Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer / 中华消化外科杂志

Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.

Progressive encephalomyelitis with rigidity and myoclonus: a case report / 中华神经科杂志

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a specific subtype of the stiff-person syndrome, which is rare and difficult to diagnose clinically. A case of PERM in a 66-year-old female with a fluctuating progressive course was reported in this article. She had increased facial muscle tone, pruritus and sensory hypersensitivity mainly in the head and neck, medullary involvement syndrome and bilateral lower limb rigidity as the main clinical manifestations, and a previous history of pulmonary malignancy, thymoma, typeⅠ diabetes and Hashimoto′s thyroiditis. The patient′s serum and cerebrospinal fluid were positive for anti-glutamic acid decarboxylase antibody. The electromyogram showed a large number of motor unit potentials in the trunk and proximal extremities in the quiet state, which were significantly enhanced during spastic episodes, consistent with the electromyographic manifestations of stiff-person syndrome. The final diagnosis was PERM, and immunotherapy including gamma globulin and hormone responded well. PERM is a rare neurological autoimmune disease with atypical early symptoms, which can be easily misdiagnosed, and it requires attention to avoid delaying the diagnosis.

Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing / 中华烧伤杂志

Objective: To explore the heterogeneity and growth factor regulatory network of dermal fibroblasts (dFbs) in mouse full-thickness skin defect wounds based on single-cell RNA sequencing. Methods: The experimental research methods were adopted. The normal skin tissue from 5 healthy 8-week-old male C57BL/6 mice (the same mouse age, sex, and strain below) was harvested, and the wound tissue of another 5 mice with full-thickness skin defect on the back was harvested on post injury day (PID) 7. The cell suspension was obtained by digesting the tissue with collagenase D and DNase Ⅰ, sequencing library was constructed using 10x Genomics platform, and single-cell RNA sequencing was performed by Illumina Novaseq6000 sequencer. The gene expression matrices of cells in the two kinds of tissue were obtained by analysis of Seurat 3.0 program of software R4.1.1, and two-dimensional tSNE plots classified by cell group, cell source, and gene labeling of major cells in skin were used for visual display. According to the existing literature and the CellMarker database searching, the expression of marker genes in the gene expression matrices of cells in the two kinds of tissue was analyzed, and each cell group was numbered and defined. The gene expression matrices and cell clustering information were introduced into CellChat 1.1.3 program of software R4.1.1 to analyze the intercellular communication in the two kinds of tissue and the intercellular communication involving vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) signal pathways in the wound tissue, the relative contribution of each pair of FGF subtypes and FGF receptor (FGFR) subtypes (hereinafter referred to as FGF ligand receptor pairs) to FGF signal network in the two kinds of tissue, and the intercellular communication in the signal pathway of FGF ligand receptor pairs with the top 2 relative contributions in the two kinds of tissue. The normal skin tissue from one healthy mouse was harvested, and the wound tissue of one mouse with full-thickness skin defect on the back was harvested on PID 7. The multiple immunofluorescence staining was performed to detect the expression and distribution of FGF7 protein and its co-localized expression with dipeptidyl peptidase 4 (DPP4), stem cell antigen 1 (SCA1), smooth muscle actin (SMA), and PDGF receptor α (PDGFRα) protein. Results: Both the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7 contained 25 cell groups, but the numbers of cells in each cell group between the two kinds of tissue were different. Genes PDGFRα, platelet endothelial cell adhesion molecule 1, lymphatic endothelial hyaluronic acid receptor 1, receptor protein tyrosine phosphatase C, keratin 10, and keratin 79 all had distinct distributions on two-dimensional tSNE plots, indicating specific cell groups respectively. The 25 cell groups were numbered by C0-C24 and divided into 9 dFb subgroups and 16 non-dFb groups. dFb subgroups included C0 as interstitial progenitor cells, C5 as adipose precursor cells, and C13 as contractile muscle cells related fibroblasts, etc. Non-dFb group included C3 as neutrophils, C8 as T cells, and C18 as erythrocytes, etc. Compared with that of the normal skin tissue of healthy mice, the intercellular communication in the wound tissue of full-thickness skin defected mice on PID 7 was more and denser, and the top 3 cell groups in intercellular communication intensity were dFb subgroups C0, C1, and C2, of which all communicated with other cell groups in the wound tissue. In the wound tissue of full-thickness skin defected mice on PID 7, VEGF signals were mainly sent by the dFb subgroup C0 and received by vascular related cell groups C19 and C21, PDGF signals were mainly sent by peripheral cells C14 and received by multiple dFb subgroups, EGF signals were mainly sent by keratinocyte subgroups C9 and C11 and received by the dFb subgroup C0, and the main sender and receiver of FGF signals were the dFb subgroup C6. In the relative contribution rank of FGF ligand receptor pairs to FGF signal network in the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7, FGF7-FGFR1 was the top 1, and FGF7-FGFR2 or FGF10-FGFR1 was in the second place, respectively; compared with those in the normal skin tissue, there was more intercellular communication in FGF7-FGFR1 signal pathway, while the intercellular communication in FGF7-FGFR2 and FGF10-FGFR1 signal pathways decreased slightly or did not change significantly in the wound tissue; the intercellular communication in FGF7-FGFR1 signal pathway in the wound tissue was stronger than that in FGF7-FGFR2 or FGF10-FGFR1 signal pathway; in the two kinds of tissue, FGF7 signal was mainly sent by dFb subgroups C0, C1, and C2, and received by dFb subgroups C6 and C7. Compared with that in the normal skin tissue of healthy mouse, the expression of FGF7 protein was higher in the wound tissue of full-thickness skin defected mouse on PID 7; in the normal skin tissue, FGF7 protein was mainly expressed in the skin interstitium and also expressed in the white adipose tissue near the dermis layer; in the two kinds of tissue, FGF7 protein was co-localized with DPP4 and SCA1 proteins and expressed in the skin interstitium, co-localized with PDGFRα protein and expressed in dFbs, but was not co-localized with SMA protein, with more co-localized expression of FGF7 in the wound tissue than that in the normal skin tissue. Conclusions: In the process of wound healing of mouse full-thickness skin defect wound, dFbs are highly heterogeneous, act as potential major secretory or receiving cell populations of a variety of growth factors, and have a close and complex relationship with the growth factor signal pathways. FGF7-FGFR1 signal pathway is the main FGF signal pathway in the process of wound healing, which targets and regulates multiple dFb subgroups.

Clinical and electrophysiological profiles in early recognition of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome / 中华医学杂志(英文版)

Background@#The detection of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome at early stage is challenging for neurologists. Since polyneuropathy could be the first manifestation, it could be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). The present study aimed to determine the clinical and electrophysiological features of POEMS syndrome to distinguish from CIDP.@*Methods@#The data of a group of patients with POEMS (n = 17) and patients with CIDP (n = 17) in Zhongshan Hospital Fudan University from January 2015 to September 2017 were analyzed in this retrospective study. The clinical features, neurological symptoms, and electrophysiological findings were compared between the two groups.@*Results@#Clinically, patients with POEMS demonstrated significantly more neuropathic pain in the lower extremities than patients with CIDP (58.8% vs. 11.8%, P = 0.01). Multisystem features like edema, skin change, organomegaly, and thrombocytosis were also pointed towards the diagnosis of POEMS syndrome. Electrophysiologically, terminal latency index (TLI) was significantly higher in patients with POEMS than that in patients with CIDP (median nerve: 0.39 [0.17–0.52] vs. 0.30 (0.07–0.69), Z = –2.413, P = 0.016; ulnar nerve: 0.55 [0.23–0.78] vs. 0.42 [0.12–0.70], Z = –2.034, P = 0.042). Patients with POEMS demonstrated a higher frequency of absent compound muscle action potential of the tibial nerve (52.9% vs. 17.6%, P = 0.031), less conduction block (ulnar nerve: 0 vs. 35.3%, P = 0.018), and less temporal dispersion (median nerve: 17.6% vs. 58.8%, P = 0.032) than CIDP group. The combination of positive serum monoclonal protein and high TLI (if either one or both were present) discriminated POEMS from CIDP with a sensitivity of 94.1% and 47.1% and specificity of 76.5% and 100.0%, respectively.@*Conclusions@#POEMS syndrome could be distinguished from CIDP through typical clinical and electrophysiological characteristics in practice. The combination of serum monoclonal protein and high TLI might raise the sensitivity of detecting POEMS syndrome.

Clinical and electrophysiological profiles in early recognition of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome / 中华医学杂志(英文版)

BACKGROUND@#The detection of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome at early stage is challenging for neurologists. Since polyneuropathy could be the first manifestation, it could be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). The present study aimed to determine the clinical and electrophysiological features of POEMS syndrome to distinguish from CIDP.@*METHODS@#The data of a group of patients with POEMS (n = 17) and patients with CIDP (n = 17) in Zhongshan Hospital Fudan University from January 2015 to September 2017 were analyzed in this retrospective study. The clinical features, neurological symptoms, and electrophysiological findings were compared between the two groups.@*RESULTS@#Clinically, patients with POEMS demonstrated significantly more neuropathic pain in the lower extremities than patients with CIDP (58.8% vs. 11.8%, P = 0.01). Multisystem features like edema, skin change, organomegaly, and thrombocytosis were also pointed towards the diagnosis of POEMS syndrome. Electrophysiologically, terminal latency index (TLI) was significantly higher in patients with POEMS than that in patients with CIDP (median nerve: 0.39 [0.17-0.52] vs. 0.30 (0.07-0.69), Z = -2.413, P = 0.016; ulnar nerve: 0.55 [0.23-0.78] vs. 0.42 [0.12-0.70], Z = -2.034, P = 0.042). Patients with POEMS demonstrated a higher frequency of absent compound muscle action potential of the tibial nerve (52.9% vs. 17.6%, P = 0.031), less conduction block (ulnar nerve: 0 vs. 35.3%, P = 0.018), and less temporal dispersion (median nerve: 17.6% vs. 58.8%, P = 0.032) than CIDP group. The combination of positive serum monoclonal protein and high TLI (if either one or both were present) discriminated POEMS from CIDP with a sensitivity of 94.1% and 47.1% and specificity of 76.5% and 100.0%, respectively.@*CONCLUSIONS@#POEMS syndrome could be distinguished from CIDP through typical clinical and electrophysiological characteristics in practice. The combination of serum monoclonal protein and high TLI might raise the sensitivity of detecting POEMS syndrome.

A retrospective analysis of first confirmed tubercular lymphadenitis in 129 cases / 中华传染病杂志

Objective@#To analyze and summarize the clinical characteristics of tubercular lymphadenitis, and to improve the ability of diagnosis. @*Methods@#Clinical records of 129 patients first confirmed with tubercular lymphadenitis were collected retrospectively from Nanfang Hospital of Southern Medical University between January 2012 and December 2016. The categorical variables were described with the percentage (%) and compared with the chi-squaue test. Non-normal distribution data were described with M(P25, P75) and compared with rank sum test.@*Results@#The disease courses were different in all cases, mostly of 1-3 months (45.7%). Among the cases, 83 cases (73.6%) complained of lymph node enlargement. The predominant involved lymph node site was cervical (56.6%) with main presentation of single lymph node (61.2%). Only a few cases presented with fever (34.1%). The positive rate of histological examinations was 94.3%, while the positive rate of T cell spot test of tuberculosis infection (T-SPOT.TB) test was 93.3% and purified protein derivative (PPD) test was 69.6%. In the diagnosis of tubercular lymphadenitis, 100 cases (77.5%) were confirmed by histological examinations, 27 cases (20.9%) were given diagnostic treatment, and only 2 case (1.6%) was confirmed by culture. The average period of diagnosis was (10.4±6.5) days. The median age of patients with fever was 50.5 years old with a median disease course of 2.5 months, while the median age of patients fever was 35(24, 49) years old with a median disease course of 1.2(0.5, 6.0) months. The differences between two groups were statistically significant (Z=-3.118 and -2.982, respectively, both P<0.05). Patients with fever had higher proportion of swollen deep lymph nodes (54.5% vs 11.8%), elevated white blood cell counts (34.1% vs 7.1%) and neutrophils (31.8% vs 1.8%), elevated erythrocyte sedimentation rate (97.1% vs 56.1%), elevated C-reactive protein (95.0% vs 40.0%) and received diagnostic treatment (47.7% vs 7.1%) than patients with no fever (χ2=27.337, 15.545, 13.567, 19.347, 25.410 and 28.974, respectively, all P<0.05). @*Conclusions@#Most patients of tubercular lymphadenitis do not present with typical symptoms which might lead to misdiagnose in early stage. The histological examinations and T-SPOT.TB test are especially essential, and histological examinations is the most important diagnostic method. Patients without symptoms of tuberculous poisoning are more common in young people, and the confirmation of diagnosis are mainly based on histological examinations. Patients with symptoms of tuberculous poisoning are more common in middle-aged, with longer duration and deep lymph node involved, which is more serious and nearly half of which are confirmed with diagnostic treatment.

Clinical study of preoperative enteral nutrition in elderly colorectal cancer patients with nutritional risk / 重庆医学

Objective To observed the influence of preoperative enteral nutrition(EN) on postoperative nutritional status,immune function and complications in elderly patients with colorectal cancer complicating nutritional risk.Methods The NRS2002 nutritional risk screening criteria was used to select 70 elderly patients with colorectal cancer complicating nutritional risk,including 36 cases in the EN group and 34 cases in the control group.The EN support was given in the ENN group on preoperative 3 d.The levels of plasma total protein,prealbumin,albumin,transferrin,total lymphocyte count,plasma D-lactate(D-LAC) and plasma diamine oxidase (DAO) were detected on postoperative 1,3,5 7 d.The intraoperative intestinal cleanliness and postoperative complications were observed.Results The levels of plasma total protein,prealbumin,albumin,transferrin and total lymphocyte count in the EN group were significantly higher than those in the control group and the levels of D-LAC and DAO,and the incidence rates of abdominal infection and wound infection were significantly lower than those in the control group,the differences were statistically significant(P＜0.05).There was no statistically significant differences in the incidence rates of intestinal cleanliness and anastomotic leakage between the two groups (P＞0.05).Conclusion Preoperative EN support therapy in the patients with colorectal cancer complicating nutritional risk can significantly improve clinical prognosis.

Identification of role of PI3K in mediating necroptosis of L929 cells induced by tumor necrosis factor alpha / 军事医学

Objective To identify the role of phosphatidylinositol-3-kinase(PI3K) in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) and the involved mechanism.Methods Knockdown of p110α,receptor-interacting protein 1(RIP1) or both p110αand RIP1 was mediated by the specific short hairpin RNA (shRNA) lentivirus and verified by RT-PCR or Western blotting .In addition , Western blotting was used to detect phosphorylation of mixed lineage kinase domain-like protein(MLKL) and protein kinase B(AKT) or tetramerization of MLKL.Cell death was measured by micros-copy and flow cytometry.Results AKT phosphorylation and TNFα-induced necroptosis of L929 cells were suppressed by the inhibitors of PI3K or AKT, as well as p110αknockdown.Moreover, RIP1 knockdown did not inhibit L929 cell death induced by TNFαplus Z-VAD, but the RIP1-independent necroptosis was inhibited by p 110αknockdown.In addition, p110αknockdown suppressed MLKL phosphorylation and tetramerization induced by TNFαwith Z-VAD in L929 cells. Conclusion PI3K mediates necroptosis of L929 cells induced by TNFαby activating AKT and MLKL, respectively.

UFLC-DAD-ESI-IT-TOFMSn Analysis on Biotransformation of Tongmai Formula Incubated with Human Intestinal Bacteria / 中草药·英文版

Objective To investigate the biotransformation of Tongmai formula (TMF) in incubated system of human intestinal flora (HIF). Methods The technique of ultra fast liquid chromatography with diode array detector and coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry (UFLC-DAD-ESI-IT-TOFMSn) was adopted to determine the products of TMF biotransformed by HIF. Results Totally 66 constituents were detected and identified according to the accurate mass measurements (< 5 ppm) and effective MSn fragment ions. Meanwhile, the potential biotransformational pathways of compounds in TMF transformed by HIF were firstly proposed. Desugarization, hydroxylation, and methylation were the major reactions in the biotransformation mechanism of TMF by HIF. Conclusion This study will be helpful to clarify the material basis of pharmacological activities from TMF in vivo.

STIM1 gene silencing suppresses tumor formation of human hypopharyngeal carcinoma cell line FaDu in nude mice / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the inhibition effect of STIM1 gene silencing on tumor growth of human hypopharyngeal carcinoma cell lines FaDu in nude mice.</p><p><b>METHODS</b>STIM1 gene in FaDu was silenced by lentiviral infection, and the effect of inhibition was detected by Real-time PCR and Western blot after lentiviral infection. Nude mice were divided into 2 groups, 5 mice in each group. Inhibition group: subcutaneous inject FaDu cells which STIM1 expression was inhibited.</p><p><b>CONTROL GROUP</b>subcutaneous inject FaDu cells infected with negative control siRNA-expressing lentivirus. Tumor volumes were measured by calipers, and small animal imaging was detected by NightOWL system on the day 10, 14, 18 and 22 after tumor inoculated. Tumor weights were evaluated in the day 22 after tumor inoculated. Statistical analysis was performed using standard student test(P value threshold was 0.05).</p><p><b>RESULTS</b>The expressions of human STIM1 gene and protein in FaDu cells were suppressed effectively after STIM1-siRNA lentiviral infection. The mean tumor volumes of control group and inhibition group were (51±25) mm3 and (40±35) mm3, respectively, on the day 10, (262±107) and (106±41) mm3 on the day 14, (716±226) and (340±158) mm3 on the day, (1 682±592) mm3 and (917±252)mm3 on the day 22 (P<0.05). On the day 22, the tumor weight was (1.22±0.41) g in control group and (0.66±0.26) g in STIM1-siRNA group (P<0.05). Small animal imaging showed that the tumors had a smaller fluorescence range with lower signal intensity in STIM1-siRNA group than in control group on the day 14, 18 and 22.</p><p><b>CONCLUSION</b>The expression of STIM1 in human hypopharyngeal carcinoma cell lines FaDu can be inhibited effectively by lentiviral infection, causing the inhibition of tumor formation and growth.</p>

Expression of STIM1 gene in human hypopharyngeal carcinoma cell line FaDu and its effect on FaDu cell apoptosis / 局解手术学杂志

Objective To study the expression of STIM 1 gene in human hypopharyngeal carcinoma cell line FaDu and its effect on FaDu cell apoptosis .Methods Lentivirus infection was used to knock STIM 1 down in FaDu cells .Group STIM1-siRNA: the expression of STIM1 in FaDu cell was inhibited by STIM 1-siRNA lentivirus .Group control:FaDu cells were infected by negative control siRNA lentivirus . Real-Time PCR was applied to identify the efficacy of lenticirus infection and the expression of STIM 1 in FaDu cells.Western blot was used to identify the expression of STIM 1 protein after lenticirus infection .Flow cytometry assay was performed to detect the apoptosis of FaDu cells in the two groups.The data were statistically analyzed with SPSS 17.0 software.Results Compared with GAPDH (Ct=12.08 ±0.05),the expression of STIM1 in FaDu cells was significant expressed (Ct=22.21 ±0.05,P<0.001).Real-Time PCR analysis the relative mRNA expression of STIM1 in FaDu cells of control group and STIM 1-siRNA group were (1.00 ±0.08) and (0.12 ±0.01) respectively (P<0.001). Western blot showed that the expression of STIM 1 gene and protein in FaDu cells were inhibited significantly after STIM 1-siRNA lentiviral in-fection,which was in accordance with the results of Real-Time PCR analysis.Flow cytometry assay showed that the siRNA-mRNA group had a higher apoptosis percentage (9.81 ±0.56)% compared to the control group (4.36 ±1.32)%,with statistically significant difference (P<0.05).Conclusion STIM1 gene correlated significantly with FaDu cell apoptosis .It inhibits apoptosis of FaDu cells ,and it may be a potential diagnostic and therapeutic target for the hypopharyngeal carcinoma .

Expression of YKL-40 and TLR4 in patients with chronic rhinosinusitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the expression of YKL-40, TLR4 and NF-κB in chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP and CRSsNP), and to investigate their expressional correlation and the potential role in pathogenesis of CRS.</p><p><b>METHODS</b>The specimens were obtained from sinus mucosa and inferior turbinate mucosa of the patients with informed consent. The different expression of YKL-40, TLR4 and NF-κB among each group was detected by real time RT-PCR and immunohistochemistry (S-P method). SPSS 17.0 software was used to analyze the data.</p><p><b>RESULTS</b>mRNA level: The relative expression of YKL-40 in CRSwNP group (0.91±0.17) was higher than those in the control group (0.49±0.09), the difference was significant (t=2.12, P<0.05). The relative expression of TLR4 in CRSsNP group (0.88±0.19) and CRSwNP group (0.67±0.13) were lower than those in control group (1.48±0.14), the differences were significant (t value was -4.11, -2.48, all P<0.05). The relative expression of NF-κB in CRSsNP group (0.69±0.13) and CRSwNP group (0.72±0.14) were lower than those in control group (1.20±0.15), the differences were significant (t value was 2.33, 2.27, all P<0.05). Protein level: The expression of YKL-40 in CRSwNP group was stronger than that in CRSsNP group and control group (U value was 72.5 and 73, all P<0.01). The expression of TLR4 in CRSwNP group and CRSsNP group was weaker than that in control group (U value was 62 and 38, all P<0.01). There was a negative correlation between YKL-40 and TLR4 (rmRNA=-0.741, P<0.01; rprotein=-0.46, P<0.05) in CRSwNP group.</p><p><b>CONCLUSIONS</b>The expression of YKL-40 in pantients with CRSwNP is higher than those in healthy control and CRSsNP patients. There was a negative correlation between YKL-40 and TLR4. Both of them may be involved in the pathogenesis of CRSwNP.</p>

Biotransformation by human intestinal flora and absorption-transportation characteristic in a model of Caco-2 cell monolayer of d-corydaline and tetrahydropalmatine / 中国中药杂志

<p><b>OBJECTIVE</b>To study the biotransformation by human intestinal flora, and the absorption and transportation characteristic in a model of human colon adenocarcinoma cell lines (Caco-2 cell) monolayer of d-corydaline (CDL) and tetrahydropalmatine (THP).</p><p><b>METHOD</b>CDL or THP was incubated with crude enzymes of human intestinal flora under the anaerobic environment and 37 degrees C conditions to transform CDL or THP. Caco-2 cell monolayer was used as an intestinal epithelial cell model for determination of the permeability of CDL or THP from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. Transportation parameters and permeability coefficients (P(app)) were then calculated, and P(app) values were compared with the reported values for model compounds, propranolol as a well absorbed drug and atenolol as a poor absorbed drug. The concentration of CDL or THP was measured by HPLC coupled with photodiode array detector.</p><p><b>RESULT</b>CDL or THP in the human intestinal flora incubation system did not happen biotransformation. In the Caco-2 cell monolayer model, the P(app) magnitudes of both CDL and THP were 1 x 10(-5) cm x s(-1) in the bi-directional transport, which were identical with propranolol. And their transports were concentration dependent between 0-180 min.</p><p><b>CONCLUSION</b>Both CDL and THP may be stable in the human intestinal flora incubation system, and their absorption and transportation in the human Caco-2 cell monolayer model are mainly via passive diffusion mechanism.</p>

Studies on biotransformation of chemical constituents of tongmai formula by human intestinal flora / 中国中药杂志

To study the chemical constituents in Tongmai formula (TMF) after biotransformation by human intestinal flora (HIF), water extract of TMF was anaerobically incubated with HIF at 37 degrees C. Column chromatographic methods over silica gel, Sephadex LH-20 and semi-preparative high-performance liquid chromatography as well as recrystallization were used to isolate and purify the chemical constituents in TMF after biotransformation by HIF. The chemical structures of isolated compounds were identified on the basis of MS and NMR data. Twenty-six compounds were obtained and identified as phenylpropionic acid (1), 6"-O-acetylpuerarin (2), formononetin(3), daidzein(4), p-hydroxyphenylpropionic acid (5), 3-indolepropionic acid (6), genistein (7), isoformononetin (8), isoononin (9), a mixture of (-)-puerol B-2"-O-glucopyranoside (10a) and (+) -puerol B-2"-O-glucopyranoside (10b), 8-hydroxydaidzein (11), puerol A (12), 3'-methoxy-6"-O-acetylpuerarin (13), 6"-O-acetyldaidzin (14), 3'-methoxydaidzin (15), puerol B (16), 3-methyluracil (17), genistin (18), daidzin (19), 3'-methoxypuerarin (20), mirificin (21), swertiamarin (22) , daidzein-7, 4'-O-glucoside (23), adenine (24), 3'-hydroxypuerarin (25), and puerarin (26). After biotransformation by HIF, the glycosides in TMF were transformed into aglycone and/or less glycosyl compounds along with some hydroxylation and demethylation reactions. Therefore, the glycosides in the TMF are the pro-drug.

Hippocampus quinolinic acid modulates glutamate and NMDAR/mGluR1 in chronic unpredictable mild stress-induced depression / 生理学报

The present study was to investigate the role of the quinolinic acid (QUIN) and its relationship with N-methyl-D-aspartic acid (NMDA) receptor and metabotropic glutamate receptor 1 (mGluR1) in depression induced by chronic unpredictable mild stress (CUMS) in hippocampus. CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal injections of QUIN, QUIN antagonist Ro61-8048, non-competitive NMDA receptor antagonist MK-801 and mGluR1 antagonist AIDA were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The concentration of glutamic acid (Glu) and the expression of its receptor subunits in hippocampus were detected by HPLC and Western blot, respectively. The QUIN content in hippocampus was determined by enzyme linked immunosorbent assay (ELISA). The result showed that CUMS significantly induced the depressive-like behaviors in rats, increased the contents of QUIN and Glu, and upregulated the expression of NMDA receptor subunits NR2B and mGluR1 in hippocampus. Microinjection of QUIN into hippocampus resulted in animal depressive-like behaviors, and increased the content of Glu and the expression of NR2B and mGluR1 significantly. QUIN antagonist Ro61-8048 effectively restrained the depression-like behaviors induced by CUMS, and decreased the content of Glu and the expression of NR2B and mGluR1 significantly. Intrahippocampal injections of MK-801 and AIDA effectively improved the depression-like behaviors induced by CUMS and decreased the Glu content. The results suggest that CUMS may contribute to the production and release of QUIN in hippocampal microglia. QUIN results in elevation of Glu level via NMDA receptor and mGluR1, and the increase of expression of NR2B and mGluR1 in hippocampus, which leads to depression-like behaviors in the end.

Studies on metabolism of total terpene ketones from Swertia mussotii with human intestinal bacteria / 中国中药杂志

<p><b>OBJECTIVE</b>To study the metabolism of total terpene ketones from Swertia mussotii with human intestinal bacteria.</p><p><b>METHOD</b>Total terpene ketones were incubated with human intestinal bacteria under an anaerobic environment and at 37 degrees C. The metabolites were extracted by ethyl acetate processing, detected by HPLC-DAD method. A qualitative analysis was made for its metabolites by HPLC-MS.</p><p><b>RESULT</b>Eight metabolites were detected from total terpene ketones from S. mussotii with human intestinal bacteria, and two of them were preliminarily identified as gentianine and mangiferin aglycon.</p><p><b>CONCLUSION</b>Total terpene ketones can be metabolized with human intestinal bacteria, which provides basis for experiments on the metabolism process total terpene ketones from S. mussotii with human intestinal bacteria.</p>

Development of HPLC Method to Evaluate Drug-processing Technique of Eucommiae Cortex / 中草药·英文版

Objective To establish a RP-HPLC method investigate the processing technique and mechanism of Eucommiae Cortex.Methods The RP-HPLC method was applied to simultaneously determining six ingredients,geniposidic acid,geniposide,genipin,chlorogenic acid,(+)-pinoresinol-di-β-D-glucopyranoside,and(+)-syringaresinol-di-β-D-glucopyranoside,in the different processed barks of Eucommia ulmoides.Results The valid method with good accuracy could be well used to study the processing technique of E.ulmoides;Besides,target ingredients in E.ulmoide were decreased within 6 h when they were processed.Conclusion Established RP-HPLC is a reliable method which could be used to research the processing technique of the barks ofE.ulmoides.Moreover,the result of this study could be provided with significant evidence of processed barks of E.ulmoides.

Repairing cartilage defects using chondrocyte and osteoblast composites developed using a bioreactor / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Articular cartilage injury is a common disease, and the incidence of articular wear, degeneration, trauma and sports injury is increasing, which often lead to disability and reduced quality of life. Unfortunately repair of articular cartilage defects do not always provide satisfactory outcomes.</p><p><b>METHODS</b>Chondrocyte and osteoblast composites were co-cultured using a bioreactor. The cartilage defects were treated with cell-β-tricalcium phosphate (β-TCP) composites implanted into osteochondral defects in dogs, in vivo, using mosaicplasty, by placing chondrocyte-β-TCP scaffold composites on top of the defect and osteoblast-β-TCP scaffold composites below the defect.</p><p><b>RESULTS</b>Electron microscopy revealed that the induced chondrocytes and osteoblast showed fine adhesive progression and proliferation in the β-TCP scaffold. The repaired tissues in the experimental group maintained their thickness to the full depth of the original defects, as compared with the negative control group (q = 12.3370, P < 0.01; q = 31.5393, P < 0.01).</p><p><b>CONCLUSIONS</b>Perfusion culture provided sustained nutrient supply and gas exchange into the center of the large scaffold. This perfusion bioreactor enables the chondrocytes and osteoblasts to survive and proliferate in a three-dimensional scaffold.</p>

Repair of cartilage defects using chondrocyte and osteoblast composites in vitro cultured in bioreactor / 中华创伤杂志

Objective To assess the feasibility of chondrocyte and osteoblast composites in vitro cultured in bioreactor in repairing cartilage defects.Methods Marrow mesenchymal stem cells were isolated and cultured in vitro,and then were induced to chondrocytes and osteoblasts by growth factor.Chondrocytes and osteoblasts were cocultured in bioreactor for 21 days to form the composites.The adhesion,extension and proliferation of chondrocytes and osteoblasts were observed under scanning electron microscope.The cartilage defects on canine model were repaired with the chondrocyte and osteoblast composites.Results The induced chondrocytes and osteoblasts had fine adhesion,extension and proliferation in the β-TCP scaffold.The repaired tissues in experimental group maintained their thickness to the full depth of the original tissues.A statistical difference was observed between negative control group and experimental group(q=12.337 0,P ＜ 0.01)and between blank control group and experimental group (q=31.539 3,P ＜0.01).Conclusion Perfusion bioreactor makes chondrocyte and osteoblast survive and proliferate in a three-dimensional scaffold and increases the composition rate of the chondrocyte and osteoblast.