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Deep shale gas reservoirs have geological characteristics of high temperature, high pressure, high stress, and inferior ability to pass through fluids. The multi-stage fractured horizontal well is the key to exploiting the deep shale gas reservoir. However, during the production process, the effectiveness of the hydraulic fracture network decreases with the closure of fractures, which accelerates the decline of shale gas production. In this paper, we addressed the problems of unclear fracture closure mechanisms and low accuracy of shale gas production prediction during deep shale gas production. Then we established the fluidesolideheat coupled model coupling the deformation and fluid flow among the fracture surface, proppant and the shale matrix. When the fluidesolideheat coupled model was applied to the fracture network, it was well solved by our numerical method named discontinuous discrete fracture method. Compared with the conventional discrete fracture method, the discontinuous discrete fracture method can describe the three-dimensional morphology of the fracture while considering the effect of the change of fracture surface permeation coefficient on the coupled fractureematrix flow and describing the displacement discontinuity across the fracture. Numerical simulations revealed that the degree of fracture closure increases as the production time proceeds, and the degree of closure of the secondary fractures is higher than that of the primary fractures. Shale creep and proppant embedment both increase the degree of fracture closure. The reduction in fracture surface permeability due to proppant embedment reduces the rate of fluid transfer between matrix and fracture, which has often been overlooked in the past. However, it significantly impacts shale gas production, with calculations showing a 24.7% cumulative three-year yield reduction. This study is helpful to understand the mechanism of hydraulic fracture closure. Therefore, it provides the theoretical guidance for maintaining the long-term effectiveness of hydraulic fractures. [ABSTRACT FROM AUTHOR]

In light of carbon-neutral pledge, the oil and gas industry has been facing several critical new challenges in China. The current status and new challenges in terms of market mechanism reform, supply-consumption balance and key technology innovation in China's oil and gas industry are reviewed in the present study, and new strategies and roadmaps are proposed to cope with the challenges. The study found that (i) the oil and gas market faces challenges such as incomplete pricing mechanisms, unclear subject rights, and the lack of recognition and trading of carbon assets. (ii) the trade-off between short-term supply security and long-term low-carbon supply is the most critical issue. (iii) in addition to typical challenges such as immature technology and lack of funding support, the unclear multiple technology coupling development mode also poses problems for the low-carbon transformation of the oil and gas industry. To address these new challenges, comprehensive strategies and roadmaps for China's oil and gas industry towards carbon neutrality are proposed and discussed in the aspects of participating in market transactions, restructuring production and consumption, deploying key technology innovations, and planning enterprise strategies. The present study is expected to provide a blueprint for the future development of China's oil and gas industry towards carbon neutrality. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence andmetastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution. Methods: An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable. Furthermore, this material showed to promote bone healing, and could be conveniently prepared into porous scaffold by freeze-drying the solution. By means of introducing melatonin (MT) into the porous surfaces, the MT loaded PP5 scaffold with desirable sustained release ability was successfully prepared. The effectiveness of the MT loaded PP5 scaffold in promoting bone repair and antitumor properties was evaluated through both in vivo and in vitro experiments. Results and Discussion: The MT loaded PP5 scaffold is able to achieve the desired outcome of bone tissue repair and anti-bone tumor properties. Furthermore, our study demonstrates that the PP5 scaffold was able to enhance the anti-tumor effect of melatonin by improving cellular autophagy, which provided a therapeutic strategy for the comprehensive postoperative treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Objective: Local invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC. Methods: We used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion. Results: We demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells' proliferation, migration, and invasion. Conclusions: We revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. Objective: The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Methods: Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Results: Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm², 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm², 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Conclusion: Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a common metabolic disease that is associated with gut microbiota dysbiosis and iron metabolism. Salidroside (SAL) is the main ingredient of the traditional Chinese herb Rhodiola, previous studies have shown that SAL could reshape the gut microbiota and limit iron accumulation. Therefore, it is possible that SAL can act as an alternative therapy for diabetes, and its underlying mechanism is worth exploring. Methods: SAL was used to treat diabetic db/db mice. Serumglucose and iron levels and the histopathology of myocardial fibres were evaluated. The gut microbiota composition was determined by 16S rRNA Illumina sequencing technology. Results: Treatment with SAL significantly reduced blood glucose and ameliorated diabetic cardiomyopathy in diabetic db/db mice, which was accompanied by inhibited ferroptosis and iron accumulation. Furthermore, the 16S rRNA sequencing results showed that SAL induced a change in the gut microbiota composition. Overall, SAL could increase the proportion of probiotic bacteria and decrease Lactobacillus to improve gut microbiota. Specifically, SAL increased the ratio of Bacteroidetes to Firmicutes in diabetic mice. The most significant biomarker was the genus Lactobacillus between the MD group and the SAL group. In addition, COG and KEGG analyses suggested that SAL mainly participated in nutrient metabolism, among them iron metabolism was associated with the abundance of Lactobacillus. Conclusions: SAL could reduce the glucose level and protect against diabetic cardiomyopathy in diabetic mice, which might be mediated by the change in the gut microbiota and the regulation of iron metabolism. The findings suggested that SAL was a promising complementary option for diabetes therapy. [ABSTRACT FROM AUTHOR]

Objective: Matrix metalloproteinases (MMPs) are essential for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. MMPs have been widely studied in acute brain diseases. However, the relationship with Parkinson’s disease (PD) remains unclear. The purpose of this study was to evaluate the serum MMP3 and MMP9 levels of PD patients and analyze their correlation with non-motor symptoms. Methods: In this cross-sectional study, we recruited 73 patients with idiopathic PD and 64 healthy volunteers. Serum MMP3 and MMP9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with PD were assessed for non-motor symptoms using the Non-motor Symptoms Scale (NMSS) and Parkinson’s disease sleep scale (PDSS) and Mini Mental State Examination (MMSE). Results: Serum MMP3 levels were significantly decreased in PD patients, predominantly those with early-stage PD, compared with controls [12.56 (9.30, 17.44) vs. 15.37 (11.33, 24.41) ng/ml; P = 0.004], and the serum MMP9 levels of PD patients were significantly higher than those of healthy controls [522 (419, 729) vs. 329 (229, 473) ng/ml; P < 0.001]. MMP3 levels were positively correlated with the NMSS total score (r = 0.271, P = 0.020) and the single-item scores for item six, assessing the gastrointestinal tract (r = 0.333, P = 0.004), and there was an inverse correlation between serum MMP3 levels and PDSS score (r = –0.246, P = 0.036); meanwhile, MMP9 levels were positively correlated with the NMSS total score (r = 0.234, P = 0.047), and higher serum MMP9 levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [658 (504, 877) vs. 502 (397, 608) ng/ml, P = 0.008]. Conclusion: The serum MMP3 level of PD patients (especially early-stage patients) was significantly lower than that of the healthy control group, and the MMP9 level was significantly higher than that of the healthy control group. MMP3 and MMP9 levels correlate with sleep disturbance and cognitive function in PD patients, respectively. [ABSTRACT FROM AUTHOR]

Background: The "postural instability/gait difficulty" (PIGD) and "tremor-dominant" (TD) motor subtypes of Parkinson's disease (PD) differ in their clinical manifestations. The neurological basis of these differences is unclear. Methods: We performed voxel-based morphometric analysis and measured amplitudes of low-frequency fluctuation (ALFF) on 87 PIGD patients and 51 TD patients. We complemented this neuroanatomical comparison with seed-to-voxel analysis to explore differences in functional connectivity. Results: The PIGD group showed significantly smaller gray matter volume in the medial frontal gyrus (mainly on the right side) than the TD group. Across all patients, gray matter volume in the medial frontal gyrus correlated negatively with severity of PIGD symptoms after controlling for age (r = -0.250, p = 0.003), but this correlation was not observed in separate analyses of only PIGD or TD patients. The PIGD group showed greater functional connectivity of the right superior frontal gyrus with the left lingual gyrus, right lateral occipital cortex, and right lingual gyrus. ALFF did not differ significantly between the two groups. Conclusion: Postural instability/gait difficulty may be associated with smaller gray matter volume in medial frontal gyrus than TD, as well as with greater functional connectivity between the right superior frontal gyrus and occipital cortex. These results may help explain the clinical differences between the two motor subtypes of PD. [ABSTRACT FROM AUTHOR]

Background. Although the procedure requires a small surgical incision and a short duration, incision infection rate is very low in thyroidectomy; however, doctors still have misgivings about infection events. Aim. We retrospectively analyzed the prevention of incision infection without perioperative use of antibacterial medications following thyroidectomy. Materials and Methods. 1166 patients of thyroidectomy were not administered perioperative antibiotics. Unilateral total lobectomy or partial thyroidectomy was performed in 68.0% patients with single-side nodular goiter or thyroid adenoma. Bilateral partial thyroidectomy was performed in 25.5% patients with nodular goiter or Graves'' disease. The mean time of operation was 80.6 ± 4.87 (range: 25-390) min. Results. Resuturingwas performed in two patients of secondary hemorrhage from residual thyroid following bilateral partial thyroidectomy. Temporally recurrent nerve paralysis was reported following right-side total lobectomy and left-side subtotal lobectomy in a nodular goiter patient. One case had suppurative infection in neck incision 5 days after bilateral partial thyroidectomy. Conclusions. Thyroidectomy, which is a clean incision, involves a small incision, short duration, and minor hemorrhage. If the operation is performed under strict conditions of sterility and hemostasis, antibacterial medications may not be required to prevent incision infection, which reduces cost and discourages the excessive use of antibiotics. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 16-year-old girl who experienced for two months a solitary and firm nodule on the right upper arm. It states that dermatologic examination identified a nodule with one centimeter in size, while the histopathologic examination showed the fibrous capsule surrounding the tumor nests. The article discusses pilomatricoma as a benign cutaneous tumor having bullous appearance and usually occurs on the shoulder and upper arm areas of females.

Background: Activating transcription factor 2 (ATF2) and signal transducer and activator of transcription 3 (STAT3) play important roles in the pathogenesis of various tumors, but ATF2 expression/activation and the relationship with STAT3 activation have not yet been investigated in extramammary Paget’s disease (EMPD). Objective: To investigate potential contributions of ATF2 and STAT3 pathways to the pathogenesis of EMPD. Method: Paraffin-embedded 45 EMPD specimens (43 primary EMPD and 2 nodal metastases) were subjected to immunohistochemical staining for ATF2, phosphorylated (p)-ATF2 and p-STAT3. Results: P-ATF2 expression in advanced EMPD, non-invasive EMPD and normal skin (NS) controls were 97.9 ± 1.8%, 82.0 ± 23.4% and 45.8 ± 3.2%, respectively, and p-STAT3 expression in advanced EMPD, non-invasive EMPD and NS were 97.0 ± 2.9%, 83.2 ± 23.3% and 50.1 ± 6.7%, respectively. P-ATF2 and p-STAT3 expressions in EMPD were significantly higher than those in NS, indicating a possible contribution of these pathways to the tumor development. P-ATF2 and p-STAT3 expressions in advanced EMPD were significantly higher than those in non-invasive EMPD, possibly indicating that these pathways might also contribute to the tumor invasion and/or metastasis. We also found an exceptionally high positive correlation between p-ATF2 and p-STAT3 expressions in EMPD. Conclusions: P-ATF2 and p-STAT3 are concordantly overexpressed in EMPD and their expressions may possibly be associated with the tumor stage. [ABSTRACT FROM AUTHOR]

Background Specificity protein 1 (Sp1) is a transcription factor and shown to be a sequence-specific DNA-binding protein that activate a broad and diverse spectrum of mammalian gene, such as vascular endothelial growth factor (VEGF) gene. But the expression of Sp1 and VEGF has not previously been investigated in extramammary Paget's disease (EMPD). Methods To investigate the expression of Sp1 and VEGF proteins in EMPD and to assess their relationships and potential contribution to malignant transduction of EMPD, paraffin-embedded EMPD specimens (35 tissue samples from 33 patients with primary EMPD, including two samples of metastatic lymph nodes from two patients) were subjected to immunohistochemical staining for Sp1 and VEGF. Results All of the 35 EMPD specimens, including all of six invasive EMPD and two metastatic lymph node specimens, showed strong nuclear positive staining for Sp1 and strong cytoplasmic positive staining for VEGF. The expression levels (% positive cells) of Sp1 and VEGF in EMPD were significantly higher than those of normal skin (NS). There was a significantly high correlation between expression levels of Sp1 and VEGF in EMPD. Conclusions The present study reveals that the concordant over-expression of Sp1 and VEGF may play a pivotal role in the tumorigenesis and further malignant transduction of EMPD. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK) is a tyrosine kinase which is at the crossroad of extracellular signal-regulated kinase-1/2 (ERK1/2), PI3K/Akt, MAPK and JAK/STAT signaling pathways. We have previously reported that p-ERK1/2, p-Akt, p38MAPK and p-STAT3 are overexpressed in extramammary Paget’s diseases (EMPD), this study aimed to examine the expression of phosphorylated (p)-FAK and p-ERK1/2 proteins in EMPD and to evaluate the relationships among them. Paraffin-embedded EMPD specimens (35 tissue samples from 33 patients with primary EMPD, including two samples of metastatic lymph nodes from two of the 33 patients) were subjected to immunohistochemical staining for p-FAK and p-ERK1/2. All of the 35 EMPD specimens, including all of six invasive EMPD and two metastatic lymph node specimens, showed cytoplasmic overexpression of p-FAK and nuclear overexpression of p-ERK1/2. The expression levels (% positive cells) of p-FAK and p-ERK1/2 (88.34 ± 14.66 and 91.26 ± 11.21%) in EMPD were significantly higher than those in normal skin (22.38 ± 2.13 and 29.00 ± 4.44%), respectively. The expression levels of p-FAK (95.38 ± 4.57%) and p-ERK1/2 (96.25 ± 5.01%) in the advanced EMPD showed slightly higher than that in the non-invasive EMPD (86.26 ± 15.99 and 89.78 ± 12.15%), respectively. There exhibited a significantly high positive correlation between expression levels of p-ERK1/2 and p-FAK in EMPD. The present study shows that the concordant overexpression of p-FAK and p-ERK1/2 in EMPD which is associated with the grade of malignancy of EMPD, indicating that p-FAK and p-ERK1/2 may play pivotal roles in the tumorigenesis and further malignant transduction of EMPD. [ABSTRACT FROM AUTHOR]

The model of membranous glomerulonephritis (MGN) in rats was successfully established using self-made cationic bovine serum albumin (C-BSA) and treated with Huangdan Decoction (HDD) and Tripterygium Wilfordii Co. tablet (TW). Results indicated that the levels of urinary protein, blood urea nitrogen (BUN) and serum creatinine (Scr) in treated groups (groups A, B and C) were significantly decreased as compared with the control group (group D) ( P<0. 01). By light and electron microscope and immunofluorescent technique, the damage to kidney in groups A, B and C was found much milder than that in group D with lesion in group A being slightest. These findings suggest that HDD and TW may alleviate the pathological lesions of MGN, prevent or retard its progression, and have remarkable therapeutic effects on MGN. [ABSTRACT FROM AUTHOR]