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

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Objective:To explore the clinical efficacy of operative treatment of geriatric pelvic fractures.Methods:A retrospective study was conducted to analyze the clinical data of 55 geriatric patients with pelvic fracture who had been operatively treated at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from January 2020 to October 2023. There were 13 males and 42 females with an age of 72.0 (68.0, 83.3) years. By the AO/OTA classification, there were 47 cases of type B and 8 cases of type C; by the classification for fragility fractures of pelvis, there were 5 cases of type Ⅱ, 44 cases of type Ⅲ, and 6 cases of type Ⅳ. The patients received operative treatment 4.0 (3.0, 6.3) days after injury. Of the 10 patients treated by open reduction and closed reduction, the posterior ring was fixated by a plate in 7 and by screws in 3, and the anterior ring was fixated by either a plate, an external fixator or a minimally invasive anterior pelvic ring internal fixator except in the 2 cases receiving no fixation. Of the other 45 patients treated by closed reduction and fixation, the posterior ring was all fixated by screws except in the 2 cases receiving no fixation, and the anterior ring was fixated by either screws, an external fixator or a minimally invasive anterior pelvic ring internal fixator except in the 10 cases receiving no fixation. The major peri-operative complications, quality of fracture reduction, mortality, and functional recovery of the pelvis at the last follow-up were recorded.Results:There were no major peri-operative complications. According to the Matta criteria, the quality of fracture reduction was excellent in 31, good in 14, fair in 8 and poor in 2 cases, giving a good to excellent rate of 81.8% (45/55). Fifty-four cases were followed up for (15.4±9.1) months and 1 case was lost to the follow-up. Four cases died within 1 year after operation, giving a mortality of 7.4% (4/54). The modified Majeed score at the last follow-up was 69 (54, 76) for the 46 cases who had been followed up for longer than 4 months; the functional recovery of the pelvis at the last follow-up was rated as excellent in 27 cases, as good in 8 cases and as fair in 11 cases, giving a good to excellent rate of 76.1% (35/46) according to the criteria proposed by the faculty of the writers. The internal fixation failed in 3 cases during the follow-up.Conclusion:For the geriatric pelvic fractures, operative treatment can lead to satisfactory clinical outcomes.

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.

Objective: To investigate the current status and influencing factors of sleep disorders among pregnant women, so as to provide insights into health management during pregnancy. Methods: Pregnant women who underwent prenatal checkups at Hangzhou Obstetrics and Gynecology Hospital from January to October 2023 were selected as subjects, and general data including age, pregnancy period and exercise were collected through questionnaire surveys. Sleep quality, pregnancy stress, anxiety and depression were evaluated using Pittsburgh Sleep Quality Index, Pregnancy Stress Rating Scale, Pregnancy-related Anxiety Scale and Edinburgh Postnatal Depression Scale, respectively. Factors affecting sleep disorders among pregnant women were analyzed using a multivariable logistic regression model. Results: A total of 386 pregnant women was surveyed, with a mean age of (30.28±4.65) years, including 20.47% in the first trimester, 47.93% in the second trimester and 31.61% in the third trimester. Women with anxiety and depression accounted for 14.51% and 21.76%, respectively. Pregnancy stress was mainly moderate, accounting for 51.04%. There were 106 pregnant women with sleep disorders, accounting for 27.46%. Mutivariable logistic regression analysis showed that age (≥35 years, OR=1.656, 95%CI: 1.094-2.503), pregnancy period (third pregnancy, OR=2.097, 95%CI: 1.213-3.621), regular exercise in the past 6 months (OR=0.376, 95%CI: 0.210-0.670), anxiety (OR=2.794, 95%CI: 1.545-5.048), depression (OR=3.501, 95%CI: 1.877-6.529) and pregnancy stress (moderate, OR=1.355, 95%CI: 1.018-1.801; severe, OR=2.538, 95%CI: 1.417-4.540) were the factors affecting sleep disorders among pregnant women. Conclusions Sleep disorders of pregnant women is influenced by age, pregnancy period, pregnancy stress, anxiety, depression and exercise. It is necessary to identify high-risk individuals with sleep disorders early, and to provide psychological intervention and prenatal health guidance.