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Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies

Stem Cell Res Ther. 2021 Aug 18;12(1):461. doi: 10.1186/s13287-021-02496-2.

ABSTRACT

BACKGROUND: Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF.

METHODS: We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software.

RESULTS: A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI -2.58 to -1.51, P < 0.001, I2 = 90%).

CONCLUSIONS: MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.

PMID:34407861 | DOI:10.1186/s13287-021-02496-2

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Effect of primary lesion resection on the prognosis of patients with advanced breast cancer

Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):878-882. doi: 10.3760/cma.j.cn112152-20200429-00392.

ABSTRACT

Objective: To explore the effect of the resection of the primary lesion on the prognosis for patients with stage Ⅳ breast cancer. Methods: A total of 132 breast cancer patients who were first diagnosed as stage Ⅳ in the Hebei Cancer Hospital from June 2008 to June 2015 were divided into two groups: the primary resection group (n=85) and the unresection group (n=47). The influences of primary resection, timing of operation, lymph node removal or dissection and radiotherapy on the prognosis of stage Ⅳ breast cancer patients were analyzed. Results: Multivariate Logistic regression analysis showed that visceral metastasis was an independent influencing factor for primary lesion resection in stage Ⅳ breast cancer patients (OR=2.590, 95% CI: 1.090-6.159). Multivariate Cox regression analysis showed that primary resection was an independent factor for the improvement of prognosis in stage Ⅳ breast cancer patients (OR=0.582, 95% CI: 0.400-0.847). The median overall survival (OS) was 37.20 months in the resection group, which was higher than 24.10 months in the unresection group (χ(2)=8.108, P=0.004). Among patients aged ≥50 years old, the median OS was 39.30 months in the resection group and 23.03 months in the unresection group, and the difference was statistically significant (χ(2)=14.191, P<0.001). The median OS was 38.00 months in the 66 patients with the operation time from diagnosis to resection of primary lesion<6 months (n=66), and 35.20 months for ≥6 months (n=19) (χ(2)=4.430, P=0.035), the difference was statistically significant (χ(2)=4.430, P=0.035). The median OR of axillary lymph node dissection and axillary lymph node excision group were 45.37 months and 33.44 months, respectively, the difference was statistically significant (χ(2)=7.832, P=0.005). The median OS of postoperative radiotherapy group and non-radiotherapy group were 44.80 months and 33.20 months, respectively, the difference was not statistically significant (χ(2)=2.950, P=0.086). Conclusion: Resection of the primary lesion may prolong the survival time of some advanced breast cancer patients.

PMID:34407595 | DOI:10.3760/cma.j.cn112152-20200429-00392

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Relationship between serum folate and CIN1 prognosis and its interaction with HR-HPV infection

Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):866-871. doi: 10.3760/cma.j.cn112152-20200812-00732.

ABSTRACT

Objective: To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection. Methods: From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection. Results: Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant (Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group (P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning (OR=0.422, 95%CI: 0.238-0.750), frequency of changing underwear (OR=0.574, 95%CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95%CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95%CI: 4.024-17.445), HR-HPV infection (OR=1.852, 95%CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95%CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95%CI: 0.279-0.824), synergy index was 2.632 (95%CI: 1.239-5.588), aOR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95%CI: 4.878-16.807). Conclusion: Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.

PMID:34407593 | DOI:10.3760/cma.j.cn112152-20200812-00732

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The value of synthetic MRI in differential diagnosis of benign and malignant breast lesions

Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):872-877. doi: 10.3760/cma.j.cn112152-20210322-00254.

ABSTRACT

Objective: To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions. Methods: From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter. Results: Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10(-3)mm(2)/s) was significantly higher than that of the malignant group (median 1.00×10(-3)mm(2)/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant (P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions: Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.

PMID:34407594 | DOI:10.3760/cma.j.cn112152-20210322-00254

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Increased expression of SEMA5B in gastric adenocarcinoma predicts poor prognosis: a study based on TCGA data

Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):856-860. doi: 10.3760/cma.j.cn112152-20200104-00005.

ABSTRACT

Objective: To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods: In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results: The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant (P<0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months (P=0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage (P<0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio(HR) of 1.042 (95%CI: 1.021-1.064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95%CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways (P=0.008), MAPK signaling pathways (P=0.047) and Notch signaling pathways (P=0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions: SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC.

PMID:34407591 | DOI:10.3760/cma.j.cn112152-20200104-00005

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Analysis of risk factors for delayed bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm

Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):861-865. doi: 10.3760/cma.j.cn112152-20210118-00057.

ABSTRACT

Objective: To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions. Methods: The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding. Results: A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group (P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm (OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion (OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions: The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.

PMID:34407592 | DOI:10.3760/cma.j.cn112152-20210118-00057

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Impact and clinical value of the revised 2019 Chinese HER-2 testing guidelines on the detect result evaluation of invasive breast cancer cases with equivocal HER-2 immunostaining by using fluorescence in situ hybridization

Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):833-837. doi: 10.3760/cma.j.cn112152-20200309-00183.

ABSTRACT

Objective: To investigate the impact and clinical significance of the revised 2019 Chinese HER-2 testing guidelines on the detecting result evaluation of invasive breast cancers with equivocal HER-2 immunostaining by using fluorescence in situ hybridization (FISH). Methods: A total of 569 cases of invasive breast cancers with HER-2 (+ + ) immunostaining evaluated according to the immunohistochemistry (IHC) guidelines of 2014 edition and 2019 edition from May to November 2019 were collected and further detected by FISH. The results of HER-2/CEPl7 double probe were respectively interpreted according to both the 2014 and 2019 Chinese HER-2 testing guidelines and the results were compared. Results: According to the 2014 guidelines, the number of HER-2 positive, equivocal and negative cases were 139 (24.43%), 67 (11.78%), and 363 (63.80%), respectively. Whereas according to the 2019 guidelines, 115 cases (20.21%) were the first group, 9 cases (1.58%) were the second group, 15 cases (2.64%) were the third group, 67 cases (11.78%) were the fourth group, and 363 cases were (63.80%) the fifth group, of which 130 cases (22.85%) were positive and 439 cases (77.15%) were negative by FISH detecting. Compared with the guideline of 2014 edition, the HER-2 positive rate of FISH detection reduced from 24.43% (139/569) to 22.85% (130/559) according to the application of the guideline of 2019 edition, but the difference was not statistically significant (P=0.567), while the negative rate increased from 63.80% (363/569) to 77.15% (439/569), with a statistically significant difference (P<0.05). Forty-three cases with incomplete weak to medium intensity of IHC membrane staining which were HER-2 (+ + ) according to 2014 guideline were changed to IHC (+ ) on the basis of the 2019 guideline. According to the FISH guideline of 2014 edition, 1 case (2.33%) was positive, 6 cases (13.95%) was equivocal and 36 cases (83.72%) was negative, while according to the 2019 FISH guideline, all of the 43 cases were negative. Conclusions: According to the guideline of 2019 edition, a proportion of cases changes from HER-2 (+ + ) to (+ ), and the HER-2 positive rate of FISH test decreases slightly, the negative rate increases, the equivocal result is eliminated, which provides a definite reference for screening patients who will be benefited from the targeted treatment of HER-2.

PMID:34407587 | DOI:10.3760/cma.j.cn112152-20200309-00183

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Analysis of factors affecting live birth outcome of frozen-thawed embryo transfer cycle

Zhonghua Yi Xue Za Zhi. 2021 Aug 24;101(32):2552-2558. doi: 10.3760/cma.j.cn112137-20210318-00684.

ABSTRACT

Objective: To analyze the related factors affecting the success of frozen-thawed embryo transfer (FET). Methods: A total of 563 couples treated in the Reproductive Medicine Center of Guangdong Hospital of Traditional Chinese Medicine from January 2017 to March 2020 were selected as subjects. A total of 736 FET cycles were included to analyze the live birth outcomes of FET. Pregnancy outcomes, pregnancy complications and embryo status of patients between the live birth group and the non-live birth group were compared. A multivariate logistic regression model was used to evaluate the association between the 15 candidate factors and live birth outcomes for identifying independent factors associated with the live birth outcomes of the FET. Results: Among the enrolled subjects, the men were (33±5) years old at sperm extraction while the women were (31±4) years old at ovum pick-up (OPU) and (32±4) years old at embryo transfer (ET) and their infertility duration were (3.5±2.6) years. There were 333 (45.2%) live birth cycles and 403 (54.8%) non-live birth cycles in the 736 FET cycles. Pregnancy complications occurred in 49 cases (14.7%) of the live birth group. The age of the women at ET ((31±4) vs (32±4) years), the age of the women at OPU ((30±4) vs (32±4) years) and the age of the men at sperm extraction ((33±4) vs (34±5) years) in the live birth group were all lower than those in the non-live birth group. The infertility duration was shorter ((3.2±2.2) vs (3.6±2.8) years), and the proportion of primary infertility was higher ((63.1%, 210 cases) vs (49.6%, 200 cases)) in the live birth group (P<0.05) than those in the non-live birth group. Multivariate logistic regression analyses showed that the age of woman at ET (OR (95%CI): 0.50 (0.27-0.92), P=0.026), the types of infertility (0.62 (0.43-0.88), P=0.008), the numbers of optimal embryos transferred (1.60(1.11-2.31), P=0.012), and the types of embryos transferred (2.43 (1.46-4.01), P=0.001) were statistically significant related factors for live birth outcome of FET. Conclusion: The age of the woman at ET, the types of infertility, the numbers of optimal embryos transferred and the types of embryos transferred are associated factors for the outcomes of live birth after FET.

PMID:34407582 | DOI:10.3760/cma.j.cn112137-20210318-00684

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Association between meibomian gland dysfunction and body mass index in Chinese adults

Zhonghua Yi Xue Za Zhi. 2021 Aug 24;101(32):2514-2518. doi: 10.3760/cma.j.cn112137-20210223-00466.

ABSTRACT

Objective: To evaluate the association of meibomian gland dysfunction (MGD) and body mass index (BMI) in Chinese adults. Methods: A total of 2 419 patients were retrospectively recruited between May and October 2013 from 33 ocular surface disease clinic in China. There were 780 males (32.2%) and 1 639 females (67.8%), aged 18-89 (46±16) years. BMI value of each patient was respectively calculated, and the patients were divided into underweight, normal weight, overweight and obesity groups accordingly. Meibomian gland-related examinations were performed in right eyes. Results: The number of the patients in four groups were 196, 1 556, 567 and 100, respectively. Compared with normal weight group, the rates of moderate to severe MGD (59.1%, 71.0% vs 49.9%) in overweight group and obesity group were higher, and the differences were statistically significant (both P<0.05). The scores of change in eyelid margin, meibomian gland dropout and meibum expressibility were significantly higher in overweight group and obesity group, compared with normal weight group (all P<0.05). Additionally, after stratified by age, all the above-mentioned three scores of obese patients were significantly higher than those of non-obese patients in young adult group. Multivariate logistic regression analysis showed that moderate to severe MGD was correlated with overweight (OR=2.19, 95%CI: 1.06-4.50, P=0.033) and obesity (OR=3.70, 95%CI: 2.57-5.04, P=0.008). Conclusion: Moderate to severe MGD significantly correlates with high BMI in Chinese adults.

PMID:34407576 | DOI:10.3760/cma.j.cn112137-20210223-00466

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Functional axillary dissection based on lymphatic drainage for breast cancer: a single center randomized clinical trial

Zhonghua Yi Xue Za Zhi. 2021 Aug 24;101(32):2531-2536. doi: 10.3760/cma.j.cn112137-20201210-03324.

ABSTRACT

Objective: To evaluate the effectiveness and safety of functional axillary dissection based on lymphatic drainage (FUND) in decreasing breast cancer-related lymphedema (BCRL) events. Methods: A total of 168 eligible patients in Zhongnan Hospital of Wuhan University from July 2018 to February 2019 were randomly assigned to the FUND group or axillary lymph node dissection (ALND) group using random number table generated by SPSS. In the FUND group, methylene blue (MB) was adopted to reveal the sentinel lymph node (SLN) for all patients; 0.1 ml MB was injected into the SLNs before resection to reveal the efferent lymphatic channels and subsequent-echelon lymph node. The blue-stained lymphatic channels were mapped by bluntly dissecting along the lymphatic drainage channels from the breast to the axilla. Then, the SLNs were removed and pathologically analyzed by immediate frozen sectioning (FS); if the SLNs were positive, the blue-stained bALNs in breast lymphatic level (BLL) Ⅱ were removed and sent for immediate FS; if the blue-stained ALNs in BLL Ⅱ were confirmed negative, the tissues in BLL Ⅱ were removed’en bloc’. Clinicopathologic information for all the patients in the two groups were collected. The fixed-point circumference volume measurement method and the Norman questionnaire scoring method were used to evaluate the arm lymphedema between the two groups. Clinicopathological characteristics, incidences of arm lymphedema, locoregional recurrence, and distant metastasis between the two groups were compared. Results: The mean age were (50.3±8.0) in the FUND group and (51.1±9.0) in the ALND group. Seventy-four cases (88.1%) in the FUND group successfully underwent FUND surgery, and patients whose breast lymphatics failed to be stained blue underwent standard ALND. There was no statistically significant difference in terms of age, BMI, histological types, surgical approaches and adjunct therapy between the FUND group (n=74) and ALND group (n=84) (P>0.05). The average operation time of the FUND group and the stand ALND group were (169±15) and (123±12) min respectively (range: 145-198, 103-146 min) (P<0.001), and the number of lymph nodes removed [M (Q1, Q3)] were 8.3 (6, 15) and 12.9 (7, 18) (P=0.019). The cumulative BCRL rate, within a median follow-up of 24 months and 23 months respectively for FUND and ALND group, were 10.8% (8/74) vs 23.8% (20/84) (P=0.033) measured by fixed-point circumference volume measurement method, and was 12.2% (9/74) vs 27.4% (23/84) by Norman questionnaire (P=0.018). There were no local regional recurrence events during the follow-up period between the two groups. Conclusion: For breast cancer patients with clinically node-positive axilla or positive SLN, FUND based on lymphatic drainage was a less radical axillary surgery, with which eliminating the risk of BCRL might be achieved.

PMID:34407579 | DOI:10.3760/cma.j.cn112137-20201210-03324