[Research progress of tunneling nanotube in bone biology].

Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.

[Short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease].

Objective: To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety. Results: A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m2 (HR=5.04, 95%CI: 1.50-16.91, P=0.009) and biological remission at 6 weeks of treatment (HR=15.22, 95%CI: 3.16-73.38, P=0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%). Conclusions: More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.

[Reoperation rate and related factors in patients with Crohn's disease].

Objective: To analyze the cumulative reoperation rate of postoperative Crohn's disease (CD) patients and investigate the operation reasons and the effects of drugs on surgical recurrence. Method: Patients with Crohn's disease who had undergone intestinal resection from January 2000 to March 2020 in Peking Union Medical College Hospital were enrolled. Patients were divided into reoperation and non-reoperation group according to whether they had a second operation. And the basic characteristics and the reasons for the primary and second operation were retrospectively analyzed. Meanwhile, patients were divided into low-risk reoperation group and high-risk group based on risk stratification. Kaplan-Meier methods were performed to analyze the cumulative surgical recurrence rate and to compare the recurrence rate in different risk stratification and chi-square tests was used to analyze the effects of different maintenance drugs on reoperation. Result: A total of 160 patients were enrolled in the study. There were 110 males and 50 females, and the age at first operation was (35.6±14.1) years old. There were 40 patients in the reoperation group and 120 patients in the non-reoperation group. According to univariate analysis, the proportion of male gender(P=0.030), penetrating phenotype(P<0.001), history of appendectomy before the primary surgery(P=0.035) and no postoperative maintenance therapy (P<0.001) were higher in surgical recurrence group. In terms of the operation reasons, intestinal obstruction accounted for the highest proportion in the primary operation (26.9%, 43/160), while the intestinal fistula was the most common reason for reoperation (42.5%, 17/40). After the primary surgery, the cumulative reoperation rates at 1, 3, 5 and 10 years were 5.9% (9 cases), 12.3% (17 cases), 21.8% (25 cases) and 37.6% (34 cases), respectively. The ten years cumulative reoperation rate of the high-risk group was 42.8% (31 cases), which was much higher than that of low-risk group (19.8%, 3 cases), and the difference was statistically significant (P=0.006). There was no statistically significant difference in the surgical recurrence rate of low-risk group patients(P=0.076)whether maintenance therapies were added or not, while the recurrence rate of high-risk group patients who did not receive maintenance therapy was higher than those who received immunosuppressant with or without (±) 5-aminosalicylic acid (ASA) (P=0.001) and biological agent±5-ASA (P=0.001), and the difference was statistically significant. Conclusion: Patients with CD are still at risk of reoperation after surgery. Immunosuppressive agents and biologics can prevent patients from reoperation in high-risk groups.

[Relationship between matrix Gla protein and clinical features of ulcerative colitis].

Objective: To analyze the relationship between matrix Gla protein(MGP) and clinical characteristics of patients with ulcerative colitis (UC). Methods: Fifty-one UC patients who were admitted to the gastroenterology department of Peking union medical college hospital from July 1, 2015 to May 31, 2017 were included. Twenty-seven healthy subjects in the same period were included as normal controls. The expression of MGP mRNA in the colonic mucosa was detected by real-time fluorescence quantitative PCR. Clinical data of the patients were collected during a 2-year follow-up. The public data set containing MGP gene expression profile of UC patients was downloaded from the GEO database, and was divided into four groups according to the microscopic Mayo score. The differential expression of MGP in each group was analyzed. Results: All the fifty-one UC patients were followed up. The expression of MGP mRNA in the colonic mucosa of UC patients treated with hormone and immunosuppressive agents or biological agents or surgery was higher than that of patients treated with mesalazine. MGP mRNA expression was positively correlated with C-reactive protein level. It was also higher in the colonic mucosa of UC patients with clostridium difficilis or cytomegalovirus infection than that of patients without opportunistic infection. The difference of MGP mRNA expression between groups in GEO public data set was statistically significant(P<0.01), showing an up-regulation trend with the aggravation of inflammation. The expression level of MGP was moderately correlated with the microscopic Mayo score. The relationship between MGP mRNA expression and lifestyle, lesion range, erythrocyte sedimentation rate, parenteral manifestations and recurrence frequency of UC patients was not obvious. Conclusions: MGP is associated with colonic inflammation and its abnormal expression can help to predict the disease activity of patients with UC.

[Clinical characteristics of metastasis-induced acute pancreatitis in patients with lung cancer].

Objective: To analyze the clinical features and prognosis of lung cancer patients with metastasis-induced acute pancreatitis (MIAP), and to provide clues for early diagnosis. Methods: The characteristics and prognosis of 8 patients with MIAP in lung cancer admitted to Peking Union Medical College Hospital from January 2002 to September 2019 were retrospectively analyzed and were compared with non-tumor-induced AP. Results: Sevencases(7/8) were Mild AP, one (1/8) was Severe AP. Four patients (4/8) presented with AP as the reporting sign and lung cancer was not diagnosed until (112±36) days after the onset of AP. Clinical manifestations included abdominal pain (8/8), weight loss (4/8), nausea and vomiting (2/8), and jaundice (1/8). Stages of lung cancer were all Ⅳ.Histopathology proved that seven cases (7/8) were small cell lung cancer, and one case (1/8) was poorly differentiated adenocarcinoma. The median survival time was 11 months. Compared with non-tumor-induced AP, lung cancer patients with MIAP were older[(62±9) vs (48±15), P=0.018], the incidence of primary pancreatic duct dilatation (37.5% vs 3.1%, P=0.004) and abdominal lymphadenopathy (37.5% vs 6.3%, P=0.017) were higher; the level of hemoglobin [105.3±15.6) g/L vs (147.9±24.8) g/L, P<0.001] and hematocrit [(31.4±5.3) vs (42.5±6.1), P<0.001] were lower. Conclusions: Patientswith MIAP in lung cancer had poor outcome and unspecific symptoms. Old age, anemia, main pancreatic duct dilatation and abdominal lymphadenopathy are diagnostic clues that merit clinical attention.

[Analysis on clinical features of patients with ulcerative colitis associated colorectal cancer].

Objective: To analyze the clinical features of ulcerative colitis associated colorectal cancer (UC-CRC). Methods: A total of 869 inpatients with Ulcerative Colitis (UC) in Peking Union Medical Hospital from January 1998 to January 2018 were continuously enrolled. Clinical data and the outcome of colorectal cancer (CRC) were collected via medical records and telephone follow-up. Chi-square test and logistic regression model were used to analyze the data. Results: There were 16 patients in 869 UC inpatients who were diagnosed with CRC during a period of 7 548 person years and the incidence rate of UC-CRC was 1.84%. Compared to UC inpatients without CRC, a longer course of disease (OR=1.087, 95% CI:1.046-1.129) , a lower usage rate of 5-Aminosalicylic Acid(5-ASA) (OR=0.218, 95% CI:0.052-0.915) and a higher incidence rate of intestinal stenosis (OR=16.533, 95% CI:3.824-71.478) were found in UC inpatients with CRC. Conclusions: A long disease course is a risk factor for UC patients developing CRC, while 5-ASA therapy can reduce the risk of suffering from CRC. For UC patients with intestinal stenosis, CRC should be warned for occurring.

A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations.

BACKGROUND: A phase III trial was conducted to compare the safety and efficacy of erlotinib with that of gefitinib in advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations in exon 19 or 21. METHODS: Eligible patients were randomised to receive erlotinib (150 mg per day) or gefitinib (250 mg per day) orally until disease progression or unacceptable toxicity. We aimed to determine whether erlotinib is superior to gefitinib in efficacy. The primary end point was progression-free survival. RESULTS: A total of 256 patients were randomised to receive erlotinib (N=128) or gefitinib (N=128). Median progression-free survival was not better with erlotinib than with gefitinib (13.0 vs 10.4 months, 95% confidence interval (CI) 0.62-1.05, P=0.108). The corresponding response rates and median overall survival were 56.3% vs 52.3% (P=0.530) and 22.9 vs 20.1 months (95% CI 0.63-1.13, P=0.250), respectively. There were no significant differences in grade 3/4 toxicities between the two arms (P=0.172). CONCLUSIONS: The primary end point was not met. Erlotinib was not significantly superior to gefitinib in terms of efficacy in advanced non-small cell lung cancer with epidermal growth factor receptor mutations in exon 19 or 21, and the two treatments had similar toxicities.

Association of Klotho and interleukin 6 gene polymorphisms with aging in Han Chinese population.

Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (-174G/C) and rs1800796 (-572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn't correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.

Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling.

CONTEXT: One approach to protect against liver fibrosis is the use of herb-derived natural compounds, such as hydroxysafflor yellow A (HSYA). The antifibrosis effect of HYSA against liver fibrosis has been investigated; however, its mechanisms have not yet been entirely revealed. OBJECTIVES: To study the protective effects of HSYA on liver fibrosis induced by carbon tetrachloride (CCl4) and a high-fat diet (HFD), and to determine the mechanism of action of HSYA. MATERIALS AND METHODS: CCl4 and HFD were used to mimic liver fibrosis in rats, and serum biochemical indicators were determined. The antifibrosis effects of HSYA were evaluated and its mechanisms were investigated by histopathological analysis, immunohistochemical staining, enzyme-linked immunosorbent assays, real-time-PCR, and western blotting. RESULTS: HSYA reduced CCl4- and HFD-mediated liver fibrosis and ameliorated serum biochemical indicator, downregulated the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) (0.31 ± 0.03 protein, 0.59 ± 0.02 mRNA) and transformin growth factor-ß1 (TGF-ß1) (0.81 ± 0.02 protein, 0.58 ± 0.04 mRNA), and upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) (1.57 ± 0.13 protein, 2.48 ± 0.19 mRNA) and matrix metallopeptidases-2 (MMP-2) (2.31 ± 0.16 protein, 2.79 ± 0.22 mRNA) (p < 0.01, versus model group). These effects were significantly attenuated by PPAR-γ antagonist GW9662 via blocking the phosphorylation of p38 MAPK. DISCUSSION AND CONCLUSION: These data demonstrate a novel role for HSYA in inhibiting CCl4- and HFD-mediated liver fibrosis, and reveal that PPAR-γ and p38 MAPK signaling play pivotal roles in the prevention of liver fibrosis induced by CCl4 and HFD.

Construction of an integral formula of biological age for a healthy Chinese population using principle component analysis.

BACKGROUND: Whereas chronological age (CA) cannot distinguish functional differences among individuals of the same age, the biological age (BA) may be used to reflect the functional state of the body. The purpose of this study was to construct an integral formula of the BA, by using principle component analysis (PCA). METHODS: The vital organ function of 505 healthy individuals of Han origin (age 35-91 years) was examined. A total of 114 indicators of cardiovascular, pulmonary, and brain functions, and clinical, inflammatory, genetic, psychological, and life habit factors were assessed as candidate indicators of aging. Candidate indicators were submitted with CA to correlation and redundancy analyses. The PCA method was used to build an integral formula of the BA for the population. RESULTS: Seven biomarkers were selected in accordance with a certain load standard. These biomarkers included the trail making test (TMT), pulse pressure (PP), mitral valve annulus ventricular septum of the peak velocity of early filling (MVES), minimum carotid artery intimal-medial thickness (IMTmin), maximum internal diameter of the carotid artery (Dmax), maximal midexpiratory flow rate 75/25 (MMEF75/25), and Cystatin C (CysC). The formula for the BA was: BA = 0.0685 (TMT) + 0.267 (PP) - 1.375 (MVES) + 22.443 (IMTmin) + 2.962 (Dmax) - 2.332 (MMEF75/25) + 16.104 (CysC) + 0.137 (CA) + 0.492. CONCLUSION: Several genetic and lifestyle indicators were considered as candidate markers of aging. However, ultimately, only markers reflecting the function of the vital organs were included in the BA formula. This study represents a useful attempt to employ multiple indicators to build a comprehensive BA evaluation formula of aging populations.

Activation of PPARγ is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress.

Oxidative stress caused hepatic fibrosis by activating hepatic stellate cells (HSCs), which were implemented by depressing PPARγ activation. Hydroxysafflor yellow A (HSYA) as a nature active ingredient with antioxidant capacity was able to effectively attenuate oxidative stress mediated injury. So it will be very interesting to study effect of HSYA on HSCs activation and liver fibrosis, and reveal the role of PPARγ·CCl4 and H2O2 were used to mimic oxidative stress mediated hepatic injury in vitro and in vivo respectively. The anti-fibrosis effects of HSYA were evaluated and its mechanisms were disclosed by applying western blot, histopathological analysis, flow cytometry, RT-PCR and ELISA. Our results showed that HSCs activation and proliferation could be induced by oxidative stress, and the expressive levels of TGF-ß1 and TIMP-1, the serum levels of ALT, AST, HA, LN, III-C and IV-C were also enhanced by oxidative stress, which is correlated with liver fibrosis (p<0.05 or p<0.01). HSYA was able to effectively inhibit oxidative stress mediated hepatic injury by increasing the activities of antioxidant enzymes, up regulating the expression of PPARγ and MMP-2, and down regulating the expression of TGF-ß1 and TIMP-1, and reducing α-SMA level. The protective effect of HSYA can be significantly attenuated by GW9662 via blocking PPARγ (p<0.05 or p<0.01). Taken together, these results demonstrate that HSYA is able to significantly protect the liver from oxidative stress, which requires for HSYA to stimulate PPARγ activity, reduce cell proliferation and suppress ECM synthesis.

Effects of interval between fusion and activation, cytochalasin B treatment, and number of transferred embryos, on cloning efficiency in goats.

To improve the efficiency of somatic cell nuclear transfer (SCNT) in goats, we evaluated the effects of the interval between fusion and activation (1 to 5 h), cytochalasin B (CB) treatment after electrofusion, and the number of transferred embryos on the in vivo and in vitro development of cloned caprine embryos. The majority of the reconstructed embryos had condensed chromosomes and metaphase-like chromosomes at 2 and 3 h after fusion; cleavage and blastocyst rates from those two groups were higher (P < 0.05) than those of embryos activated 1, 4, or 5 h after fusion. Treatment with CB between fusion and activation improved in vitro and in vivo development of nuclear transfer (NT) goat embryos by reducing the fragmentation rate (P < 0.05). Although there were no significant differences in NT efficiency, pregnancy rate and kids born per recipient were increased by transfer of 20 or 30 embryos per recipient compared with 10 embryos. We concluded that CB treatment for 2 to 3 h between fusion and activation was an efficient method for generating cloned goats by somatic cell NT. In addition, increasing the number of embryos transferred to each recipient resulted in more live offspring from fewer recipients.

[Inhibiting gene expression in vivo by virus-mediated small interfering RNA].

Inhibiting gene expression in specific tissues and organs through intravenous injection would be the ultimately preferred method of disease therapy. Here, we report the successful delivery of lentivirus-mediated small interfering RNA (siRNA) to suppress the GFP gene expression in living mice. First, a lentiviral vector with siRNA (len-siRNA) driven by H1 promoter was constructed to suppress GFP expression effectively in Mel cells. When the len-siRNA virus was injected into transgenic mice, the GFP expression was significantly suppressed (over 15% reduction) in the recipient mice compared to the control mice and the suppressing effect lasted more than one week after injection. Our results demonstrate a new effective approach to inhibit gene expression by siRNA and lentiviral vectors. Further development of this suppression of gene expression siRNA drug should result in applications not only for cancers but also for infectious and immune diseases.

[Clinical and pathological features of type I and III membranoproliferative glomerulonephritis].

Analysis and comparisons were made between the clinical and pathological data obtained from 42 cases of type I and 17 cases of type III membranoproliferative glomerulonephritis (MPGN). It was shown that type I MPGN differed from type III remarkably in following respects: (1) Nephrosis was a salient feature of type III while hypertension, impairment of renal function and hematuria were more common in type I. (2) Pathological glomerular sclerosis, tubular interstitial changes and crescents formation occurred frequently in type I but not in type III. (3) Long term prognosis for type III was much better than type I. It is concluded the type III MPGN is a distinct clinical entity which differs from the classical type I MPGN in many aspects.

Primary glomerulonephritis in China. Analysis of 1001 cases.

The morphologic classification and clinical spectrum of 1,001 cases of primary glomerulonephritis (GN) in Jinling Hospital during 1980-1988 were analysed. It was found that the incidence of mesangial type lesion including mesangial proliferative GN, IgA nephropathy and IgM nephropathy ranks first (21.5%, 32.1% and 10.1% respectively), which is not only the commonest cause of patients clinically manifesting nephrotic syndrome and gross hematuria but also the predominant type of nephritis causing uremia and hypertension.