Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*

This study summarizes the clinical thinking of acupuncture for snoring based on "disharmony qi leads to restlessness". According to the pathological characteristics of qi stagnation and blood stasis, phlegm dampness and internal obstruction in snoring patients, combined with the etiology, pathogenesis and location of the disease, the innovative viewpoint of "disharmony qi leads to restlessness" is proposed. It is believed that the key to snoring treatment lies in "regulating qi ". In clinical practice, acupuncture can directly regulate the qi of the disease's location, regulate the qi of the organs and viscera, and regulate the qi of the meridians to achieve overall regulation of the body's internal and external qi, smooth circulation of qi and blood, and ultimately achieve the therapeutic goal of harmonizing qi, stopping snoring, and improving sleep quality.
Humans ; Qi ; Snoring/therapy* ; Psychomotor Agitation ; Acupuncture Therapy ; Meridians

The article analyzes chief physician SUN Wuquan's empirical characteristics in treating neck-type cervical spondylosis:disease differentiation combined with pattern differentiation,emphasizing the assessment of tendons and bones,with DING's Tuina(Chinese therapeutic massage)manipulations and static Gongfa(Qigong exercise)as the predominant treatment,inherits the academic features of DING's Tuina school,"paying equal attention to tendons and bones,putting function first";thus provides a reference for treating neck-type cervical spondylosis with Tuina therapy.

This study aimed to investigate the curative effect of spiral embedded flap urethroplasty for the treatment of meatal stenosis after penile carcinoma surgery. From January 2015 to January 2021, we used our technique to treat strictures of the external urethral orifice in seven patients, including four cases of meatal stenosis after partial penile resection and three cases of meatal stenosis after perineal stoma. All patients had previously undergone repeat urethral dilatation. The patients underwent spiral embedded flap urethroplasty to enlarge the outer urethral opening. The patients' mean age at the time of surgery was 60 (range: 42-71) years, the mean operative time was 43 min, and the median follow-up period was 18 months. The patients voided well post-operatively, and urinary peak flow rates ranged from 18.3 ml s^-1 to 30.4 ml s^-1. All patients were successful with absence of urethral meatus stricture. The present study showed that using spiral embedded flap urethroplasty to treat meatal stenosis after penile carcinoma surgery is an effective surgical technique with good long-term outcomes.
Male ; Humans ; Urologic Surgical Procedures, Male/methods* ; Penile Neoplasms/surgery* ; Constriction, Pathologic/surgery* ; Treatment Outcome ; Urethral Stricture/surgery* ; Urethra/surgery* ; Amputation, Surgical ; Carcinoma/surgery* ; Retrospective Studies

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

To investigate the effects of intratracheal instillation of PM2.5 suspension on bleomycin (BLM)-induced pulmonary fibrosis in mice and the intervention of neotuberostemonine (NTS), the BLM dose (1.5 or 3.0 U/kg) and PM2.5 frequency (1 or 2 times per week) were studied by factorial experiment design. After intratracheal instillation of BLM (1.5 or 3.0 U/kg) on day 0, PM2.5 (5 mg/kg) was intratracheally injected to mice once or twice a week from day 1 to day 21, and the mice in the treatment group were given 30 mg/kg NTS by gavage once a day from day 8 to day 21. The degree of pulmonary fibrosis was evaluated by lung coefficient, hydroxyproline (HYP) content, HE staining and Masson staining lung sections as well as their semi-quantitative index (HE inflammatory score and collagen volume fraction, CVF). The results showed that the HE scores increased significantly in mice singly given PM2.5 once a week, the HYP content and HE score increased in mice singly given PM2.5 twice a week, but their CVF values did not significantly increase. However, the CVF values increased significantly in mice treated with PM2.5 and BLM co-infusion. These results suggested that PM2.5 (administered singly) could significantly increase BLM-induced collagen deposition and greatly aggravate pulmonary fibrosis although it mainly caused pulmonary inflammation rather than pulmonary fibrosis. NTS could significantly reduce the CVF value and α-SMA protein level of the model mice. It can be concluded that PM2.5 has great influence on patients with respiratory diseases, while NTS can improve pulmonary fibrosis induced by the combination of PM2.5 and BLM.

Objective:To explore the effects of Huatan Tongluo Decoction （HTTLD） on the morphology and function of brain tissues and intestine in rats with cerebral ischemia/reperfusion based on the gut-brain axis. Method:Sixty SPF male rats were randomly divided into a sham operation group， a model group， high- （28.66 g·kg^-1）， medium- （14.33 g·kg^-1）， and low-dose （7.16 g·kg^-1） HTTLD groups， and an edaravone （4 g·kg^-1）+Clostridium butyricum （5.0×10⁸ cfu·mL^-1） group. The model was established by focal cerebral ischemia/reperfusion in rats. The drugs were administered by gavage. The brain tissue injury was determined by neurological deficit score and 2，3，5-triphenyl tetrazolium chloride （TTC） staining. The effect of cerebral ischemia/reperfusion on intestinal motility was assessed by the propulsion rate of small intestine. The intestinal mucosal cell damage was evaluated by the pathomorphological examination of the duodenal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of D-lactate （D-LAC）， diamine oxidase （DAO）， and bacterial endotoxin （lipopolysaccharide， LPS） in serum. Western blot was used to detect the expression of Occludin， Claudin-5， and zonula occludens 1 （ZO-1） in the duodenum. Result:After cerebral ischemia/reperfusion， rats developed neurological deficit symptoms. The neurological deficit score in the model group was higher than that in the sham operation group （P<0.01）. Compared with the model group， the high- and medium-dose HTTLD groups could relieve the symptoms of neurological deficits and lower neurological deficit scores （P<0.01）. The results of TTC staining showed that the model group presented obvious infarcts in brain tissues compared with the sham operation group （P<0.01）. The cerebral infarction volumes of HTTLD groups were reduced compared with that in the model group （P<0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. Furthermore， the propulsion rate of small intestine in the model group was significantly reduced compared with that in the sham operation group （P<0.01）. Compared with the model group， HTTLD groups could increase propulsion rates of small intestine （P<0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. After cerebral ischemia/reperfusion， obvious duodenal mucosal damage could be observed， which was relieved after the administration of HTTLD. Western blot results showed that the protein expression of ZO-1， Occludin， and Claudin-5 in the model group was reduced compared with that in the sham operation group （P<0.01）. Compared with the model group， the HTTLD groups could up-regulate the expression of ZO-1， Occludin， and Claudin-5 to varying degrees （P<0.05， P<0.01）， especially the high-dose HTTLD group. ELISA showed that the serum D-LAC， DAO， and LPS of the model group were elevated compared with those in the sham operation group （P<0.01）. Compared with the model group， the HTTLD groups showed reduced D-LAC and DAO （P<0.05， P<0.01）， and the medium- and high-dose HTTLD groups showed reduced LPS （P<0.05， P<0.01）， especially the high-dose HTTLD group. Conclusion:After cerebral ischemia/reperfusion， the rats showed damaged brain tissues， neurological dysfunction， intestinal mucosal injury， weakened intestinal motility， and destroyed the intestinal mucosal barrier. HTTLD can protect against brain-gut axis injury after cerebral ischemia/reperfusion by reducing the damage on brain tissues and gastrointestinal mucosa， relieving the symptoms of neurological deficits， promoting gastrointestinal motility， improving intestinal barrier function， and reducing the release of intestinal bacterial metabolites or poisons.

Objective:To determine whether glutathione dehydrogenase (GLDH), purine nucleotide phosphorylase (PNP), α-glutathione-S-transferase (α-GST), and arginase 1 (Arg1) can be used as the early biomarkers of drug-induced liver injury by comparing the changes of traditional biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin (TBIL) and potential biomarkers GLDH, PNP, α-GST and Arg1 in acetaminophen (APAP)-induced liver injury model rats. Method:The 48 rats were randomly divided into two groups:blank group and model group. 24 rats in each group, half male and half female. The model group received 1 250 mg·kg^-1 APAP solution by intragastric administration to establish the drug-induced liver injury. 6 rats (half male and half female) were randomly selected from each group at 3, 6,12 and 24 h after APAP was given to the model group, to detect the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST, Arg1 in serum and levels of GLDH, PNP, α-GST, Arg1 in liver tissue homogenate at each time point Histopathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in serum and liver homogenates were significantly increased in model group(P<0.05,P<0.01), indicating that the APAP-induced liver injury model was successfully replicated. GLDH, PNP, α-GST and Arg1 levels in serum and liver tissues of rats in the model group were increased earlier and more significantly than ALT and AST levels. Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of drug-induced liver injury.

Objective:To replicate the animal model of liver injury in rats by using carbon tetrachloride (CCl₄), investigate the dynamic changes of early biomarkers of liver injury, namely glutamate dehydrogenase (GLDH), purine nucleotide phosphorylase(PNP), α-dynamic changes of glutathione-S-transferase (α-GST) and arginase 1(Arg1), and provide experimental evidence for early detection of acute liver injury. Method:Forty-eight Wistar rats were randomly divided into a blank group and a model group. The model group was intraperitoneally injected with 10 mL·kg^-1 10% CCl₄ olive oil solution, fasting but except water. Animals were sacrificed at 3, 6, 12, and 24 h. The serum liver function alanine aminotransferase(ALT), aspartate aminotransferase (AST), bilirubin (TBIL), alkaline phosphatase (ALP) levels, α-GST, Arg1, GLDH, PNP levels, and liver homogenate superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) levels were then detected. Result:As compared with blank group, the levels of ALT, AST, TBIL, α-GST, Arg1, GLDH, PNP and MDA were increased significantly 3 h after administration, and SOD was decreased significantly(P<0.01). After 6,12 h, the levels of ALT, AST, α-GST, ARG-, GLDH, TBIL, ALP and MDA were increased significantly, while GSH and SOD were decreased significantly (P<0.05, P<0.01). After 24 h, the levels of ALT, AST, α-GST, Arg1, TBIL, ALP and MDA were significantly increased, while GSH and SOD were significantly decreased (P<0.01). Conclusion:α-GST, Arg1, GLDH and PNP have better sensitivity than traditional liver function test indicators, and can be used for early detection of liver injury induced by CCl₄ in rats.