Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

OBJECTIVE: Peritoneal dialysis(PD)-associated peritonitis is a common and major complication of PD and the most common cause of technical failure of PD. The presence of bacterial biofilm may be an important factor leading to refractory or recurrence of peritonitis. To investigate the formation and characteristics of bacterial biofilms on PD catheters after peritonitis-associated catheter removal. METHODS: The patients with maintenance PD who were regularly followed up in the Peking University People' s Hospital from June 2007 to January 2022 were retrospectively analyzed. The patients who withdrew from PD because of peritonitis and removed the PD catheter in our hospital and underwent the scanning electron microscope examination of the catheter were selected. The general information of the patients, the electron microscope results of the PD catheter and the bacterial culture results of the PD fluid were summarized. RESULTS: (1) A total of 18 patients were included, 11 were female (accounting for 61.1%). The average age of the patients was (59.1±11.5) years, and the average duration of dialysis was (80.1±47.4) months. Primary kidney diseases were predominantly chronic glomerulonephritis (55.6%), followed by diabetic nephropathy (27.8%), and others (16.6%). The reasons for catheters removal in 18 patients were refractory peritonitis in 11 cases, recurrent peritonitis in 5 cases, and fungal peritonitis in 2 cases. (2) 16 of the 18 patients (88.9%) had catheter bacterial biofilm, and the bacterial biofilm forms were all cocci. Some were arranged in grape-like shapes, and their diameters ranged from about 500 nm to 1 000 nm. The bacterial culture results of peritoneal dialysis fluid showed that the three most common pathogens were Escherichia coli, methicillin-sensitive Staphylococcus aureus (MSSA), and Staphylococcus epidermidis. (3) Among the 18 patients enrolled, 13 patients (72.2%) had peritonitis in the past. The causative bacteria of peritonitis in 9 patients were cocci, including coagulase-negative Staphylococci (Staphylococcus suis, Staphylococcus surface, Staphylococcus xylosus, Staphylococcus warneri), Staphylococcus aureus, Streptococcus (Streptococcus salivarius and Aerococus viridans). CONCLUSION Bacterial biofilm formation on the inner surface of PD catheter is common in peritonitis-associated catheter removal patients. Not all PD catheters removed due to peritonitis have bacterial biofilms. Bacterial biofilms and peritonitis pathogens may not be consistent.
Humans ; Biofilms/growth & development* ; Peritonitis/etiology* ; Peritoneal Dialysis/instrumentation* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Catheters, Indwelling/microbiology* ; Device Removal ; Catheter-Related Infections/microbiology* ; Aged ; Adult

Diffuse large B-cell lymphoma (DLBCL) can be caused by multiple factors, including virus and autoimmune function, which in turn trigger persistent activation of the B-cell receptor (BCR) signaling pathway and other related signaling pathways, which collectively promote malignant B-cell proliferation and lead to tumor formation. Studies have shown significant progress in the treatment of primary and relapsed/refractory DLBCL with Bruton tyrosine kinase inhibitor (BTKi) in combination with chemotherapy, immunotherapy and small molecule inhibitors in the setting of poor outcome with BTKi monotherapy. This article reviews the progress of BTKi combined regimens in DLBCL.

Objective To construct machine learning models that can be used to predict AUC fold change(FC)using a database of existing pharmacokinetic(PK)and drug-drug interaction(DDI)information,which can be used to explore the possibility of predicting existing drug interactions and to provide certain rational recommendations for clinical drug use.Methods PK data of DDIs and AUC fold change data were extracted from FDA-approved drug labels.Peptide and pharmacodynamic(PD)information related to drug interactions were retrieved through DrugBank,and PPDT identification of relevant peptide IDs was performed using Protein Resource(UniProt),and a matrix normalization code was used to generate multidimensional vector data that were easy to analysis.The effect of PPDT on the AUC,and the resulting multiplicity change was used as the dependent variable for machine learning model construction.The model with the smallest root mean square error(RMES)value was used for model construction to train a bagged decision tree(Bagged)prediction model.The models were tested using the trained models for some of the drug tests.The models were evaluated by reviewing the available literature findings on detection of drug interaction pairs and analyzing and comparing the predicted values.Results A total of 16 pairs of model drug pairs were tested for the effects of 16 drugs on tacrolimus,and it was found that the accuracy of the prediction of the presence or absence of drug interactions was 81.25％;the prediction results were classified according to the FDA standard classification of the strong and weak for the strength of drug interactions,and the results showed that the prediction of the strength of drug interactions,with a large deviation from the larger prediction was less.Conclusion The evaluation of the model to predict the presence or absence of drug interactions was general;however,after classifying the strengths and weaknesses of drug interactions,the prediction of drug interactions was better,and the prediction results indicated that the model prediction performance has a certain reference value for potential DDI assessment before clinical trials.

Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.