Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

Quantitative image features of gadoxetic acid-enhanced MRI for predicting glypican-3 expression of small hepatocellular carcinoma ≤3 cm.

AIM: To explore the value of quantitative image features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting Gglypican-3 (GPC3) expression of single hepatocellular carcinoma (HCC) ≤3 cm. MATERIALS AND METHODS: One hundred and forty-nine patients with histopathologically confirmed HCC were included retrospectively. Quantitative image features and clinicopathological parameters were analysed. The significant predictors for GPC3 expression were identified using multivariate logistic regression analyses. Nomograms were constructed from the prediction model and the progression-free survival (PFS) rate was evaluated by the Kaplan-Meier method. RESULTS: The tumour-to-liver signal intensity (SI) ratio on the hepatobiliary phase (HBP; odds ratio [OR] = 0.004; p=0.001), serum alpha-fetoprotein (AFP) > 20 ng/ml (OR=6.175; p<0.001), and non-smooth tumour margin (OR=4.866; p=0.002) were independent significant factors for GPC3 expression. When the three factors were combined, the diagnostic specificity was 97.7% (42/43). The nomogram based on the predictive model performed satisfactorily (C-index: 0.852). Kaplan-Meier curves showed that patients with GPC3-positive HCCs have lower PFS rates than patients with GPC3-negative HCCs (Log-rank test, p=0.006). CONCLUSION: The tumour-to-liver SI ratio on the HBP combined with serum AFP >20 ng/ml and non-smooth tumour margin are potential predictive factors for GPC3 expression of small HCC ≤3cm. GPC3 expression is correlated with a poor prognosis in HCC patients.

[Association between depression tendency and cognitive trajectory in the elderly in rural area in China].

Objective: To explore cognitive trajectory and its association with depression tendency in the elderly in rural area in China. Methods: Based on the data of the rural elderly aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018, unconditional and conditional latent variable growth curve models were constructed to analyze the mini-mental state examination (MMSE) score trajectory and its association with depression tendency in the elderly. Results: A total of 1 788 elderly persons were included, and 19.1% of them had a depression tendency. The average MMSE score of those with and without a depression tendency at baseline survey were 26.62±3.54 and 27.59±3.17 respectively. The rate of MMSE score decline was 0.52 points (P<0.05). Before and after controlling covariates, the initial score was 0.84 points lower (P<0.05) and 0.81 points lower (P<0.05) in those with depressive tendency than in those without depressive tendency respectively, furthermore, the decline rate of MMSE score was 0.33 points lower (P<0.05) and 0.40 points lower (P<0.05) in those with depressive tendency than in those without respectively. Conclusions: The depression tendency in the elderly in rural area in China was associated with the cognitive function change trajectory, with those with depression tendency had lower-level trajectory. Attention should be paid to the mental health of the elderly in rural area to prevent dementia and slow its development.

[Differences of water barrier function between keloid and its surrounding normal skin in patients with keloids and its related mechanism].

Objective: To compare the differences of water barrier function between keloids and its surrounding normal skin in patients with keloids, and to explore the primary mechanism. Methods: A cross-sectional observational study was conducted. From October 2020 to March 2021, 30 patients with keloids who met the inclusion criteria visited Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 18 females and 12 males, aged 20-48 years. The transepidermal water loss (TEWL) of their keloids and the surrounding normal skin of the 30 patients were measured by multi probe adapter on the reception day. The keloid tissues and normal skin of 5 patients after keloid repair surgery were processed for hematoxylin-eosin staining to measure the thickness of epidermis. Immunohistochemistry was performed on samples from 3 of those 5 patients to detect the expressions of cytokeratin-10, involucrin, and filaggrin in keloids and normal skin. Data were statistically analyzed with paired sample t test and independent sample t test. Results: On the reception day, the TEWL of keloids of 30 patients was 9.0 (6.9, 13.4) g·m-2·h-1 and the TEWL of the normal skin was 8.1 (6.4, 18.1) g·m-2·h-1, between which the difference was not statistically significant (t=0.44, P>0.05). After keloid repair surgery, the thickness of epidermis in the keloids of 5 patients was (194±44) µm, which was significantly thicker than that of the normal skin (44±11) µm, (t=6.88, P<0.01). Furthermore, increased keratinocytes, lack of normal epidermal ridge structures, and thickened stratum corneum were observed in the keloid area. After keloid repair surgery, the expression level of cytokeratin-10 in keloids was significantly lower than that in normal skin of 3 patients (t=8.50, P<0.01), but there were no statistically significant differences in the expression levels of involucrin or filaggrin between keloids and normal skin (with t values of 0.07 and 0.96, respectively, P>0.05). Conclusions: Keloid tissue from patients with keloids displays increased number of keratinocytes and thickened epidermis. But the water barrier function in keloid area is similar to the surrounding normal skin, suggesting that TEWL may not be the main mechanism lead to the persistent development of keloids.

Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets.

Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.

[Comprehensive measurement and quantification of bio-mechanical properties of the temporomandibular joint disc].

Objective: To comprehensively investigate the biomechanical properties of the temporomandibular joint (TMJ) disc and to perfect the mechanical testing system of the TMJ disc by conducting tests of compression, tension, cyclic compression, cyclic tension, creep and friction. Methods: Fifteen fresh goat heads (weighing 2.5-3.0 kg) were purchased from the market. They were all ordinary goats (9-12 months old, body weighing 18-21 kg) regardless of gender. Bilateral articular discs (a total of 30) were dissected within 30 minutes after execution. According to the national standard for mechanical testing of viscoelastic materials, fresh TMJ disc specimens of goat were prepared and tests were carried out in physiological conditions. The universal mechanical testing machine was utilized to test biomechanical properties of TMJ discs. Results: The compressive modulus of TMJ discs was (8.41±2.12) MPa and the tensile modulus was (9.54±3.26) MPa. The mechanical characteristics would be irreversibly altered once the load exceeded the physiological range. In addition, it underwent apparent creep relaxation under continuous strain (0.5 MPa or 3.0 MPa) and the surface friction coefficient of the TMJ discs (0.015+0.011) was much lower than that of general viscoelastic materials. Conclusions: The TMJ disc was a bio-viscoelastic structure with excellent tensile and compressive properties and its surface was extremely smooth in wet conditions.

[Role of histone demethylase KDM6B in HBx-mediated podocyte-macrophage transdifferentiation].

Objective: To explore the expression of lysine (k)-specific demethylase 6B (KDM6B) in the renal tissues of hepatitis B virus-associated glomerulonephritis (HBV-GN) patients and human podocytes transfected with hepatitis B virus X (HBx) gene, and its role in HBx-mediated podocyte-macrophage transdifferentiation (PMT). Methods: Forty-eight patients diagnosed as HBV-GN by renal biopsy from 2013 to 2018 at the Shanghai Jiaotong University Affiliated First People's Hospital were included in this study. Thirty patients with primary glomerulonephritis (PGN) and fifteen patients with renal tumor were chosen as control group. The expression of KDM6B and macrophage marker F4/80 in renal tissues of HBV-GN patients was observed by immunofluorescence and immunohistochemistry. The association between kidney KDM6B levels and clinical features of HBV-GN patients was analyzed. The expression of KDM6B, F4/80, major histocompatibility complex (MHC)-Ⅱ and CD40 in the podocytes was detected by Western blotting. The contents of interferon-γ (IFN-γ) and interleukin-6 (IL-6) in the supernatant were determined by enzyme-linked immunosorbent assay (ELISA). The small interfering RNA of KDM6B (KDM6B siRNA) was used to silence the expression of KDM6B and the protein levels of KDM6B, F4/80 and tri-methylation of lysine 27 of histone H3 (H3K27me3) induced by HBx gene transfection were detected by Western blotting. Results: Renal KDM6B expression was significantly increased in HBV-GN patients compared to normal control (0.022±0.004 vs 0.006±0.002, P=0.006). There was no significant difference in the positive rate of KDM6B among different pathological types of HBV-GN (P=0.139). Moreover, co-expression of KDM6B and F4/80 could be observed in the podocytes of HBV-GN patients. Patients with estimated glomerular filtration (eGFR)<60 ml·min-1·(1.73 m2)-1or proteinuria ≥ 3.5 g/day had a significantly higher renal KDM6B expression compared to control groups (all P<0.05). In addition, the expression of KDM6B, F4/80, MHC-II and CD40 was significantly up-regulated in the podocytes transfected with HBx gene (all P<0.05). The content of IFN-γ and IL-6 in the supernatant was significantly increased (all P<0.05). After gene silencing of KDM6B, the expression of F4/80 induced by HBx in the podocytes was significantly down-regulated, while the level of H3K27me3 was significantly increased (both P<0.05). Conclusions: HBx could induce KDM6B expression in podocytes and initiate PMT, thereby involving in the dysfunction of immune microenviroment in the renal tissues of HBV-GN.

Effect of alfalfa hay and starter feed supplementation on caecal microbiota and fermentation, growth, and health of yak calves.

The caecum is the primary site where microbial fermentation and acidosis occurred. The supplementation of starter feed and alfalfa hay has the potential to influence caecal microbiota and then affect caecal fermentation. This study aims to investigate the effect of starter feed and alfalfa hay supplementation on caecal microbiota, immune homeostasis, and growth of preweaning yaks. Twenty 30-day-old male yak calves were randomly assigned to four groups, which separately fed with milk replacer (CON group), milk replacer with alfalfa hay (A group), milk replacer with starter feed (S group), and milk replacer with starter feed plus alfalfa hay (SA group) throughout the trial. Growth performance and plasma physiological and biochemical indicators were measured every 30 days. Calves were sacrificed at 120 days of age. The caecal contents were collected for measuring pH and contents of volatile fatty acids (VFAs) and lipopolysaccharide (LPS) and for characterizing caecal microbiota. The results indicated that individual or simultaneous supplementation with alfalfa hay and starter feed all significantly increased the BW, body height, body length, and chest girth of yak calves. However, supplementation with starter feed significantly increased plasma cortisol, nitric oxide, tumor necrosis factor-α, and interferon-γ concentrations and the ratio of aspartate aminotransferase to alanine aminotransferase of yak calves when compared with the control and alfalfa hay feeding groups, while the co-supplementation of starter feed and alfalfa hay could significantly decrease these inflammation-related indices when compared with the starter feeding group. Sequencing of the 16S rRNA gene showed that starter feed and alfalfa hay separately stimulated the proliferation of starch-decomposing and cellulose- or hemicellulose-decomposing bacteria. This also significantly increased the levels of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate in the caecal contents. Furthermore, compared with the S and CON groups, the significantly increased genera of Desulfobulbus, Olsenella, Pseudoflavonifractor, and Stomatobaculum in the SA and A groups were beneficial to the immune homeostasis, and the significantly decreased Blautia, Clostridium IV, Bacteroides, Eubacterium, Clostridium XVIII, and Mogibacterium in the SA and A groups were related to the reduced caecal lactate and LPS contents, the decreased inflammatory reaction, and the improved healthy hepatic condition of yak calves. In conclusion, milk replacer supplemented with alfalfa hay and starter feed is recommended during preweaning to improve yak calf health and growth because this regimen promotes the growth and maintains the immune homeostasis of yak calves.

LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma.

OBJECTIVE: The purpose of this study was to investigate the potential effects of LIM and Src homology 3 (SH3) protein 2 (LASP2) on nasopharyngeal carcinoma (NPC) and the relevant mechanism. PATIENTS AND METHODS: The expression of LASP2 in NPC patients and non-cancer patients in the control group was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The patients were divided into LASP2 high-expression group (n=30) and low-expression group (n=30), according to the median expression level of LASP2. Then, the expression of LASP2 was detected in the chosen cell lines by qRT-PCR. RESULTS: In qRT-PCR experiment, LASP2 was found up-expressed in NPC clinical samples and cell lines. Besides, LASP2 expression was associated with the clinical stage and distant metastasis of NPC. Next, the expression of LASP2 was downregulated by transfection of si-LASP using LipofectamineTM 3000 in 6-10B cells in vitro. The transfection effects of si-LASP2 were confirmed by qRT-PCR and Western-blot (WB) experiments. In supplementary experiments, decreased expression of LASP2 in cells could inhibit the cell biological functions, including invasion, migration, and epithelial-mesenchymal transition (EMT). CONCLUSIONS: This research discovers the promotion effect of LASP2 on NPC, suggesting that LASP2 could be used as a potential therapeutic target for NPC.

[Research value of 50 MHz high-frequency ultrasound on sonography of normal facial skin in adult].

Objective: To observe the differences in normal facial skin thickness and echo density by different ages and sites of healthy adults of the same sex using 50 MHz high-frequency ultrasound. Methods: From January to June 2019, 200 healthy adult volunteers with normal facial skin who were from Sichuan, Yunnan, Guizhou, and Chongqing and met the inclusion criteria were recruited by the Affiliated Hospital of Southwest Medical University with simple random sampling method, and then were included in this cross-sectional investigation study. Then 50 MHz high-frequency ultrasound was used to obtain skin ultrasonogram of volunteers' forehead, canthus, eyelid, and cheek. According to the ages, 100 female volunteers were divided into 20-29 years old (30 females), 30-39 years old (25 females), 40-49 years old (20 females), and 50-70 years old (25 females) groups; 100 male volunteers were divided into 20-29 years old (30 males), 30-39 years old (25 males), 40-49 years old (20 males), and 50-70 years old (25 males) groups. The thickness of full-skin, the upper dermal echo density, and the lower dermal echo density of the female and male volunteers'forehead, canthus, eyelid, and cheek were recorded respectively. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Bonferroni correction. Results: (1) The thickness of full-thickness skin in forehead, canthus, eyelid, and cheek of female and male volunteers in 20-29 years old group were (1.86±0.26), (1.36±0.11), (1.24±0.25), and (1.90±0.21) mm, (2.45±0.37), (1.64±0.19), (1.44±0.16), and (2.53±0.26) mm, respectively, in 30-39 years old group were (1.98±0.24), (1.43±0.13), (1.15±0.15), and (2.12±0.13) mm, (2.34±0.27), (1.63±0.27), (1.50±0.38), and (2.43±0.40) mm, respectively, in 40-49 years old group were (1.90±0.21), (1.43±0.18), (1.24±0.27), and (1.98±0.12) mm, (2.14±0.24), (1.54±0.25), (1.28±0.14), and (2.39±0.36) mm, respectively, in 50-70 years old group were (1.64±0.25), (1.36±0.19), (1.16±0.12), and (1.89±0.29) mm, (2.28±0.27), (1.73±0.25), (1.58±0.18), and (2.38±0.32) mm, respectively. There were no statistically significant differences between female volunteers in the 4 groups and male volunteers in the 4 groups in thickness of full-thickness skin in canthus, eyelid, and cheek (F=0.677, 0.666, 0.136, 0.697, 0.294, 0.888, P>0.05). The thickness of full-thickness skin in forehead and cheek of the female volunteers in the 4 groups and male volunteers in the 4 groups was similar (P>0.05), and was significantly higher than that of canthus and eyelid (P<0.05). The thickness of full-thickness skin in canthus and eyelid of female volunteers in 20-29 years old, 40-49 years old, and 50-70 years old group was similar (P>0.05), while thickness of full-thickness skin in canthus and eyelid of male volunteers in the 4 groups was similar (P>0.05). (2) The upper dermal echo density of forehead, canthus, eyelid, and cheek of female volunteers in 50-70 years old group was significantly lower than that in 20-29 years old and 30-39 years old groups (P<0.05). The upper dermal echo density of forehead, canthus, eyelid, and cheek of male volunteers in 50-70 years old group was significantly lower than that in 20-29 years old group (P<0.05). The upper dermal echo density of forehead, canthus, eyelid, and cheek of female and male volunteers in 20-29 years old and 30-39 years old groups was similar (P>0.05). The upper dermal echo density of forehead and cheek of female volunteers in 20-29 years old, 40-49 years old, and 50-70 years old groups was significantly lower than that of canthus and eyelid (P<0.05). The echo density of upper dermis of cheek of male volunteers in the 4 groups was significantly lower than that of canthus and eyelid (P<0.05). The upper dermal echo density of canthus and eyelid of female volunteers in the 4 groups and male volunteers in the 4 groups was similar (P>0.05), the upper dermal echo density of forehead and cheek was similar (P>0.05). (3) The lower dermal echo density of forehead, canthus, eyelid, and cheek of female volunteers in 50-70 years old group was significantly higher than that in 20-29 years old and 30-39 years old groups (P<0.05). The lower dermal echo density of forehead, canthus, eyelid, and cheek of male volunteers in 50-70 years old group was significantly higher than that in 20-29 years old group (P<0.05). The echo density of the lower dermis of forehead, eyelid, and cheek of female and male volunteers in 20-29 years old, 30-39 years old, and 40-49 years old groups was similar (P>0.05). The lower dermal echo density of forehead and cheek of female volunteers in the 4 groups was significantly lower than that of canthus and eyelid (P<0.05). The lower dermal echo density of forehead and cheek of male volunteers in 30-39 years old, 40-49 years old, and 50-70 years old groups was significantly lower than that of canthus and eyelid (P<0.05). The lower dermal echo density between canthus and eyelid and between forehead and check of female volunteers in the 4 groups and male volunteers in the 4 groups was similar (P>0.05). Conclusions: The 50 MHz high-frequency ultrasonography shows that the thickness of full-thickness skin of canthus, eyelid, and cheek is similar in all age groups of female and male adult volunteers with normal facial skin. In the same age group, the thickness of full-thickness skin of forehead and cheek of male and female volunteers is significantly higher than that of canthus and eyelid. The upper dermal echo density of forehead, canthus, eyelid, and cheek of female and male volunteers shows a decreasing trend with age, while the lower dermal echo density shows an increasing trend with age. In addition, the echo density of upper and lower dermis of canthus and eyelid was significantly higher than that of cheek in all the four age groups.

[Clinical effectiveness of super pulsed carbon dioxide fractional laser debridement surgery in treating chronic wounds].

Objective: To investigate the clinical effectiveness of super pulsed carbon dioxide fractional laser debridement surgery on the treatment of chronic wounds. Methods: From December 2018 to May 2019, 37 patients with chronic wounds who met the inclusion criteria were admitted to the Affiliated Hospital of Southwest Medical University for a prospective randomized controlled study. Using the random number table, the patients were divided into surgical debridement group (19 patients, 4 males and 15 females, aged (58±16) years, 25 wounds) and laser debridement group (18 patients, 9 males and 9 females, aged (58±10) years, 23 wounds). In patients of surgical debridement group, oedematous and aging granulation tissue was scraped from the wound by scalpel handle or curet, and the residual necrotic tissue was removed by sharp surgical instruments. In patients of laser debridement group, oedematous and aging granulation tissue and necrotic tissue was removed by super pulsed carbon dioxide fractional laser therapeutic machine, laser gasification debridement was performed repeatedly till fresh normal tissue layer observed. In patients of the two groups, according to the wound in the first 3 d after the first debridement, debridement dressing was performed twice at least as before, then wound debridement dressing was performed once every 1 to 4 days as before according to the wound conditions. The wound healing rates on 7, 14, 21, and 28 d after the first debridement were calculated. The positive rates of bacterial culture of wounds before and after the first debridement were calculated. The color and texture of the wound granulation tissue before the first debridement and on 7, 14, and 28 d after the first debridement were observed and scored. The pain scores before every debridement, during every debridement, and after every debridement dressing change were evaluated by visual analogue scale. The times of debridement dressing change were recorded. Data were statistically analyzed with two independent sample t test, analysis of variance for repeated measurement, Fisher's exact probability test, Mann-Whitney U test, and Bonferroni correction. Results: (1) On 7, 14, 21, and 28 d after the first debridement, the wound healing rates of patients in laser debridement group (29.5% (24.1%, 36.0%), 47.1% (42.7%, 62.4%), 71.4% (62.2%, 76.8%), and 88.6% (79.2%, 96.3%) were significantly higher than those of surgical debridement group (1.6% (1.0%, 12.8%), 12.7% (2.0%, 16.6%), 24.5% (8.9%, 45.5%), 43.9% (23.2%, 70.8%), Z=3.477, 3.553, 2.721, 2.193, P<0.05 or P<0.01). (2) Before the first debridement, the positive rates of bacterial culture of wounds in patients of laser debridement group and surgical debridement group were 92% (23/25) and 91% (21/23), respectively, which were similar (P>0.05). After the first debridement, the positive rate of bacterial culture of wounds of patients in surgical debridement group was 64% (16/25), which was significantly higher than 13% (3/23) of laser debridement group (P<0.01). (3) On 7, 14, and 28 d after the first debridement, the scores of color and texture of wound granulation tissue of patients in laser debridement group were significantly higher than those of surgical debridement group (Z=3.420, 5.682, 6.142, 4.461, 5.337, 4.458, P<0.01). (4) The pain scores during every debridement and after every debridement dressing change in patients of laser debridement group were significantly lower than those of surgical debridement group (t=2.847, 5.046, P<0.05 or P<0.01). (5) The time of debridement dressing change in laser debridement group was 8.0 (7.0, 10.0) times, which was significantly less than 10.0 (9.5, 12.5) times in surgical debridement group (Z=2.261, P<0.05). Conclusions: Compared with traditional surgical debridement method, super pulsed carbon dioxide fractional laser debridement surgery is more effective in treating patients with chronic wounds. Laser debridement makes the wound healing more efficiently with reduced pain and better infection control; significantly reduces the number of dressing changes, and is especially suitable for the wound treatment in outpatients.

MicroRNA-1247 inhibits the viability and metastasis of osteosarcoma cells via targeting NRP1 and mediating Wnt/ß-catenin pathway.

OBJECTIVE: Osteosarcoma (OS) is a common malignant bone tumor that poses a serious threat to the health of adolescents or children. A large number of studies have proposed the role of microRNAs (miRNAs) in OS, except for miR-1247. Therefore, this research was designed to explore the molecular mechanism of miR-1247 in OS. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot analysis was used to measure the expressions of miR-1247 and genes. The function of miR-1247 was investigated using Cell Counting Kit-8 (CCK-8) and transwell assays. The Dual-Luciferase reporter assay was used to explore the relationship between miR-1247 and neuropilin-1 (NRP1). RESULTS: MiR-1247 was downregulated in OS, which was related to the aggressive behavior of OS patients. Moreover, miR-1247 inhibited cell viability and metastasis in OS. At the same time, miR-1247 promoted apoptosis and inactivated the Wnt/ß-catenin pathway in OS. Furthermore, it was confirmed that NRP1 was a direct target of miR-1247. Upregulation of NRP1 attenuated the inhibitory effect of miR-1247 in OS. CONCLUSIONS: MiR-1247 played a suppressive role in OS by suppressing cell viability and metastasis.

[Retrospective cohort study on the correlation between high value of lactic acid and risk of death in 127 patients with extensive burn during shock stage].

Objective: To analyze the relationship between serum lactic acid value and risk of death in patients with extensive burn during shock stage and the related influencing factors. Methods: Clinical data of 127 patients (111 males and 16 females) with extensive burn admitted to Institute of Burn Research of the First Affiliated Hospital of Army Medical University from January 2009 to December 2013 and Department of Plastic Surgery and Burns of the Affiliated Hospital of Southwest Medical University from January 2016 to December 2018, who met the admission criteria, were retrospectively analyzed. The patients aged 21 to 62 years, with total burn area more than 50% total body surface area. All patients were treated with antishock therapy after admission. (1) According to the treatment outcome, the patients were divided into survival group (n=98) and death group (n=29). The gender, age, total burn area, partial-thickness burn area, full-thickness burn area, abbreviated burn severity index (ABSI), admission time after injury, number of patients with inhalation injury, number of patients with acute renal failure, and serum lactic acid values on admission and at post admission hour (PAH) 12, 24, 36, and 48 were recorded. (2) According to the optimal positive cut-off value of serum lactic acid 48 hours after admission, the patients were divided into high lactic acid group and normal lactic acid group. Age, gender, total burn area, indexes at PAH 48 including urea nitrogen, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total serum bilirubin, alkaline phosphatase (ALP), albumin, white blood cell count, platelet count, lymphocyte count, prothrombin time (PT), hematocrit value, oxygenation index, respiratory index (RI), the alveolar-arterial oxygen partial pressure difference, mean arterial pressure (MAP) at PAH 48, the average urine volume within 48 hours after admission, the total volume of intravenous fluid infusion within 48 hours after admission, the volume of fluid infusion per kilogram of body mass within the first 24 hours after admission, the volume of fluid infusion per one percent of body surface area per kilogram of body mass within the first 24 hours after admission, the volume of urine per kilogram of body mass per hour within the first 24 hours after admission, and the percentage of hospital death were recorded. Data were processed with t test, chi-square test, and Fisher's exact probability test. Cox regression analysis was used to screen independent risk factors affecting the prognosis of patients. Receiver operating characteristic curve (ROC) of serum lactic acid value at PAH 48 of 127 patients was drawn to predict patients' death and determine the optimal positive cut-off value. Multivariate logistic regression analysis was used to screen independent risk factors causing increase of serum lactic acid. Results: (1) There were significantly statistical differences in total burn area, full-thickness burn area, and ABSI of patients between survival group and death group (t=6.257, 4.476, 5.727, P<0.01), while other indexes between the two groups were close. (2) The serum values of lactic acid of patients in death group on admission and at PAH 12, 24, 36, and 48 were (4.00±0.28), (4.50±0.26), (4.02±0.31), (3.48±0.22), (3.40±0.19) mmol/L, respectively, which were significantly higher than those in survival group [(3.30±0.21), (3.20±0.19), (2.33±0.17), (1.85±0.18), (1.50±0.09) mmol/L, t=14.552, 29.603, 38.133, 40.648, 74.973, P<0.05 or P<0.01]. (3) Cox regression analysis showed that the serum value of lactic acid at PAH 48 was the independent risk factor affecting the prognosis of patients, with risk ratio of 1.853 and 95% confidence interval of 1.342-2.559, P<0.01. (4) The total area under ROC of serum value of lactic acid at PAH 48 to predict death of 127 patients was 0.811, with 95% confidence interval of 0.699-0.924, P<0.01. The optimal positive cut-off value of serum value of lactic acid was 1.75 mmol/L, with sensitivity of 75.0% and specificity of 79.5% for predicting death. (5) There were significantly statistical differences in total burn area, ALT, AST, ALP, PT, total serum bilirubin, total volume of intravenous fluid infusion within 48 hours after admission, volume of fluid infusion per kilogram of body mass within the first 24 hours after admission, and percentage of hospital deaths of patients between high lactic acid group (n=34) and normal lactic acid group (n=93), t=3.592, 6.797, 10.367, 2.089, 2.880, 4.517, 2.984, 4.044, χ(2)=58.498, P<0.05 or P<0.01, while other indexes were close between the two groups. (6) Multivariate logistic regression analysis showed that AST and total serum bilirubin were independent risk factors for increase of serum lactic acid, with odds ratios of 1.021 and 1.064 and 95% confidence intervals of 1.001-1.040 and 1.001-1.132, P<0.05. Conclusions: Serum value of lactic acid at PAH 48 can independently predict the death of patients with extensive burns. Liver injury is an important risk factor causing hyperlacticemia during burn shock stage. Widespread increase of vascular permeability and large amount of fluid resuscitation are the core factors leading to aggravation of abdominal organ injury.

[Analysis on prognosis and influencing factors of postoperative low anterior resection syndrome for rectal cancer patients undergoing laparoscopic anus-preserving radical resection].

Objective: To investigate the prognosis and influencing factors of postoperative low anterior resection syndrome (LARS) for rectal cancer patients undergoing laparoscopic sphincter-preserving radical resection. Methods: A retrospective case-control study was used in this study. Clinical data of 268 rectal cancer patients undergoing laparoscopic sphincter-preserving radical resection at Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2016 to January 2018 were retrospectively collected. Inclusion criteria: (1) operation procedure was total mesorectal excision (TME) and sphincter-preserving radical resection; (2) rectal cancer was confirmed by postoperative pathology; (3) age of patient was ≥ 18 years old. Exclusion criteria: (1) patient who had history of pelvic surgery and pelvic fractures, which would affect the anorectal function; (2) patient who had history of preoperative chronic constipation and irritable bowel syndrome, which would affect defecation; (3) patient who developed postoperative complications, such as anastomotic leakage, which would affect defecation function; (4) patient who received long-term use of drugs, which would affect the function of gastrointestinal tract or anus; (5) patient suffered from mental illness, who was unable to communicate properly; (6) patient who was lack of clinical data or had incomplete clinical data. Patients were followed up at 3, 6 and 12 months postoperatively, and LARS was diagnosed and graded according to the LARS score scale. The LARS score ranged from 0 to 42 points, and 0 to 20 was difined as no LARS, 21 to 29 was mild LARS, and 30 to 42 was severe LARS. LARS score >20 points at any time point was defined as postoperative LARS. Severe LARS transferring into mild LARS and mild LARS transferring into no LARS was defined as symptom improvement. Incidence and outcomes of LARS were evaluated. The factors associated with LARS outcomes were analyzed using χ(2) test and logistic regression model. Results: A total of 268 patients were enrolled. The incidence of LARS was 42.9% (115/268), 32.5% (87/268) and 20.1% (54/268) at 3, 6, and 12 months postoperatively respectively, and no new case of LARS was found after 3 months postoperatively. The incidence of mild LARS was 25.7% (69/268), 17.2% (46/268) and 8.6% (23/268) at 3, 6, and 12 months postoperatively respectively, and mild LARS incidence at 6 months was significantly lower than that at 3 months (χ(2)=5.857, P=0.016), and was significantly higher than that at 12 months (χ(2)=8.799, P=0.003). The incidence of severe LARS was 17.2% (46/268), 15.3% (41/268) and 11.6% (31/268) at 3, 6, and 12 months postoperatively respectively, without significant difference among 3 time points (all P>0.05). The improvement rate within one year after surgery in patients with mild LARS diagnosed at 3 months was significantly higher than that in patients with severe LARS (88.4% vs. 32.6%, χ(2)=38.340, P<0.001). Univariate analysis showed that female, distance from anastomosis to anal verge < 5 cm and tumor diameter ≥ 5 cm were associated with unsatisfied LARS outcomes (all P<0.05). Logistic regression analysis showed that distance from anastomosis to anal verge <5 cm was an independent risk factor for LARS outcome (OR=3.589, 95% CI: 1.163 to 2.198, P<0.001). Conclusions: The incidence of LARS after laparoscopic sphincter-preserving radical resection decreases with time. The improvement rate within postoperative 1-year of severe LARS is lower than that of mild LARS. Low anastomotic position may lead to impaired improvement of LARS.

Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. METHODS: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. RESULTS: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. CONCLUSIONS: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.

[Evaluation of bioceramic putty repairment in primary molars pulpotomy].

OBJECTIVE: To evaluate the clinical characteristics and effectiveness of bioceramic putty repairment (iroot BP Plus) used as pulp capping agents on pulpotomy in primary molars. METHODS: Forty primary molars were treated by pulpotomy with bioceramic putty repairmen as the pulp capping agents at the Third Clinical Division of Peking University School and Hospital of Stomatology, from September 2016 to September 2017. The children who were followed up over one year were selected as the subjects of this study. The teeth were checked clinically and radiographically during fixed intervals, and classified into one of five outcomes: N, H, P0, PX, PY. N, absence of clinical symptoms, and absence of apical radiolucency; H, absence of clinical symptoms, and nonpathologic radiographic change present; P0, absence of clinical symptoms, and pathologic change present, no need for treatment; PX, present or absence of clinical symptoms, pathologic change present treatment or extract immediately; PY, premature loss of deciduous tooth. Molars classified into N and H were regarded as successful, classified into P0, PX and PY were regarded as failed. RESULTS: Followed up for 12-24 months (the average follow up time was 16months), thirty four children were finally included, aged from 3.1 years to 8.5 yaers (the average age was 4.3 years), forty primary molars were included. Thirty four primary molars were included into N group, with absence of clinical symptoms, absence of apical radiolucency. Two molars were included into H group with physiological root absorption. One molar was included into P0group with absence of clinical symptoms butinternal absorption of the root. Three molars were included into PX group, with gingival fistula and apical radiolucency. None was included into PY group. Thirty six teeth got successful treatment, four molars failed. One year success rate of pulpotomy of primary molars using bioceramic putty repairment was 95%. CONCLUSION: Current evidence suggests that bioceramic putty repairment as a pulpotomy medicament showed satisfied clinical and radiographic result in pulpotomy of primary molars. Bioceramic putty repairment is an acceptable material when used in pulpotomy of primary molars.

IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma.

Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor-binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma. Enforced expression of IGFBP2 increased network formation of glioma cells in vitro by activating CD144 and MMP2 (Matrix Metalloproteinase 2). U251 cells with stable knockdown of IGFBP2 led to decreased VM formation and tumor progression in orthotopic mouse model. Mechanistically, IGFBP2 interacts with integrin α5 and ß1 subunits and augments CD144 expression in a FAK/ERK pathway-dependent manner. Luciferase reporter and ChIP assay suggested that IGFBP2 activated the transcription factor SP1, which could bind to CD144 promoter. Thus, IGFBP2 acts as a stimulator of VM formation in glioma cells via enhancing CD144 and MMP2 expression.