Effects of higher femoral tunnels on clinical outcomes, MRI, and second-look findings in double-bundle anterior cruciate ligament reconstruction with a minimal 5-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR.@*METHODS@#From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up.@*RESULTS@#Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 ( P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization ( P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference ( P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 ( P = 0.027).@*CONCLUSION@#The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.

Effect of LncRNA p21 regulating Hippo-YAP signaling pathway on formation of abdominal aortic aneurysm in mice and its mechanism / 中国药理学通报

Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE

Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection / 中国血吸虫病防治杂志

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

Meta-analysis of the role of fibular fixation in tibiofibular fractures / 中国骨伤

OBJECTIVE@#To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.@*METHODS@#The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups.@*RESULTS@#A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison.@*CONCLUSION@#Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

Immunoprotective effect of recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice / 中国血吸虫病防治杂志

Objective To evaluate the immunoprotective effect of active immunization with recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice. Methods Female BALB/c mice at 6 weeks of age, each weighing approximately 20 g, were divided into the recombinant protein immunization group, the infection control group and the normal control group, of 25, 18, 15 mice in each group, respectively. Mice in the recombinant protein immunization group were given active immunization with recombinant BmPPIase protein, and 18 mice with the highest antibody titers were intraperitoneally injected with 100 μL of B. microti-infected whole blood 2 weeks after the last immunization. Mice in the infection control group were intraperitoneally injected with 100 μL of B. microti-infected whole blood, while 15 mice in the normal control group received no treatment. Blood samples were collected from mice in the recombinant protein immunization group and the infection control group on days 0 to 30 post-immunization for detection of B. microti infection, and blood samples were collected on days 0, 7, 14, 21, and 28 post-immunization for routine blood tests with a blood cell analyzer and for detection of serum cytokines using cytometric bead array. Results Anti-BmPPIase antibodies were detected in 25 mice in the recombinant protein immunization group 2 weeks after the last immunization, with titers of 5 × 103 to 8 × 104. B. microti infection rate peaked in mice in both the recombinant protein immunization and the infection control group on day 7 post-immunization, with positive infection rates of 13.3% and 50.0%, and there were significant differences between the two groups in terms of B. microti infection rate on days 3 (χ2= 113.18, P < 0.01), 5 (χ2 = 475.22, P < 0.01), 7 (χ2 = 465.98, P < 0.01) and 9 post-infection (χ2= 18.71, P < 0.01), while the B. microti infection rate tended to be 0 in both groups on day 11 post-immunization. Routine blood tests showed higher red blood cell counts [(5.30 ± 0.50) × 1012 to (9.87 ± 0.24) × 1012 counts/L)] and hemoglobin levels [(89.67 ± 22.80) to (148.60 ± 3.05) g/L)] in the recombinant protein immunization group than in the infection control group on days 0 to 28 post-immunization. Cytometric bead array detected higher serum interferon-γ [(748.59 ± 17.56) to (3 858.28 ± 1 049.10) fg/mL], tumor necrosis factor-α [(6 687.34 ± 1 016.64) to (12 708.13 ± 1 629.79) fg/mL], interleukin (IL)-6 [(611.05 ± 75.60) to (6 852.68 ± 1 554.00) fg/mL] and IL-17a [(167.68 ± 185.00) to (10 849.27 ± 355.40) fg/mL] and lower IL-10 levels [(247.65 ± 138.00) to (18 787.20 ± 2 830.22) fg/mL] in the recombinant protein immunization group than in the infection control group during the study period. Conclusions Recombinant BmPPIase protein induces up-regulation of interferon-γ, tumor necrosis factor-α and presents a high immunoprotective activity against B. microti infection in mice, which is a potential vaccine candidate protein.

Progress on the mechanism and treatment of Parkinson's disease-related pathological pain / 生理学报

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms, including bradykinesia, resting tremor, and progressive rigidity. More recently, non-motor symptoms of PD, such as pain, depression and anxiety, and autonomic dysfunction, have attracted increasing attention from scientists and clinicians. As one of non-motor symptoms, pain has high prevalence and early onset feature. Because the mechanism of PD-related pathological pain is unclear, the clinical therapy for treating PD-related pathological pain is very limited, with a focus on relieving the symptoms. This paper reviewed the clinical features, pathogenesis, and therapeutic strategies of PD-related pathological pain and discussed the mechanism of the chronicity of PD-related pathological pain, hoping to provide useful data for the study of drugs and clinical intervention for PD-related pathological pain.

A preliminary survey of female breast characteristics based on three-dimensional images of breast cone-beam computed tomography / 中国辐射卫生

Objective To establish a method to characterize the size and density of the female breast based on three-dimensional images of breast cone-beam computed tomography (CBCT), and describe the breast characteristics of women in a region of China, and to explore its value in dosimetric assessment for breast CBCT examinees. Methods We retrospectively surveyed the breast CBCT images of 203 women in a grade A tertiary hospital in a southwestern city of China from January 2021 to March 2023. The effective diameter of the breast at the chest-wall (Deff), chest wall-to-nipple length (CNL), the effective diameter of the breast at half of CNL (Dh/2), breast volume (BV), glandular volume (GV), and volumetric breast density (VBD) were measured using the specific tools of the Koning Imaging Viewer system. The differences between groups were assessed using the Kruskal-Wallis H test. The correlation between variables was assessed using the Spearman’s correlation coefficient. Results The median values of Deff, Dh/2, CNL, BV, GV, and VBD of the surveyed population were 11.9 cm, 8.3 cm, 6.5 cm, 327.7 cm3, 47.0 cm3, and 15.4%, respectively. GV and VBD had significant negative correlations with age. Deff, Dh/2, CNL, and BV were significantly negatively correlated with VBD. Conclusion We established a quantitative method to analyze female breast characteristics based on three-dimensional breast CBCT images, and preliminarily characterized the female breast in a region of China, which can provide methodological support for the investigation of female breast characteristics in various regions of China in the future.

Analysis on the Key Points of Clinical Research Management Based on the Scientific Research Big Data Platform of a Tertiary Hospital / 中国医学伦理学

With the rapid development of healthcare big data and artificial intelligence technology, how to utilize the massive medical data generated based on clinical diagnosis and treatment has become an important issue to be solved in the field of clinical research. Clinical diagnosis and treatment data is an essential part of healthcare big data, and also the main field of healthcare big data research. With the continuous deepening and extensive development of informatization, hospitals have accumulated a large number of patient-centered clinical diagnosis and treatment data. Deeply mining and analyzing these data through big data technology can provide reference for precise diagnosis and treatment, and standardized prevention and control of diseases. However, conducting relevant research still faces many difficulties and blockages, such as the increased risk of data leakage or abuse, and the difficulty in implementing informed consent. To safely, legally and efficiently utilize clinical diagnosis and treatment data to conduct clinical research and fully tap into the value of these precious medical resources, a tertiary hospital in Beijing has built a research big data platform and developed relevant systems to effectively solve the problems of blockages and difficulties in the application of rich clinical resources to clinical research, and improve the service quality of medical institutions and the conversion rate of scientific research achievements. By introducing the key points and management methods in the implementation of clinical research based on the scientific research big data platform, analyzing and exploring the existing problems and improvement measures, this paper aimed to provide theoretical basis and system reference for high-quality and efficient health and medical big data clinical research, inspire and promote the continuous improvement of medical research management, and promote the development of medical and health science and technology innovation.

Randomized Controlled Trial of Anti-reflux Mucosectomy Versus Radiofrequency Energy Delivery for Proton Pump Inhibitor-refractory Gastroesophageal Reflux Disease

Background/Aims@#The efficacy and safety of anti-reflux mucosectomy (ARMS) or radiofrequency energy delivery in the treatment of gastroesophageal reflux disease (GERD) have been reported, but the difference between the 2 remains unclear. @*Methods@#This was a single center, randomized, comparative clinical study. Patients with symptoms of heartburn and/or regurgitation despite proton pump inhibitor treatment were randomly assigned to either ARMS group (n = 20) or radiofrequency group (n = 20).Primary outcome was the standardized GERD questionnaire (GERDQ) at 2 years after the procedures. Secondary outcomes were the proportions of patients with complete proton pump inhibitor (PPI) cessation and patients satisfied with the treatment. @*Results@#A total of 18 patients randomized to ARMS and 16 to radiofrequency were analyzed in this study. The operation success rate of the 2 groups was 100%. In both ARMS and radiofrequency groups, GERDQ scores at 2 years after the procedures were significantly lower than that before operation (P = 0.044 and P = 0.046). At 2 years postoperatively, the scores of GERDQ did not differ between the 2 groups (P = 0.755). There was no significant difference in the rate of discontinuation of PPIs and patient satisfaction in the ARMS and radiofrequency groups (P = 0.642 and P = 0.934). @*Conclusions@#The clinical efficacy of ARMS and radiofrequency for the PPI-refractory GERD is equivalent. ARMS, the efficacy of which could be maintained for at least 2 years, is promising endoscopic management for the treatment of refractory GERD.

Progress of Research on Role of Eosinophils in Irritable Bowel Syndrome / 胃肠病学

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by repeated abdominal pain and changes in defecation habits, which seriously affects the quality of life of patients. The occurrence and development of IBS are affected by many factors. As an inherent component of the gastrointestinal tract, eosinophils play a role in maintaining the local homeostasis of intestine. The activation of intestinal eosinophils plays a direct or indirect role in the occurrence and development of IBS. This article reviewed the progress of research on the potential role of eosinophils in IBS.

CeO / 中国生物化学与分子生物学报

Drought is a common limiting factor affecting rice yield and quality. Cerium oxide nanoparticles(nanoceria) have been widely reported to improve crop stress tolerance. However, the effects and mechanisms of nanoceria on rice drought tolerance are still unknown. The aim of this study is to investigate whether nanoceria can improve rice drought tolerance by modulating reactive oxygen species(ROS) homeostasis and nitric oxide(NO) levels. Our results showed that compared with no-nanoparticle treatment, nanoceria significantly increased the fresh weight of rice seedlings under drought stress(19%, P < 0. 05). Also, under drought stress, the ROS level of rice leaves treated with nanoceria was significantly lower(82%, P < 0. 05) than leaves treated with buffer. The leaf NO level after nanoceria treatment, however, is significantly higher(46%, P < 0. 05) than that with no-nanoparticle treatment under drought stress. Moreover, compared with control plants, nanoceria maintained better membrane integrity in rice leaf cells under drought stress, showing a 70% decrease(P < 0. 05) in dead leaf cells. This study explores the mechanisms underlying nanoceria’s improved rice drought tolerance by affecting ROS and NO levels, which not only further enriches our knowledge about the interaction between nanoparticles and crops under abiotic stress but also gives more support on the sustainable development of nano-enabled agriculture.

Expression change and role of myeloma cancer gene mRNA, microRNA-540-3p, circular RNA-04996 in the liver inflammatory reaction during the rat liver regeneration / 解剖学报

Objective To explore the role pathway and pattern of the transcription factor myeloma cancer gene (MYC) and its mRNA interaction with microRNA(miRNA, miR) and ciccular RNA(circRNAs) at 0 hour and 6 hour in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy，PH) model was prepared as described by Higgins, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNAs(ceRNA) of remnant liver were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at 0 hour and 6 hours after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-540-3p displays 3.00±0.43 and 0.79±0.01, circRNA_04996 showed 1.43±0.43 and 3.14±0.94. At the same time, the four kinds of inflammatory reaction-related genes plasminogen activator urokinase receptor (PLAUR), tumor necrosis factor (TNF), interleukin 1 receptor type 2 (IL1R2), ect, which were prometed in expression by MYC, were down-regulated at 0 hour after PH, but the inflammatory reaction-related genes natriuretic peptide A (NPPA), nuclear receptor subfamily O group B member 2 (NROB2) and peroxisome proliferator activated receptor alpha (PPARA), which were inhibited in expression by MYC, were up-regulated at 0 hour after PH. On the other hand, the three kinds of inflammatory reaction-related genes PLAUR, TNF, IL1R2, ect, which are prometed in expression by MYC, were up-regulated at 6 hours after PH, but the inflammatory reaction-related genes NPPA, NROB2 and PPARA, which were inhibited in expression by MYC, were down-regulated at 6 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the inflammatory reaction-related genes, which are regulated by MYC, and are helpful for the hepatocyte to be in non-inflammatory reaction state at 0 hour after PH and to be in inflammatory reaction state at 6 hours after PH.

Expression change and role of sex determining region box transcription factor 2 mRNA and the non-coding RNA in the hepatocyte stem changes during the rat liver regeneration / 解剖学报

Objective To explore the role pathway and pattern of the sex determining region box transcription factor 2 (SOX2) and its mRNA interaction with microRNA(miRNAs, miR) and circular RNA(circRNA) at 0 hour and 2 hours in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNAs(ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and 2 hours after PH, the ratio value of SOX2 mRNA shows 1.00±0.09 and 2.15±0.48, miR-3558-3p displays 4.53± 0.10 and 0.81±0.16, circRNA_18404 shows 1.24±0.04 and 11.10±0.57, circRNA_18045 displays 1.97±0.47 and 4.44± 0.23. At the same time, the eight kinds of cell dedifferentiation-related genes AT-rich interaction domain 5A (ARID5A), activating transcription factor 3 (ATF3), BTG anti-proliferation factor 2 (BTG2), etc, which are prometed in expression by SOX2, were down-regulated at 0 h after PH, but the cell differentiation-related genes interferon regulatory factor 6 (IRF6) and somatostatin (SST), which are inhibited in expression by SOX2, were up-regulated at 0 hour after PH. On the other hand, the eight kinds of cell dedifferentiation-related genes ARID5A, ATF3, BTG2, etc, which are promoted in expression by SOX2, were up-regulated at 2 hours after PH, but the cell differentiation-related gene SST, which is inhibited in expression by SOX2, was down-regulated, and IRF6 had no meaningful changes in expression at 2 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNA, SOX2, its mRNA is inhibited by miRNA, and the cell stem-related genes, which are regulated by SOX2, are helpful for the hepatocyte to be in differentiation state at 0 hour after PH and to be in stem state at 2 hours after PH.

Expression change and role of Kruppel-like factor 4 mRNA, microRNA-881-3p, circular RNA_20298 and circular RNA_14826 in the hepatocyte apoptosis during the rat liver regeneration / 解剖学报

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.

Expression change and role of myeloma cancer gene mRNA and the non-coding RNA in the hepatocyte cycle initiation and termination during the rat liver regeneration / 解剖学报

Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.

Non-muscle myosin heavy chain 9 gene-related disorders with thrombocytopenia: report of two pedigrees and literature review / 中华儿科杂志

Objective: To summarize the clinical characteristics and gene variants of 2 pedigrees of non-muscle myosin heavy chain 9 related diseases (MYH9-RD) in children. Methods: The basic information, clinical features, gene variants and laboratory tests of MYH9-RD patients from 2 pedigrees confirmed in the First Affiliated Hospital of Zhengzhou University in November 2021 and July 2022 were analyzed retrospectively. "Non-muscle myosin heavy chain 9 related disease" "MYH9" and "children" were used as key words to search at Pubmed database, CNKI and Wanfang database up to February 2023. The MYH9-RD gene variant spectrum and clinical data were analyzed and summarized. Results: Proband 1 (male, 11 years old) sought medical attention due to epistaxis, the eldest sister and second sister of proband 1 only showed excessive menstrual bleeding, the skin and mucous membrane of the their mother were prone to ecchymosis after bumping, the uncle of proband 1 had kidney damage, and the maternal grandmother and maternal great-grandmother of proband 1 had a history of cataracts. There were 7 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that the proband 1 MYH9 gene had c.279C>G (p.N93K) missense variant, and family verification analysis showed that the variant was inherited from the mother. A total of 4 patients including proband 1 and family members were diagnosed with MYH9-RD. The proband 2 (female, 1 year old) sought medical attention duo to fever and cough, and the father's physical examination revealed thrombocytopenia. There were 2 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that there was a c.4270G>A (p.D1424N) missense variant in the proband 2 MYH9 gene, and family verification analysis showed that the variant was inherited from the father. A total of 2 patients including proband 2 and his father were diagnosed with MYH9-RD. A total of 99 articles were retrieved, including 32 domestic literatures and 67 foreign literatures. The MYH9-RD cases totaled 149 pedigrees and 197 sporadic patients, including 2 pedigrees in our study. There were 101 cases with complete clinical data, including 62 sporadic cases and 39 pedigrees. There were 56 males and 45 females, with an average age of 6.9 years old. The main clinical manifestations were thrombocytopenia, skin ecchymosis, and epistaxis. Most patients didn't receive special treatment after diagnosis. Six English literatures related to MYH9-RD caused by c.279C>G mutation in MYH9 gene were retrieved. Italy reported the highest number of cases (3 cases). Twelve literatures related to MYH9-RD caused by c.4270G>A mutation in MYH9 gene were retrieved. China reported the highest number of cases (9 cases). Conclusions: The clinical manifestations of patients in the MYH9-RD pedigrees varied greatly. MYH9 gene c.279C>G and c.4270G>A mutations are the cause of MYH9-RD.

Report content and prenatal diagnosis of non-invasive prenatal testing for sex chromosome aneuploidy / 中华妇产科杂志

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.

Effect of clonal hematopoiesis in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia after chemotherapy / 中华血液学杂志

Objective: To investigate the effect of clonal hematopoiesis (CH) in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia (AML) after chemotherapy. Methods: Retrospective analysis was performed on 86 patients with NPM1(mut) AML newly diagnosed and treated in the First Affiliated Hospital of Soochow University between July 2016 and June 2019. Their clinical data and NGS test results at diagnosis were analyzed. Moreover, bone marrow samples in remission were tested using Sanger sequencing. The log-rank test was used to analyze the difference in hematopoietic recovery, and Cox proportional hazard models were used to analyze the prognostic factors affecting hematopoietic recovery. Results: The median age of the 86 NPM1(mut) AML patients was 50 years (15-69 years). There were 39 males and 47 females. Forty-one patients were induced with intensity chemotherapy ("7 + 3"), whereas 45 patients were treated with low-dose cytarabine-based induction chemotherapy. At diagnosis, The most common mutations in the patients were FLT3, DNMT3A, TET2, and IDH1/IDH2 mutations. CH-associated mutations persisted in 21 patients during remission, and the mutations were DNMT3A, TET2, ASXL1, and IDH1/IDH2. The recovery time of neutrophils in patients with CH-associated mutations in remission was consistent with that in patients without CH in remission (P=0.282) but the recovery time of platelets in patients with CH in remission was significantly longer[26 (95% CI 21-32) days vs 25 (95% CI 23-26) days, P=0.032]. Furthermore, univariate analysis indicated that age, induced chemotherapy program, and CH in remission were risk factors for platelet recovery, whereas multivariate analysis indicated that induced chemotherapy program and CH in remission were independent risk factors for platelet recovery (HR=0.454, P=0.001 and HR=0.520, P=0.027, respectively) . Conclusion: CH in remission delays the hematopoietic recovery of patients with NPM1(mut) AML after chemotherapy.

Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway / 中西医结合学报

OBJECTIVE@#This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats.@*METHODS@#The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA.@*RESULTS@#APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05).@*CONCLUSION@#EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.