Objective To explore the distribution of traditional Chinese medicine(TCM)syndrome elements in patients with multi-drug resistant bacteria-infected pneumonia.Methods Clinical data of 126 patients with multi-drug resistant bacteria-infected pneumonia admitted to the intensive care unit of Lung Disease Centre of Qingdao Hospital of Traditional Chinese Medicine from May 2020 to July 2022 were retrospectively collected.The clinical data included the patients'gender,age,underlying diseases,history of bad additions of smoking and alcohol,multi-drug resistant bacteria,and the information of four diagnostic methods of TCM,etc.The disease-nature syndrome elements in patients with drug-resistance to various strains of drug-resistant bacteria were extracted,and then deficiency-excess syndrome differentiation was carried out.Results(1)A total of 201 strains of multi-drug resistant bacteria were detected in 126 patients with multi-drug resistant bacterial pneumonia.The main pathogenic species were Gram-negative bacteria,and the proportion accounted for 95.52%(192/201),which was significantly higher than that of Gram-positive bacteria[4.48%(9/201)],with a statistically significant difference(χ2 = 166.612,P＜0.001).Klebsiella pneumoniae accounted for the highest percentage of 23.38%in the gram-negative bacterium.(2)A total of 12 syndrome elements were extracted from the 126 patients.The excess syndrome elements were predominated by phlegm and heat,and the deficiency syndrome elements were predominated by yin deficiency.There was no statistically significant difference in the distribution of yin deficiency,blood deficiency,heat,phlegm,fluid-retention and damp syndrome elements among patients with different strains of drug-resistant bacterial infection(P＞0.05).(3)Of the 126 patients,62 cases(49.21%)had simple excess syndrome,one case(0.79%)had simple deficiency syndrome,and 63 cases(50.00%)had concurrent deficiency-excess syndrome.Among the 126 patients,there were 19 cases of single syndrome element,41 cases of concurrent two-syndrome element,49 cases of concurrent three-syndrome element,16 cases of concurrent four-syndrome element,and one case of concurrent five-syndrome element.And the combined syndrome element of phlegm-heat-yin deficiency occurred most frequently for 26 times.Conclusion Gram-negative bacteria are the primary infectious pathogens for the patients with multi-drug resistant bacterial infections,and the TCM syndrome elements of the patients are characterized by the concurrence of deficiency and excess and simple excess syndrome,mainly manifesting as phlegm,heat,and yin deficiency.

Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

Biomarkers, Tumor ; Humans ; Sarcoma, Synovial/surgery* ; Stomach

Objective To investigate the protective effect and mechanism of polydatin ( PD) on allergic rhinitis (AH) by regulating mitophagy through PINK1- Parkin signaling pathway, and to provide a new target for clinical treatment of AH.Methods Thirty-two BALB/c murine were randomly divided into 4 groups: control group, OVA group, PD low-dose (30 mg • kg 1 ) and high-dose ( 45 mg • kg 1 ) treatment groups.At the end of modeling, the total number of sneezing and nasal nibbing of murine was recorded.HE staining was used to observe the morphology of na- sal mucosal epithelium and eosinophil infiltration.Western blot was used to detect the expression of P1NK1 , Parkin, TOM20 and mitochondrial apoptosis- related proteins Bax, Bcl-2, caspase-3, cleaved- caspase-3 and Cytochrome C.Hie expression of P1NK1 and cleaved-caspase-3 in nasal epithelial cells (HNEpC) was observed by immunofluorescence.Re¬sults The frequency of sneezing and nasal rubbing movements was significantly increased, the nasal mu¬cosa epithelium was thickened, and eosinophils were accumulated in AH murine , these results were reversed after PD treatment.Western blot results shower] that signaling proteins PINK1/Parkin anrl pro-apoptotie pro¬teins, including Bax, caspase-3, cleaved-caspase-3 and Cytochrome C were significantly overexpressed, the expression of TOM20 and Bcl-2 was decreased in OVA group, and PD up-regulated the levels of P1NK1 , Parkin, as well as Bcl-2 and inhibited the expression of TDM20 and pro-apoptotic proteins, while after pre- treatment with mitochondrial division inhibitor 1 ( Mdi- vi-1 ) , the expression of P1NK1 and Parkin was re¬duced , the expression of TOM20 was increased, while PD treatment did not significantly affect this effect.From the immunofluorescence results, it can be seen that the level of P1NK1 was increased after IL-13 stim¬ulation of HNEpCs compared with the control group, and PD further up-regulated the expression of P1NK1 , which was suppressed after pretreatment with Mdivi-1 , while PD did not change this phenomenon.Western blot results for P1NK1 and cleaved-caspase-3 were con¬firmed by immunofluorescence.Conclusion PD may activate mitophagy through the P1NK1 -Parkin signaling pathway, thereby protecting against AR.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

BACKGROUND: The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer. METHODS: Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes. RESULTS: Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group. CONCLUSIONS Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.
Humans ; Neoadjuvant Therapy ; Stomach Neoplasms/surgery* ; Treatment Outcome

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of dedifferentiated liposarcomas with meningothelial-like whorls(DDLMW). Methods: Six cases of DDLMW diagnosed at Jiangsu Province Hospital(the First Affiliated Hospital of Nanjing Medical University) from March 2012 to August 2018 were enrolled. The cases were analyzed by routine HE staining, immunohistochemistry(MDM2, CDK4 and p16) and fluorescent in-situ hybridization(FISH) on MDM2 gene. Related literatures were also reviewed. Results: Three of the 6 patients were male.The patient ages ranged from 40 to 77 years (mean, 58 years). Four tumors occurred in the retroperitoneum and two in the mediastinum. Histologically, the tumors showed, in addition to foci of well-differentied liposarcoma, characteristic, scattered meningothelial-like concentrical whorls. The whorls were composed of tightly, concentrically arranged, spindle to ovoid cells with mild to mederate cytological atypia. Metaplastic bone was present within or in their immediate vicinity in four case. The tumors cell also showed strong and diffuse immunoreactivity to MDM2, CDK4 and p16, but no immunoreactivity to S-100 protein, SMA, SOX10, EMA, CD21, CD23 or CD35. The Ki-67 labeling indexes were low, while FISH showed high levels of MDM2 amplification in all cases. Conclusions DDLMW is a rare morphologic variant of dedifferentiated liposarcoma. The whorls in DDLMW do not represent perineurial or follicular dendritic differentiation. Recognition and familiarity with its existence, as well as combined application of immunohistochemical staining and MDM FISH, are important to avoid confusion with other lesions.

【Objective】 To study the mechanisms and therapeutic effects of human olfactory mucosa-derived mesenchymal stem cells（OMSC）on experimental autoimmune encephalomyelitis（EAE）in mice.【Methods】Under local anesthesia by using nasal endoscopy，olfactory epithelia of healthy donors were obtained，digested and cultured up to the 5th passage. OMSC were identified，differentiated and stained. EAE models were induced in C57 female mice by myelin oligodendrocyte glycoprotein（MOG35- 55）and pertussis toxin（PT）. Neurological function was documented daily. On day 16 after immunization（peak of incidence），the mice were divided randomly into two groups and treated with OMSC and PBS via tail vein injection respectively. On day 24 after immunization ，blood was collected from angular vein and levels of IL-10，IL-17，IFN-γ and IL-6 were determined by cytometric beads array（CBA）. The size of the spinal cord lesion in mice was observed and measured by using HE and LFB staining. Peripheral blood lymphocytes（PBL）of healthy donors were obtained and then co-cultured with OMSC. The proportions of CD4+ T cells secreting IFN- γ（Th1 cells）in lymphocyte group and co-culture group were compared after 2 days of cultivation. Adding IDO or COX pathway inhibitor to co- culture group and cultivating for 2 days，we observed and compared the proportions of Th1 cells in lymphocyte group，co-culture group and inhibitor treatment group respectively.【Results】OMSC exhibited certain mesenchymal stem cell-like characteristics with respect to expression of stem cell surface markers and multilineage differentiation potentials. After induced by MOG35- 55 and PT，EAE models showed different levels of neurological damage. Compared with those in PBS treatment group，in OMSC treatment group，the severity of neural dysfunction in mice was significantly reduced（P =0.002），the level of IFN-γ in serum was lower（P = 0.032），but no significant differences in the levels of IL-10，IL-17 and IL-6 were found between two groups. HE and LFB staining revealed that the inflammatory infiltration and demyelinating areas in OMSC treatment group were less than those in PBS treatment group. The proportion of Th1 cells was lower in co-culture group than that in lymphocyte group（P = 0.001），higher in IDO inhibitor group than that in co-culture group（P = 0.01），but no significant difference was found between IDO inhibitor group and lymphocyte group or between COX inhibitor group and co-culture group.【Conclusions】OMSC may regulate the proportion of Th1 lymphocytes through IDO pathway so as to inhibit the demyelinating injuries of EAE in mice. This study provides a new idea for the clinical treatment of multiple sclerosis.