Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Background and purpose:Despite the significant advancements that have been made in the treatment of gastric cancer,there are still problems such as poor prognosis and low five-year survival rate in advanced gastric cancer.Therefore,exploring effective treatment options remains a key focus of clinical research.As a new type of immune checkpoint inhibitor,the clinical efficacy and safety of pembrolizumab still need to be confirmed by extensive research.Therefore,this study conducted regression analysis of the effect of pembrolizumab combined with XELOX regimen in the treatment of advanced gastric cancer,providing a reference for clinical treatment.Methods:Clinical data of patients with advanced gastric cancer who were admitted to Shanxi Province Cancer Hospital from March 2020 to August 2022 were retrospectively collected.Inclusion criteria:patients with HER2-negative,untreated advanced gastric cancer or adenocarcinoma of the esophagogastric junction,confirmed by clinical histopathological examination and meeting relevant diagnostic criteria;TNM stage Ⅳ;age≥20 years;expected survival≥6 months;no severe organ damage before treatment;Karnofsky score＞60;patients with complete clinical data.Exclusion criteria:patients with concurrent major organ dysfunction;hypothyroidism or hyperthyroidism;blood or coagulation disorders;autoimmune diseases;lactating or pregnant women;individuals with mental illnesses or a history of mental illness;those with concurrent other malignancies;those with severe liver or kidney dysfunction;patients with incomplete clinical data.Based on the inclusion and exclusion criteria,91 patients with advanced gastric cancer were selected.Among them,45 received XELOX regimen treatment(control group),and 46 received pembrolizumab combined with XELOX regimen treatment(observation group).After establishing the database,one patient in the observation group was found to have logical errors in their treatment information and was therefore excluded.Ultimately,90 patients were included in the study,with 45 in each of the control and observation groups.The efficacy,median overall survival(OS),median progression-free survival(PFS),toxic side effects,improvement in quality of life,and levels of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),Escherichia coli,Bifidobacterium and Lactobacillus before and after treatment were compared between the two groups.This study was approved by the ethics committee of Shanxi Province Cancer Hospital(ethics number:KY2023081).Results:After treatment,the proportion of progressive disease(PD)in the observation group was 20.0%(9/45),which was lower than that in the control group(40.0%,18/45).However,there was no significant difference between the two groups in proportion of stable disease(SD),complete response(CR)and partial response(PR)(P＞0.05).The improvement rate of quality of life in the observation group after treatment was 60.0%(27/45),which was higher than that in the control group,with a rate of 37.8%(17/45)(P＜0.05).The median OS and PFS in the observation group were longer compared with the control group(P＜0.05).After treatment,the levels of CEA and CA19-9 in peripheral blood of the observation group were lower compared with the control group(P＜0.05).After treatment,the number of Escherichia coli was lower in the observation group than in the control group,while the numbers of Bifidobacterium and Lactobacillus were higher(P＜0.05).There was no significant difference in the incidence of nausea and vomiting,diarrhea,leukopenia,rash,liver function damage between the two groups(P＞0.05).Conclusion:The combination of pembrolizumab and XELOX regimen can regulate the expression levels of tumor markers in patients with advanced gastric cancer,prevent disease progression,improve patient quality of life,and help maintain intestinal microecology balance.

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

Objective To explore the diagnostic value of artificial intelligence (AI) cytology combined with DNA-image cytometry (DNA-ICM) auxiliary diagnostic system for the identification of benign and malignant pleural effusion and ascites. Methods Liquid-based cytology technology (LCT), DNA-ICM, AI, and AI combined with DNA-ICM were used to identify benign and malignant pleural effusion and ascites specimens in 360 cases, and their sensitivity, specificity, accuracy, Kappa value, Youden index and AUC were statistically analyzed. Results The sensitivity, specificity, and accuracy of AI combined with DNA-ICM in detecting benign and malignant pleural effusion and ascites were 95.23%, 94.12%, and 94.44%, respectively, which were higher than those of the three other separate detection methods (all P < 0.05). The kappa values of LCT, DNA-ICM, and AI were 0.646, 0.642, and 0.586; their Youden index values were 0.693, 0.687, and 0.676, and their AUC values were 0.846, 0.843, and 0.838, respectively. The Kappa value of AI combined with DNA-ICM was 0.869, the Youden index was 0.893, and AUC was 0.947, which were all higher than those of the three detection methods alone. Conclusion Among the three separate detection methods, LCT has the highest reliability, authenticity, and diagnostic value, and it can be used as a common method for the clinical identification of benign and malignant pleural effusion and ascites. The diagnostic performance of AI combined with DNA-ICM auxiliary diagnosis system in identifying benign and malignant pleural effusion and ascites is better than those of the three separate detection methods and can be used as a reliable method for the clinical identification of benign and malignant pleural effusion and ascites.

Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

Objective:To explore the effect of acute kidney injury(AKI)on near-term survival after lung transplantation(LT)in patients with idiopathic pulmonary fibrosis(IPF).Methods:Through consulting electronic medical records, anesthetic modes and Chinese Lung Transplant Registration System, clinical data are retrospectively reviewed for 275 IPF patients undergoing LT at Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2017 to April 2021.According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes(KDIGO), they are divided into two groups of AKI(169 cases)and non-AKI(106 cases).Perioperative findings of two groups are recorded.Then univariate and multivariate Cox regression models are employed for determining whether or not inter-group differences existed in survival rates post-LT.Also AKI is staged according to the KDIGO.And the effect of stage 1/2/3 AKI on near-term postoperative prognosis is examined.Results:The differences are significantly different in recipient gender, creatinine, 6-minute walking test, forced vital capacity(FVC), lung allocation score, oxygenation index, N-terminal pro-brain natriuretic peptide(NT-Pro BNP), preoperative hormone use and volume of crystal infusion( P<0.05).After multivariate Cox regression correcting for covariates, no statistical significance exists in effect of AKI stage 1 on near-term postoperative survival rate( P<0.05).AKI stage 2/3 still has statistical significance in risk of mortality at Day 30/90/180/365 post-operation( P>0.05). Conclusions:As a common complication post-LT, AKI significantly affects near-term postoperative prognosis of transplant IPF patients.Stage 2/3 AKI impacts near-term postoperative survival while stage 1 AKI is not associated with higher mortality.

OBJECTIVE To explore the effects of pterostilbene （PTE） on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group； after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back， model rats were randomly divided into model group， PTE low-dose group （40 mg/kg）， PTE high-dose group （80 mg/kg）， PTE high-dose+PP2 group （80 mg/kg PTE+2 mg/kg SRC inhibitor PP2）， with 10 rats in each group. On the second day after modeling， the rats in each drug group were intraperitoneally injected with corresponding drug solutions， while the rats in control group and model group were intraperitoneally injected with normal saline， once a day， for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration； the contents of interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in the serum of rats were detected； the pathological changes of wound granulation tissue were observed， and the expressions of SRC/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group， the wound healing rate， serum content of VEGF， the phosphorylation levels of SRC， MEK1/2 and ERK1/2 were decreased significantly （P＜0.05）， while serum contents of IL- 1β， IL-6 and TNF-α were increased significantly （P＜0.05）； there was obvious infiltration of inflammatory cells in the wound granulation tissue， and the number of new blood vessels decreased. Compared with model group， above indexes of PTE low-dose and high-dose groups were improved significantly （P＜0.05）， and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes （P＜0.05）. CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats， the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.

Objective : To detect the expression of protein arginine methyltransferase 5 (PRMT5) in gastric cancer tissues and gastric cancer cells , and to investigate the regulation of PRMT5 on the proliferation , migration , invasion and epithelial mesenchymal transition (EMT) of gastric cancer cells. Methods : ① The expression of PRMT5 in pathological tissues of chronic non⁃atrophic gastritis , and pregastric cancer, including chronic atrophic gastritis and intestinal metaplasia , and early gastric cancer was analyzed based on Bioinformatics Analysis by GEO database. Ualcan and HPA databases were employed to analyze the expression of PRMT5 in gastric cancer tissues. The expression of PRMT5 in gastric cancer cells was detected by Western blot. ② The expression of PRMT5 in gastric cancer cells was regulated by plasmid , and its efficiency was verified by Western blot and RT⁃PCR. The protein expression of PRMT5 in gastric cancer cells was analyzed via Western blot. The abilities of migration and invasion were examined by scratch assay , Transwell and BD Matrigel invasion assays. Clone formation assay and CCK⁃8 assay were used to examine the proliferation of gastric cancer cells. ③ The expression of interstitial⁃related proteins and epithelial⁃related proteins was evaluated via Western blot. Results : GEO database found that PRMT5 expression increased gradually in chronic non⁃atrophic gastritis , precancerous lesions and early gastric cancer. Ualcan andHPA databases found that PRMT5 in gastric cancer tissues were higher than that in normal gastric tissues both at the HPA databases found that PRMT5 in gastric cancer tissues were higher than that in normal gastric tissues both at the mRNA and protein levels. PRMT5 upregulation elevated the migration , invasion and proliferation of gastric cancer cells , while PRMT5 downregulation inhibited those. In addition , PRMT5 upregulation raised the expression of interstitial⁃related proteins and decreased the expression of epithelial⁃related proteins while PRMT5 downregulation was the opposite. Conclusion PRMT5 is relatively highly expressed in gastric cancer tissues. Furthermore , PRMT5 can enhance the migration , invasion and proliferation ability of gastric cancer cells , and promote EMT in gastric cancer.

OBJECTIVE: To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C ₂ segment. METHODS: The literature about the surgery for cervical OPLL involving C ₂ segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized. RESULTS: For cervical OPLL involving the C ₂ segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification. CONCLUSION OPLL involving the C ₂ segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C ₂ segment.
Humans ; Longitudinal Ligaments/surgery* ; Ossification of Posterior Longitudinal Ligament/surgery* ; Treatment Outcome ; Osteogenesis ; Decompression, Surgical/methods* ; Cervical Vertebrae/surgery* ; Laminoplasty/methods* ; Kyphosis/surgery* ; Retrospective Studies

Objective:To explore the early prognosis on patient of idiopathic pulmonary fibrosis (IPF) combined with different degrees of pulmonary arterial hypertension (PAH) undertake lung transplantation (LTx).Methods:From January 2017 to December 2020, the clinical data of 134 patients with IPF who underwent LTx in Wuxi People's Hospital were analyzed retrospectively. According to the average pulmonary artery pressure detected by right cardiac catheter before operation, the patients were divided into mild PAH group (63 cases), moderate PAH group (47 cases) and severe PAH group (24 cases). The donor data and the recipient's preoperative, intraoperative and postoperative data were collected; the postoperative survival curve to analyze early survival among the three patient groups.Results:With the increase of pulmonary artery pressure, the rate of abnormal right ventricular function increased, the end diastolic diameter of left ventricle decreased before operation, and the rate of using veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increased during the surgery ( P<0.05). Multivariate analysis found that combined severe PAH had significant effects on primary graft dysfunction (Primary graft dysfunction, PGD), retracheal intubation or tracheotomy, hypovolemic shock within 72 h, and 6-month survival after LTx. The survival surve showed that 30-day survival rates of patients with IPF complicated with mild, moderate and severe PAH were 85.7%, 80.8% and 66.7% respectively, and the 6-month survival rates were 80.9%, 74.0% and 62.2%, respectively. Conclusion:Patient of IPF combined with different degrees of PAH had a significant impact on cardiac function and intraoperative ECMO selection of LTx, and severe PAH could significantly reduce the early survival rate after LTx.