Military Medical Research

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ISSN / EISSN : 2054-9369 / 2054-9369
Published by: Springer Nature (10.1186)
Total articles ≅ 374
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Yun-Juan Nie, Shuo-Hua Wu, Ying-Hua Xuan,
Published: 12 May 2022
Military Medical Research, Volume 9, pp 1-10; https://doi.org/10.1186/s40779-022-00382-3

Abstract:
Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.
Qian-Qian Yuan, Shu-Xuan Xiao, Omar Farouk, Yu-Tang Du, Fereshte Sheybani, Qing Ting Tan, Sami Akbulut, Kenan Cetin, Afsaneh Alikhassi, Rami Jalal Yaghan, et al.
Published: 26 April 2022
Military Medical Research, Volume 9, pp 1-15; https://doi.org/10.1186/s40779-022-00380-5

Abstract:
Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.
Xian Lin, Feng Wang, Jian Chen, Jing Liu, Yi-Bin Lin, Li Li, Chuan-Ben Chen, Qin Xu
Published: 14 April 2022
Military Medical Research, Volume 9, pp 1-16; https://doi.org/10.1186/s40779-022-00378-z

Abstract:
Background: Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. In the current study, we determined the relevant players and role of N6-methyladenine (m6A) RNA methylation in cervical cancer progression. Methods: The roles of m6A RNA methylation and centromere protein K (CENPK) in cervical cancer were analyzed using bioinformatics analysis. Methylated RNA immunoprecipitation was adopted to detect m6A modification of CENPK mRNA. Human cervical cancer clinical samples, cell lines, and xenografts were used for analyzing gene expression and function. Immunofluorescence staining and the tumorsphere formation, clonogenic, MTT, and EdU assays were performed to determine cell stemness, chemoresistance, migration, invasion, and proliferation in HeLa and SiHa cells, respectively. Western blot analysis, co-immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter, cycloheximide chase, and cell fractionation assays were performed to elucidate the underlying mechanism. Results: Bioinformatics analysis of public cancer datasets revealed firm links between m6A modification patterns and cervical cancer prognosis, especially through ZC3H13-mediated m6A modification of CENPK mRNA. CENPK expression was elevated in cervical cancer, associated with cancer recurrence, and independently predicts poor patient prognosis [hazard ratio = 1.413, 95% confidence interval = 1.078 − 1.853, P = 0.012]. Silencing of CENPK prolonged the overall survival time of cervical cancer-bearing mice and improved the response of cervical cancer tumors to chemotherapy in vivo (P < 0.001). We also showed that CENPK was directly bound to SOX6 and disrupted the interactions of CENPK with β-catenin, which promoted β-catenin expression and nuclear translocation, facilitated p53 ubiquitination, and led to activation of Wnt/β-catenin signaling, but suppression of the p53 pathway. This dysregulation ultimately enhanced the tumorigenic pathways required for cell stemness, DNA damage repair pathways necessary for cisplatin/carboplatin resistance, epithelial-mesenchymal transition involved in metastasis, and DNA replication that drove tumor cell proliferation. Conclusions: CENPK was shown to have an oncogenic role in cervical cancer and can thus serve as a prognostic indicator and novel target for cervical cancer treatment.
Yan Wang, Hong-Qian Lv, Xuan Chao, Wen-Xin Xu, Yun Liu, Gui-Xia Ling,
Published: 12 April 2022
Military Medical Research, Volume 9, pp 1-15; https://doi.org/10.1186/s40779-022-00376-1

Abstract:
Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, which can give rise to the loss of motor and sensory function. Due to its complex pathological mechanism, the treatment of this disease still faces a huge challenge. Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord. Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI. In this review, hydrogel-based multimodal therapeutic strategies to repair SCI are provided, and a combination of hydrogel scaffolds and other therapeutic modalities are discussed, with particular emphasis on the repair mechanism of SCI.
Wei Wang, Yu-Jie Yang, Ri-Hong Zhang, Jing-Yu Deng, Zhe Sun, Sharvesh Raj Seeruttun, Zhen-Ning Wang, Hui-Mian Xu, , Zhi-Wei Zhou
Published: 7 April 2022
Military Medical Research, Volume 9, pp 1-11; https://doi.org/10.1186/s40779-022-00375-2

Abstract:
Background: Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with < 16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both < 16 (Limited set) and ≥ 16 (Adequate set) rLNs. Methods: All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N’) resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. Results: Significant difference in OS between the Limited and Adequate set (corresponding N0–N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N’ classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N’0 = N0adequate + pT1N0M0limited, N’1 = N1adequate + N0limited (excluding pT1N0M0limited), N’2 = N2adequate + N1limited, N’3a = N3aadequate + N2limited, and N’3b = N3badequate + N3alimited). This N’ classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN’M system over the 8th AJCC edition and was successfully validated using the SEER dataset. Conclusion: The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with < 16 and ≥ 16 rLNs.
Xian-Tao Zeng, Ying-Hui Jin, Tong-Zu Liu, Fang-Ming Chen, De-Gang Ding, Meng Fu, Xin-Quan Gu, Bang-Min Han, Xing Huang, Zhi Hou, et al.
Published: 1 April 2022
Military Medical Research, Volume 9, pp 1-19; https://doi.org/10.1186/s40779-022-00371-6

Abstract:
Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.
Shuai-Fei Ji, Lai-Xian Zhou, Zhi-Feng Sun, Jiang-Bing Xiang, Shao-Yuan Cui, Yan Li, Hua-Ting Chen, Yi-Qiong Liu, Huan-Huan Gao, , et al.
Published: 29 March 2022
Military Medical Research, Volume 9, pp 1-13; https://doi.org/10.1186/s40779-022-00372-5

Abstract:
Background: Large skin defects severely disrupt the overall skin structure and can irreversibly damage sweat glands (SG), thus impairing the skin’s physiological function. This study aims to develop a stepwise reprogramming strategy to convert fibroblasts into SG lineages, which may provide a promising method to obtain desirable cell types for the functional repair and regeneration of damaged skin. Methods: The expression of the SG markers cytokeratin 5 (CK5), cytokeratin 10 (CK10), cytokeratin 18 (CK18), carcino-embryonic antigen (CEA), aquaporin 5 (AQP5) and α-smooth muscle actin (α-SMA) was assessed with quantitative PCR (qPCR), immunofluorescence and flow cytometry. Calcium activity analysis was conducted to test the function of induced SG-like cells (iSGCs). Mouse xenograft models were also used to evaluate the in vivo regeneration of iSGCs. BALB/c nude mice were randomly divided into a normal group, SGM treatment group and iSGC transplantation group. Immunocytochemical analyses and starch-iodine sweat tests were used to confirm the in vivo regeneration of iSGCs. Results: EDA overexpression drove HDF conversion into iSGCs in SG culture medium (SGM). qPCR indicated significantly increased mRNA levels of the SG markers CK5, CK18 and CEA in iSGCs, and flow cytometry data demonstrated (4.18 ± 0.04)% of iSGCs were CK5 positive and (4.36 ± 0.25)% of iSGCs were CK18 positive. The addition of chemical cocktails greatly accelerated the SG fate program. qPCR results revealed significantly increased mRNA expression of CK5, CK18 and CEA in iSGCs, as well as activation of the duct marker CK10 and luminal functional marker AQP5. Flow cytometry indicated, after the treatment of chemical cocktails, (23.05 ± 2.49)% of iSGCs expressed CK5+ and (55.79 ± 3.18)% of iSGCs expressed CK18+, respectively. Calcium activity analysis indicated that the reactivity of iSGCs to acetylcholine was close to that of primary SG cells [(60.79 ± 7.71)% vs. (70.59 ± 0.34)%, ns]. In vivo transplantation experiments showed approximately (5.2 ± 1.1)% of the mice were sweat test positive, and the histological analysis results indicated that regenerated SG structures were present in iSGCs-treated mice. Conclusion: We developed a SG reprogramming strategy to generate functional iSGCs from HDFs by using the single factor EDA in combination with SGM and small molecules. The generation of iSGCs has important implications for future in situ skin regeneration with SG restoration.
Lu-Yao Li, Jie Han, Lan Wu, Cheng Fang, Wei-Guang Li, Jia-Min Gu, Tong Deng, Chang-Jiang Qin, Jia-Yan Nie,
Published: 28 March 2022
Military Medical Research, Volume 9, pp 1-16; https://doi.org/10.1186/s40779-022-00373-4

Abstract:
Background: Studies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia (BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics. Methods: We analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry (LC–MS/MS). Results: High-throughput sequencing results showed that gut microbiota beta-diversity increased (P < 0.01) in the BPH group vs. control group. Muribaculaceae (P < 0.01), Turicibacteraceae (P < 0.05), Turicibacter (P < 0.01) and Coprococcus (P < 0.01) were significantly decreased in the BPH group, whereas that of Mollicutes (P < 0.05) and Prevotella (P < 0.05) were significantly increased compared with the control group. Despite profound interindividual variability, the levels of several predominant genera were different. In addition, there were no statistically significant differences in several bacteria. BPH group vs. control group: Firmicutes (52.30% vs. 57.29%, P > 0.05), Bacteroidetes (46.54% vs. 41.64%, P > 0.05), Clostridia (50.89% vs. 54.66%, P > 0.05), Ruminococcaceae (25.67% vs. 20.56%, P > 0.05). LC–MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis (R = 0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae, Bifidobacteriaceae and differential metabolites. Conclusion: Our findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.
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