ventricular Function, Left

Objective:To analyze the clinical features of bronchiectasis in children after severe adenovirus pneumonia and to provide clinical clues for the early diagnosis of bronchiectasis in children after severe adenovirus pneumonia.Methods:A retrospective study was made to analyze the clinical data of 26 children with bronchiectasis after severe adenovirus pneumonia treated in Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from May 2016 to May 2021.Results:A total of 26 cases were reported, including 18 males and 8 females.The median onset age of severe adenovirus pneumonia was 23.0 (15.0, 48.0) months.A total of 23 cases suffered concurrent infections, and bacterial co-infection was the most common (16 cases). High resolution computed tomography (HRCT) showed multiple lobar solids in the lung with/without pleural effusion.During the acute phase, most of the cases were treated with intravenous immunoglobulin (21 cases), mechanical ventilation (20 cases), and systemic glucocorticoids (19 cases). The median age at diagnosis of bronchiectasis was 29.5 (21.0, 56.8) months, and the median time that the patients took to develop into acute adenovirus pneumonia was 6.0 (3.3, 13.0) months.Six cases suffered bronchiectasis alone, and 20 cases had bronchiectasis combined with post-infectious bronchiolitis obliterans (PIBO). Of these 20 cases, 3 cases developed bronchiectasis and PIBO simultaneously, and the remaining 17 cases developed bronchiectasis after PIBO.In the included 26 cases, diffuse bronchiectasis predominated (24 cases), most frequently involving the left lower lobes (21 cases) and right lower lobes (21 cases). Cylindrical bronchiectasis was the most common type (23 cases). All the patients had recurrent cough and wheezing during follow-up, and only 3 cases coughed up pus sputum without hemoptysis.All children had acute exacerbations, which were mostly caused by bacteria (21 cases). Nineteen cases combined with PIBO and 1 case with only bronchiectasis were rehospitalized.There was no cases of surgical resection or death.Conclusions:Bronchiectasis after severe adenovirus pneumonia mostly occurs in patients with or without PIBO.Multiple lobe involvement and co-infection may be a risk factor for PIBO patients to develop bronchiectasis.The clinical manifestations are mostly recurrent cough and wheezing, while sputum and hemoptysis are less common.Pediatricians should promptly perform chest HRCT for early diagnosis of the disease.

Objective:To observe preventive effect of intestinal stent against anastomotic leakage after rectal cancer operation.Methods:A retrospective cohort study was carried out. Clinical data of 107 patients with low rectal cancer undergoing laparoscopic radical resection from January 2015 to August 2019 were retrospectively analyzed. Intestinal stent was placed intraoperatively in 48 cases and was not placed in 59 cases. Postoperative Wexner score for anal function and incidence of anastomotic leakage were compared between patients with and without intstinal stent.Results:There was no significant differences in age, distance between tumor and the anal verge, operative time and postoperative Wexner score for anal function between the two groups (all P>0.05). After a month of follow-up, the incidence of anastomotic leakage was 16.9% (10/59) in the non-stent group, while no anastomotic leakage was found in the stent group ( P=0.002). Conclusion:Placement of intestinal stent can effectively prevent anastomotic leakage after low rectal cancer surgery.