Objective:To investigate the role of microglial polarization modulated by triggering receptor expressed on myeloid cells 2/insulin-like growth factor-1(TREM2/IGF-1) in hypertensive model mice exposed to diesel exhaust particulate matter (DPM), with a focus on its implications for anxious- and depressive-like behaviors.Methods:SPF-grade male C57BL/6J mice were divided into the control group, the hypertension group, the DPM group, and the hypertension+ DPM group according to the principle of weight-matching, with 10 mice in each group. The hypertension model was established by intraperitoneal injection of angiotensin Ⅱ (AngⅡ) in hypertension group and hypertension+ DPM group, and mice in the control group and DPM group were intraperitoneally injected with an equivalent amount of 0.9% NaCl solution.DPM suspension was instilled into the nasal cavity of the mice in DPM group and hypertension+ DPM group(1 μg/μL, 10 μL, once a day for 56 days).Behavioral tests, including the sucrose preference test, tail suspension test, elevated plus maze test, and open field test, were conducted to evaluate anxious- and depressive-like behaviors.TREM2-overexpressing BV2 cell model was established through plasmid transfection technology.Western blot was applied to measure the protein expression of IL-1β, IL-6, TNF-α, iNOS, Arg-1, TREM2 and IGF-1.SPSS 23.0 software was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for post-hoc testing. Results:(1)There were statistically significant differences in the sucrose preference rate, immobility time in the tail suspension test, percentage of time and number of entries into the open arms in the elevated plus maze, as well as the total distance, percentage of time spent in the central area in the open field test among the four groups of mice( F=22.82, 21.60, 36.17, 20.99, 5.85, 13.24, all P<0.01).The sucrose preference rate, percentage of time spent in the open arms, percentage of number of entries into the open arms, total distance and percentage of time spent in the central area of the DPM group and the hypertension group were lower than those of the control group( P<0.05), while the immobility time of the two group was higher than that of the control group( P<0.05). The sucrose preference rate((55.62±4.46)%) and percentage of time spent in the open arms((4.17±0.62)%) of the hypertension+ DPM group were lower than those of the DPM group((60.78±3.21)%, (6.44±0.89)%) and the hypertension group((66.26±4.25)%, (6.53±1.29)%)(all P<0.05), while the immobility time((155.42±12.50)s) was higher than that of the DPM group((129.03±5.43)s) and the hypertension group((129.28±10.55)s)(both P<0.05).(2)Western blot analysis revealed statistically significant differences in protein expression of IL-1β, IL-6, TNF-α, iNOS, Arg-1, and TREM2/IGF-1 in the medial prefrontal cortex(mPFC) among the four experimental groups( F=12.23, 10.51, 33.89, 145.40, 11.85, 15.56, 33.11, all P<0.05).The hypertension+ DPM group demonstrated significantly higher protein expression of IL-1β and IL-6 compared to the hypertension group (all P<0.05). Relative to the hypertension+ DPM group, TNF-α and iNOS protein expression was elevated in both the hypertension group and DPM group, whereas Arg-1 protein expression was lower in the hypertension group(all P<0.05). Additionally, TREM2 and IGF-1 protein expression in the hypertension and DPM groups were lower than those in the control group but higher than those in the hypertension+ DPM group(all P<0.05).(3)The protein expressions of IL-1β, IL-6 and TNF-α in BV2 cells of the DPM+ AngⅡ-TREM2 overexpression group were lower than those of the DPM+ AngⅡ group. The expression of iNOS was lower than that in the DPM+ AngⅡ group, while the expression of Arg-1 was higher than that in the DPM+ AngⅡ group(all P<0.05). Conclusion:DPM exposure aggravates anxious- and depressive-like behaviors in hypertensive model mice, with TREM2/IGF-1-regulated microglial polarization playing a significant role in this process.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Spleen-stomach damp-heat syndrome is currently the most prevalent TCM pattern in patients with chronic atrophic gastritis (CAG), with internal damp-heat accumulation regarded as a key factor contributing to its prolonged and refractory course. This syndrome represents a critical stage in the progressive pathogenesis of CAG, characterized by a deepening pathological evolution. Modern TCM practitioners generally agree that its core pathogenesis lies in "deficiency in root and excess in superficiality, with internal damp-heat retention", and emphasize a treatment strategy that combines eliminating pathogenic factors and reinforcing the body's healthy qi through dynamic syndrome differentiation. Chinese materia medica used in treating CAG with spleen-stomach damp-heat syndrome can effectively relieve clinical symptoms, improve the internal damp-heat environment, mitigate gastric mucosal atrophy and intestinal metaplasia, and delay the inflammation-to-cancer transformation. Its mechanisms may involve eradication of Helicobacter pylori, repair of gastric mucosal injury, regulation of immune inflammatory response and other aspects, which has the advantages of multi-channel and multi-target.

Objective:To investigate the role of microglial polarization modulated by triggering receptor expressed on myeloid cells 2/insulin-like growth factor-1(TREM2/IGF-1) in hypertensive model mice exposed to diesel exhaust particulate matter (DPM), with a focus on its implications for anxious- and depressive-like behaviors.Methods:SPF-grade male C57BL/6J mice were divided into the control group, the hypertension group, the DPM group, and the hypertension+ DPM group according to the principle of weight-matching, with 10 mice in each group. The hypertension model was established by intraperitoneal injection of angiotensin Ⅱ (AngⅡ) in hypertension group and hypertension+ DPM group, and mice in the control group and DPM group were intraperitoneally injected with an equivalent amount of 0.9% NaCl solution.DPM suspension was instilled into the nasal cavity of the mice in DPM group and hypertension+ DPM group(1 μg/μL, 10 μL, once a day for 56 days).Behavioral tests, including the sucrose preference test, tail suspension test, elevated plus maze test, and open field test, were conducted to evaluate anxious- and depressive-like behaviors.TREM2-overexpressing BV2 cell model was established through plasmid transfection technology.Western blot was applied to measure the protein expression of IL-1β, IL-6, TNF-α, iNOS, Arg-1, TREM2 and IGF-1.SPSS 23.0 software was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for post-hoc testing. Results:(1)There were statistically significant differences in the sucrose preference rate, immobility time in the tail suspension test, percentage of time and number of entries into the open arms in the elevated plus maze, as well as the total distance, percentage of time spent in the central area in the open field test among the four groups of mice( F=22.82, 21.60, 36.17, 20.99, 5.85, 13.24, all P<0.01).The sucrose preference rate, percentage of time spent in the open arms, percentage of number of entries into the open arms, total distance and percentage of time spent in the central area of the DPM group and the hypertension group were lower than those of the control group( P<0.05), while the immobility time of the two group was higher than that of the control group( P<0.05). The sucrose preference rate((55.62±4.46)%) and percentage of time spent in the open arms((4.17±0.62)%) of the hypertension+ DPM group were lower than those of the DPM group((60.78±3.21)%, (6.44±0.89)%) and the hypertension group((66.26±4.25)%, (6.53±1.29)%)(all P<0.05), while the immobility time((155.42±12.50)s) was higher than that of the DPM group((129.03±5.43)s) and the hypertension group((129.28±10.55)s)(both P<0.05).(2)Western blot analysis revealed statistically significant differences in protein expression of IL-1β, IL-6, TNF-α, iNOS, Arg-1, and TREM2/IGF-1 in the medial prefrontal cortex(mPFC) among the four experimental groups( F=12.23, 10.51, 33.89, 145.40, 11.85, 15.56, 33.11, all P<0.05).The hypertension+ DPM group demonstrated significantly higher protein expression of IL-1β and IL-6 compared to the hypertension group (all P<0.05). Relative to the hypertension+ DPM group, TNF-α and iNOS protein expression was elevated in both the hypertension group and DPM group, whereas Arg-1 protein expression was lower in the hypertension group(all P<0.05). Additionally, TREM2 and IGF-1 protein expression in the hypertension and DPM groups were lower than those in the control group but higher than those in the hypertension+ DPM group(all P<0.05).(3)The protein expressions of IL-1β, IL-6 and TNF-α in BV2 cells of the DPM+ AngⅡ-TREM2 overexpression group were lower than those of the DPM+ AngⅡ group. The expression of iNOS was lower than that in the DPM+ AngⅡ group, while the expression of Arg-1 was higher than that in the DPM+ AngⅡ group(all P<0.05). Conclusion:DPM exposure aggravates anxious- and depressive-like behaviors in hypertensive model mice, with TREM2/IGF-1-regulated microglial polarization playing a significant role in this process.

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
Rats ; Animals ; Hyperalgesia/metabolism* ; Sleep Deprivation/metabolism* ; Rats, Sprague-Dawley ; Periaqueductal Gray/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Pain, Postoperative/pathology*

Objective:To investigate the roles of N6-methyladenosine (m 6A) modification in regulating RP11-426A6.5 in the development of laryngeal squamous cell carcinoma (LSCC). Methods:The methylation and expression levels of lncRNAs were identified and important lncRNAs were screened utilizing long non-coding RNA (lncRNA) m 6A methylation microarray. Cancer and para cancer tissue samples were taken from 48 LSCC patients hospitalized to the Department of Otolaryngology-Head and Neck Surgery of the Second Affiliated Hospital of Harbin Medical University between January and September 2017. Expression profiling microarray was performed in 3 of 48 LSCC samples, and methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR) and quantitative real-time fluorescent PCR (qRT-PCR) were performed in the remaining 45 LSCC samples to verify the m 6A modification and expression levels of RP11-426A6.5. Correlations between RP11-426A6.5 and clinical factors were anlysed. Laryngeal cancer cell line with low expression of RP11-426A6.5 was created in vitro using RNA interference (RNAi) technology. The 5-Ethynyl-2′-deoxyuridine (EdU) cell proliferation experiment, wound healing experiment, and transwell invasion experiment were used respectively to measure the proliferation, migration, and invasion of LSCC cells. The effect of RP11-426A6.5 down-regulation on the growth of transplanted tumors in vivo was verified by nude mice tumorigenesis assay. The Cancer Genome Atlas (TCGA) database and sequence-based RNA adenosine methylation site predictor (SRAMP) website were used to predict the enzymes and corresponding methylation sites. MazF digestion was chosen to validate the binding sites. RNAi technology was used to observe the changes in cell function after interfering with the expression of the corresponding genes of the modified enzymes. MeRIP-qPCR was used to detect the level of RP11-426A6.5 m 6A cell line treated with actinomycin D was used to observe the stability of RP11-426A6.5. Results:RP11-426A6.5 methylation and expression levels were significantly higher in LSCC tissues than those in paracancerous tissues (methylation levels: 23.828±4.975 vs 20.280±3.607; expression levels: 1.197±0.314 vs 1.015±0.170, all P values<0.05). RP11-426A6.5 expression levels were closely correlated with T stage (T1-2: 1.081±0.298 vs T3-4: 1.306±0.292, χ 2=5.35, P<0.05). The postoperative survival of patients with high RP11-426A6.5 expressions was significantly lower than that of patients with low RP11-426A6.5 expression ( P=0.046). Assays in vitro and in vivo showed that the downregulation of RP11-426A6.5 significantly decreased the proliferation, migration, and invasion abilities of LSCC cells and the growth of transplanted tumors. The binding of methyltransferase-like 3 (METTL3), an m 6A-modified enzyme, to the corresponding methylation site of RP11-426A6.5 enhanced its stability and mediated its regulation of malignant behaviors of LSCC cells. Conclusions:RP11-426A6.5 can regulate the malignant behaviors of LSCC cells, which is mediated by the m 6A modification process involving in the methyltransferase METTL3.

Objective:To explore the feasibility and precautions of laparoscopic pyeloplasty for children with hydronephrosis combined with renal trauma.Methods:The clinical data of 6 cases with hydronephrosis and renal trauma admitted to the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from August 2016 to August 2019, aged from 5 to 11 years old (average age 7 years old) were reviewed.These patients had suffered renal trauma for 1 to 4 days.All patients had the symptoms of pain in the affected kidney, and 4 patients had hematuria.The renal pelvis diameter of all patients was more than 25 mm.The patients underwent laparoscopic pyeloplasty and renal rupture repairment, with the ureteral stent, perirenal drainage tube and catheter placed inside the body during the operation.Results:All operations were completed successfully without any blood transfusion and open surgery.Intrao-perative time was from 2.5 to 3.5 hours.Two cases had renal parenchymal contusion in the front lower pole of kidneys and 4 cases in the lateral lower pole.Five cases had renal cortex and pelvis rupture, and 1 case had renal cortical fracture and subcapsular hematoncus.After the operation, the perinephric drainage tube was pulled out in 3 to 5 days, the catheter was pulled out in 7 to 10 days, and the ureteral stent was removed in 6 to 8 weeks.All children recovered well and hydronephrosis was ameliorated.The glomerular filtration rates and fractional renal function were all improved.Conclusions:One stage laparoscopic pyeloplasty is safe and effective for the treatment of hydronephrosis with renal trauma in children.Renal trauma in children usually occurs at the lower pole of the kidney.Early operation is needed if hydronephrosis is aggravated and symptoms are not relieved after the trauma.Intraoperative impairment of renal parenchymal rupture can be conducted.For intraoperative bleeding in grade 3 renal injury, renal parenchyma suturation and removal of necrotic renal tissue should be adopted to arrest bleeding.

Objective:To evaluate the effect of esketamine on acute kidney injury (AKI) in the rats with sepsis and the role of autophagy.Methods:Forty SPF healthy adult male Sprague-Dawley rats, weighing 200-240 g, were divided into 5 groups ( n=8 each) by a random number table method: control group (Con group), esketamine group (Con+ Ket group), sepsis group (lipopolysaccharide [LPS] group), sepsis plus esketamine group (LPS+ Ket group), and sepsis plus esketamine plus 3-methyladenine (3MA) group (LPS+ Ket+ 3MA group). The model of AKI was established by intraperitoneal injection of LPS in anesthetized rats.Normal saline 10 ml/kg was intraperitoneally injected in Con group.In Con+ Ket group, normal saline 10 ml/kg was intraperitoneally injected, and 30 min later esketamine 10 mg/kg was injected via the tail vein.LPS 10 mg/kg was intraperitoneally injected in LPS group.In LPS+ Ket group, LPS 10 mg/kg was intraperitoneally injected, and 30 min later esketamine 10 mg/kg was injected via the tail vein.In LPS+ Ket+ 3MA group, LPS 10 mg/kg was intraperitoneally injected, and 30 min later esketamine 10 mg/kg and 3-MA 15 mg/kg were injected via the tail vein.The rats were anesthetized at 24 h after intraperitoneal injection of LPS and then sacrificed, and renal tissues were removed for microscopic examination of the pathological changes which were scored and for determination of contents of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay) and expression of LC3, P62 and Beclin-1 (by Western blot). Results:Compared with Con group, the score for pathological damage to renal tissues and contents of NLRP3, ASC, caspase-1, IL-1β and IL-18 were significantly increased, LC3-Ⅱ/LC3-Ⅰ ratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of P62 was up-regulated in LPS group ( P<0.05). Compared with LPS group, the score for pathological damage to renal tissues and contents of NLRP3, ASC, caspase-1, IL-1β and IL-18 were significantly decreased, LC3-Ⅱ/LC3-Ⅰ ratio was increased, the expression of Beclin-1 was up-regulated, and the expression of P62 was down-regulated in LPS+ Ket group ( P<0.05). Compared with LPS+ Ket group, the score for pathological damage to renal tissues and contents of NLRP3, ASC, caspase-1, IL-1β and IL-18 were significantly increased, LC3-Ⅱ/LC3-Ⅰ ratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of P62 was up-regulated in LPS+ Ket+ 3MA group ( P<0.05). Conclusion:Esketamine can reduce AKI and autophagy is involved in the process, which is related to inhibiting the activation of NLRP3 inflammasomes and decreasing inflammatory responses in rats with sepsis.

Objective:To evaluate the therapeutic characteristics of laparoscopic repair in children with ure-terovesical junction malformation through internal or external bladder.Methods:From February 2018 to August 2019, 29 cases of hydronephrosis combined with ureter expansion treated in the First Affiliated Hospital of Zhengzhou University, with 17 boys and 12 girls confirmed through the preoperative examinations.Inspection results revealed 15 cases of ureteropelvic junction obstruction, 12 cases of vesicoureteral reflux, and 2 cases of single ectopic ureter.Totally, 21 cases were treated by pneumovesical laparoscopic Cohen means, including 17 unilateral cases and 4 bilateral cases, 5 cases of ureterocele, and 8 cases of ureteral clipping.A total of 8 cases were treated by laparoscopic Lich -Gregoir surgical treatment, including 7 unilateral cases and 1 bilateral case.Meanwhile, 4 cases of ureteral clipping were performed among them.There was 1 case of duplex kidney with the ectopic upper ureter outside iliac blood vessels, 1 case of bilateral cryptorchidism and 1 case of unilateral cryptorchidism.Ureteral stents were implanted for those with ureteral tailoring.The catheters were removed 7 days after operation, and the indwelling ureteral stents were removed by cystoscope under general anesthesia after about 6 weeks.Results:All the cases with hydronephrosis and ureteral dilatation were completed in laparoscopic surgery, without open surgery or blood transfusion, 21 cases were treated by pneumovesical laparoscopic Cohen means, with the average time being 1.8 hours in unilateral side and 2.8 hours in bilateral sides.At the same time, 8 cases were treated by laparoscopic Lich-Gregoir means, with the unilateral average time being 1.7 hours and bilateral time being 3.0 hours.All cases were followed up at an average month of 9 (4-20 months), and all children underwent voiding cystourethrography 4 months after the operations.The voiding cystourethrogram(VCUG) of all the cases was confirmed successfully, with only 1 case of vesicoureteral reflux in level Ⅲ, and their hydronephrosis were relieved.There was no vesicoureteral reflux in the others.The short-term urinary retention occurred in 1 patient with bilateral ureteral reimplantation in Lich-Gregoir group, and the symptom disappeared after 1 week of indwelling catheterization.Among them, 1 patient in Cohen group had hematuria that disappeared gradually for 4 days after surgery.There were no significant differences in operation time and postoperative recovery between the two groups.The length of hospital stay in laparoscopic Lich -Gregoir group was slightly longer than that in pneumovesical laparoscopic Cohen group.Conclusions:As for children with ureterovesical junction malformation, laparoscopic Lich-Gregoir surgery is suitable for the ectopia of ureter opening, overexpansion of ureter, and other abdominal malformation complicated and expansive ureter without tortuosity.Pneumovesical laparoscopic Cohen surgery is suitable for hydronephrosis and ureteral expansion with ureterocele, especially with the symptom of dysuria, and ureteral tortuosity obviously.The two ways are safe and reliable, and the advantages and disadvantages should be weighed before being chosen.

Objective:To explore the reasons for the retention of long time testicular torsion and the surgical selections of contralateral testis in children.Methods:The data of children with acute scrotal emergencies treated by the First Affiliated Hospital of Zhengzhou University from August 2016 to August 2019 were retrospectively analyzed.All the testicular torsion was included in the study sequence to summarize the clinical characteristics of the testicle that could be saved and different treatment methods adopted in the contrary side according to the anatomy of testes.Results:A total of 80 children with testicular torsion were included in the study.The onset time ranged from 2 hours to 15 days.All patients came to the hospital with unilateral scrotal pain or inguinal pain, including 74 cases of unilateral testicular torsion and 6 cases of cryptorchidical testicular torsion.All the children were treated with surgery.Orchiectomy was performed in 69 cases of testicular necrosis, and 11 cases were saved, among which 4 cases took a long time for testicular torsion, the main reason for the retention was the longer spermatic cord in the tunica vaginalis.Of the 80 healthy testes, the adhesion of the testis to tunica vaginalis was normal in 63 cases and abnormal in 17 cases.There were 20 children (including 5 children with abnormal anatomy) were routinely treated with partial removal of the tunica vaginalis and orchiopexy.Among the remaining 60 cases, 12 cases with abnormal adhesion of the testis to tunica vaginalis underwent partial removal of the tunica vaginalis and orchiopexy, and the other 48 cases with normal anatomy received the testis examination and the original incision closure.During the follow-up of 80 cases, 5 cases of the 11 children with the testis preserved returned to normal, 6 cases of them showed atrophy to varying degrees, and no discomfort such as torsion or pain was found in all the healthy testes.Conclusions:The long spermatic cord in the tunica vaginalis is the reason for long time testicular torsion in children with the testis saved.It buys time for the rescue of their testes.Orchiopexy is not necessary for those who have normal anatomy of the healthy testes, while partial removal of the tunica vaginalis and orchiopexy are recommended for patients with bell clapper anomaly.