Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Objective To evaluate the application value of artificial intelligence mixed reality(AI-MR)technology in the planning of ultrasound-guided percutaneous nephrolithotomy(PCNL)for special types of complex upper urinary stones.Methods The prospective single-center,single-arm clinical study involved 15 patients with complex upper urinary stones undergoing ultrasound-guided PCNL during Aug.2022 and May 2023,including 9 male and 6 female,3 cases of pelvic ectopic kidney stones,5 cases of horseshoe kidney stones,3 cases of renal stones combined with spinal deformity,and 4 cases of transplant kidney stones.Based on preoperative computed tomography urography(CTU)data,digital three-dimensional reconstruction was performed,and AI-MR was used to project surgery-related three-dimensional images in real space to obtain"perspective"information of the surgical area.This facilitated preoperative design and planning,including target calyx,number of channels,and auxiliary measures.The compliance of target calyx and number of channels,stone clearance rate,total operation time,time required to establish the percutaneous renal channel,decrease in hemoglobin level,surgical complications,and postoperative hospital stay were analyzed.Results All 15 patients underwent preoperative planning using AI-MR and successfully completed one-stage ultrasound-guided PCNL.Based on the preoperative planning,we utilized S-PCNL alone or combined with Needle-perc or antegrade/retrograde FURS/RIRS.Among all patients,4 underwent single-channel S-PCNL,3 multi-channel S-PCNL,and 8 S-PCNL combined with Needle-perc or FURS.The compliance of target calyx and number of channels was 86.7％,the one-stage stone clearance rate was 80.0％,the average time for establishing the channel was(2.3±0.3)minutes,the average total operation time was(61.5±12.2)minutes,the mean decrease in hemoglobin level was(9.6±1.2)g/L,and the average postoperative hospital stay was(4.6±0.5)days.There were no Clavien-Dindo grade ≥ Ⅱ complications,such as blood transfusion,organ injury,or urosepsis.Conclusion Before surgery,AI-MR can be used to quantitatively analyze imaging data for patients with special types of complex upper urinary stones,which can achieve three-dimensional fluoroscopy effects,formulate surgical plans,optimize puncture paths,effectively avoid the risk of damage to surrounding organs,reduce complications,shorten treatment cycle and improve the first-stage stone clearance rate.

Objective:To retrospectively analyze and summarize the clinical experience and therapeutic effect of anterograde Needle-perc combined with RIRS, namely N+ R (Needle perc + RIRS) technique in the treatment of complex calyceal diverticular stone.Methods:Retrospective analysis of 23 cases of complex renal caliceal diverticulum stones admitted to our hospital from January 2020 to December 2022. The complex factors mainly include the invisible cervical orifice of diverticulum, large stone volume, and special anatomical location, which makes single RIRS or PCNL treatment difficult or unsuccessful. There were 14 males and 9 females with an average age of (42.3±6.1) years. Three cases were upper calyceal diverticular stone, average size was (0.9±0.2)cm. Nine patients had diverticular stone in the middle posterior calyx, and the average size was (1.2±0.3)cm. The average size of four diverticular stone was (1.8±0.2)cm in the anterior middle calyx. Seven patients had diverticular stone with an average size of (1.3±0.1)cm in lower calyx. Among them, 12 patients underwent RIRS which were difficult or stone undiscovered, and 3 patients underwent PCNL and the operation was terminated due to failure of channel establishment. In our center, oblique supine lithotomy position (male) or prone split-leg position (female) was adopted, and the combined treatment of Needle-perc and RIRS was performed. Needle-perc puncture was completed under the guidance of full ultrasound. During the operation, methylene blue reagent or mutual guidance of two endoscopes was used to find the diverticulum neck and expand the outlet with holmium laser incision. Depending on the size and location of the stones, a single Needle-perc laser lithotripsy combined with stone removal in flexible ureteroscope was used, or dual lasers were be used simultaneously for stone removal under double endoscopes. The first stage stone free rate, operation time, hemoglobin decrease, complications, postoperative hospital stay and other conditions were analyzed.Results:All the 23 operations were completed successfully. The stone free rate within 48 hours and one month after surgery was 78.2% and 100.0% respectively. The average operation time was (61.5±12.2)min. The mean postoperative hospital stay was (2.8±0.6) days. The mean decrease of hemoglobin was (3.6±0.4)g/L. Three patients had fever and one patient had renal subcapsular effusion. After anti-inflammatory and symptomatic treatment, the patient was discharged. There was no incidence of Clavien-Dindo≥Ⅱcomplications such as blood transfusion, abdominal organ injury or urosepsis.Conclusions:Treatment of complex renal caliceal diverticulum stones using N+ R technique of anterograde needle-perc combined with RIRS can effectively improve the success rate of first-stage surgery. Overall, it is safe, efficient and feasible with the advantages of high stone free rate, lower damage, and few postoperative complications.

Objective:To analyze the reinfection rates in people previously infected with SARS-CoV-2 in Zhengzhou and Yuzhou cities (first infected with Delta/B.1.617.2 variant), and Anyang city (first infected with Omicron/BA.1.1 variant) in January 2022 and the population characteristics, and compare the differences in antibody levels among different populations.Methods:Serum samples were collected from 371 previously infected, 134 reinfected and 19 uninfected people for IgG antibody detection. Among them, serum samples from 45 previously infected, 44 reinfected and 19 uninfected people were tested with different novel coronavirus variants (early original strain, BA.5.2 variant, XBB.1.5 variant) for neutralizing antibody detection.Results:The rate of reinfection was 32.82% (85/259) in Zhengzhou and Yuzhou cities, and 19.92% (49/246) in Anyang city. The IgG antibody level in reinfected people was higher than that in previously infected and uninfected people ( P<0.05). The IgG antibody level in uninfected group was higher in people vaccinated within three months than in those vaccinated six months ago ( P<0.05). The IgG antibody level in the group receiving four doses of vaccine was higher than that in the group receiving three doses of vaccine ( P<0.05). The results of true virus neutralization antibody detection showed that in the Zhengzhou and Yuzhou cases, the level of neutralization antibody against the early original strain was higher than those against the BA.5.2 variant and the XBB.1.5 variant ( P<0.05), and the level of neutralizing antibody against BA.5.2 variant was higher than that against XBB.1.5 variant ( P<0.05). In Anyang city cases, the level of neutralizing antibody against the early original strain was higher than those against BA.5.2 variant and XBB.1.5 variant ( P<0.05); in the reinfected population, the level of neutralizing antibody against the early original strain was higher than that against the XBB.1.5 variant ( P<0.05). In addition, the levels of all neutralizing antibodies in both previously infected and reinfected people were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody in the infected population in Zhengzhou and Yuzhou cities was higher than that in the infected population in Anyang city and in uninfected population ( P<0.05). The levels of antibodies against BA.5.2 and anti-XBB.1.5 variants in infected people in Zhengzhou and Yuzhou cities were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody against BA.5.2 variants in the previously infected population in Anyang city was higher than that in the uninfected population ( P<0.05), and the level of neutralizing antibody against XBB.1.5 variants in the infected population in Anyang city was higher than that in the uninfected population ( P<0.05). Conclusions:After infection with SARS-CoV-2, the neutralizing antibodies produced in the human body have a certain cross-protection effect on other variants, but the antibody level will gradually decrease over time. Protection from a previous early SARS-CoV-2 variants infection against the current main circulating Omicron variants (such as XBB variants) is low, and the immunity conferred by pervious infection or booster vaccination may not be able to provide sufficient protection against new variants.

Objective:To understand the effects of paliperidone palmitate (PP) long-acting injection on hospitalization, psychiatric symptoms, individual and social function of community patients with schizophrenia.Methods:From March 2021 to September 2022, 239 patients with schizophrenia in the community of Zhongshan city were treated with PP injection in a 1-month dosage form for 1 year.The hospitalization rate was compared before and after the treatment.The brief psychiatric rating scale (BPRS), modified overt aggression scales(MOAS), clinical global impressions-severity(CGI-S), and personal and social performance scale (PSP) were used to evaluate psychiatric symptoms and personal social function at baseline, at the end of the 8th week, the end of the 6th month and the end of the 12th month after treatment.Repeated measurement analysis of variance was used to compare the results at different times of treatment, and Logistic regression analysis was used to analyze the factors affecting treatment by SPSS 26.0.Results:One year after treatment the number of hospitalization was lower than that before (0(1) times, 0(0) times)( Z=-4.43, P<0.01), and the hospitalization days was lower than before (43(83.3) days, 0(0) days)( Z=-8.65, P<0.01) for the schizophrenic patients.The total BPRS score for schizophrenic patients decreased from (45.3±9.2) to (27.5±9.0) after 1 year of treatment( χ2=465.20, P<0.01), and the external aggressive behavior score was lower than the baseline score (1(7), 0(0))( F=308.36, P<0.01). The total effective rates were 30.5%(73/239), 77.4%(185/239) and 81.6%(195/239) after 8 weeks, 6 months and 1 year of treatment, respectively.The impairment in the four aspects of personal and social functioning were improved to varying degrees (all P<0.01). The severity of the disease was reduced 1 year after treatment.And the proportions of partial to very severe, moderate, none or mild were 10.0%(24/239), 56.5%(135/239), and 33.5%(80/239). Ordinal logistic regression analysis showed that younger age at treatment ( β=-0.08, OR=0.93, 95% CI=0.87-0.99) and older age at first onset ( β=0.07, OR=1.07, 95% CI=1.01-1.14) were associated with better treatment outcomes. Conclusion:Long-term injection of paliperidone palmitate can effectively improve the mental symptoms and individual social function of community patients with schizophrenia.

Objective:To investigate the efficacy and safety of modified Bikini approach periacetabular osteotomy in the treatment of developmental hip dysplasia under 50 years of age.Methods:The clinical data of 39 patients with developmental hip dysplasia who underwent periacetabular osteotomy in the Department of Orthopedics, Guizhou Provincial People′s Hospital from June 2016 to June 2021 were retrospectively analyzed.Among them, 20 patients (21 hips) underwent the improved Bikini approach (study group) and 19 patients (20 hips) underwent the improved Smith-Petersen approach (control group).In the study group, there were 3 males and 17 females, aged( M(IQR))27.5 (14.3) years (range:11 to 44 years).In the control group, there were 2 males and 17 females, aged 27.5 (19.3) years (range:17 to 47 years).Both groups were sutured in the same manner by the same physician.Incision length, operation time, intraoperative blood loss and complications were recorded.X-ray images, anterior central marginal angle (ACE), lateral central marginal Angle (LCE) and acetabulum tilt angle (Tonnis AI) were measured before and after the operation.The coverage rate of acetabulum to femoral head (AHI) was measured and calculated, and the healing time was observed.Harris Hip score, International Hip score (IHOT)-12 and visual analogue scale (VAS) were recorded before and after surgery.Vancouver Scar Scale (VSS) score and patient and observer scar assessment scale (POSAS) score were recorded 12 months after surgery.The independent sample t test,Wilcoxon rank sum test, χ2 test or Fisher exact test was used to compare the clinical efficacy between the two groups, respectively. Results:All patients successfully completed the operation.There was no significant difference in operation time and intraoperative blood loss between the two groups (all P>0.05).The incision length of the study group was smaller than that of the control group, and the difference was statistically significant (10.5(5.0)cm vs.15.0(3.0), W=309.000, P=0.007).Patients were followed up for (19.1±11.1) months (range:12 to 60 months).Femoral nerve stretching injury occurred in 2 cases and sciatic branch fracture occurred in 1 case in the study group, all of which recovered to normal at 3 months follow-up, while no corresponding injury occurred in the control group.Lateral femoral cutaneous nerve injury occurred in 3 cases in the study group and 2 cases in the control group.Delayed wound healing occurred in 1 case in each of the two groups, and both healed after re-operation debridement and suture.Pubic branch nonunion occurred in 4 patients in the study group and 5 patients in the control group.There were no serious complications such as sciatic nerve and femoral blood vessel injury between the 2 groups, and there was no statistical significance in the incidence of complications between the 2 groups (52.4%(11/21) vs.40.0%(8/20), χ2=0.631, P=0.427).The clinical healing time of the patient was (4.5±1.3) months after surgery (range:3.0 to 8.0 months).There were no significant differences in ACE, LCE, Tonnis AI and AHI between the 2 groups (all P>0.05).At the last follow-up, there were no significant differences in VAS,Harris hip score and IHOT-12 score between the two groups (all P>0.05).The incision scars in the study group were smaller than those in the control group, and the differences in VSS and POSAS were statistically significant (all P<0.05). Conclusion:Compared with the improved Smith-Petersen approach, the improved Bikini approach has the same early clinical efficacy in the treatment of patients with developmental hip dysplasia under the age of 50, and has the advantages of smaller postoperative incision scars, more hidden and beautiful incision, and no serious complications, which is worthy of further study and promotion.

Objective:To investigate the efficacy and safety of modified Bikini approach periacetabular osteotomy in the treatment of developmental hip dysplasia under 50 years of age.Methods:The clinical data of 39 patients with developmental hip dysplasia who underwent periacetabular osteotomy in the Department of Orthopedics, Guizhou Provincial People′s Hospital from June 2016 to June 2021 were retrospectively analyzed.Among them, 20 patients (21 hips) underwent the improved Bikini approach (study group) and 19 patients (20 hips) underwent the improved Smith-Petersen approach (control group).In the study group, there were 3 males and 17 females, aged( M(IQR))27.5 (14.3) years (range:11 to 44 years).In the control group, there were 2 males and 17 females, aged 27.5 (19.3) years (range:17 to 47 years).Both groups were sutured in the same manner by the same physician.Incision length, operation time, intraoperative blood loss and complications were recorded.X-ray images, anterior central marginal angle (ACE), lateral central marginal Angle (LCE) and acetabulum tilt angle (Tonnis AI) were measured before and after the operation.The coverage rate of acetabulum to femoral head (AHI) was measured and calculated, and the healing time was observed.Harris Hip score, International Hip score (IHOT)-12 and visual analogue scale (VAS) were recorded before and after surgery.Vancouver Scar Scale (VSS) score and patient and observer scar assessment scale (POSAS) score were recorded 12 months after surgery.The independent sample t test,Wilcoxon rank sum test, χ2 test or Fisher exact test was used to compare the clinical efficacy between the two groups, respectively. Results:All patients successfully completed the operation.There was no significant difference in operation time and intraoperative blood loss between the two groups (all P>0.05).The incision length of the study group was smaller than that of the control group, and the difference was statistically significant (10.5(5.0)cm vs.15.0(3.0), W=309.000, P=0.007).Patients were followed up for (19.1±11.1) months (range:12 to 60 months).Femoral nerve stretching injury occurred in 2 cases and sciatic branch fracture occurred in 1 case in the study group, all of which recovered to normal at 3 months follow-up, while no corresponding injury occurred in the control group.Lateral femoral cutaneous nerve injury occurred in 3 cases in the study group and 2 cases in the control group.Delayed wound healing occurred in 1 case in each of the two groups, and both healed after re-operation debridement and suture.Pubic branch nonunion occurred in 4 patients in the study group and 5 patients in the control group.There were no serious complications such as sciatic nerve and femoral blood vessel injury between the 2 groups, and there was no statistical significance in the incidence of complications between the 2 groups (52.4%(11/21) vs.40.0%(8/20), χ2=0.631, P=0.427).The clinical healing time of the patient was (4.5±1.3) months after surgery (range:3.0 to 8.0 months).There were no significant differences in ACE, LCE, Tonnis AI and AHI between the 2 groups (all P>0.05).At the last follow-up, there were no significant differences in VAS,Harris hip score and IHOT-12 score between the two groups (all P>0.05).The incision scars in the study group were smaller than those in the control group, and the differences in VSS and POSAS were statistically significant (all P<0.05). Conclusion:Compared with the improved Smith-Petersen approach, the improved Bikini approach has the same early clinical efficacy in the treatment of patients with developmental hip dysplasia under the age of 50, and has the advantages of smaller postoperative incision scars, more hidden and beautiful incision, and no serious complications, which is worthy of further study and promotion.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

【Objective】 To observe the reactive change of cortical perivascular cells after craniocerebral injury and explore its mechanism. 【Methods】 The controllable cortical impact animal model was used to simulate craniocerebral injury, the expressions of cortical pericyte markers at different time points after trauma were studied by Western blotting, and the biological behavior of vascular pericytes after craniocerebral injury was determined by transmission electron microscopy. Post-traumatic high mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE), and nuclear factor κB (NF-κB) were detected by Western blotting. The experimental animals were divided into FPS-ZM1 (a specific RAGE receptor blocker) injection group and wild-type group. Wet and dry brain weight and transmission electron microscopy were used to study the post-traumatic effects of HMGB1-RAGE on pericytes. The primary mouse brain microvascular pericytes were cultured and supplemented with HMGB1 recombinant protein; the cultured pericytes supplemented with FPS-ZM1 were used as the control to explore the effect of HMGB1-RAGE pathway on vascular pericytes in vitro. 【Results】 The expression levels of early post-traumatic cortical pericyte markers platelet-derived growth factor receptor beta (PDGFR-β) and NG2 proteoglycan (NG2) decreased (PDGFR-β, Control vs. CCI 3D P<0.05; NG2, Control vs. CCI 6H P<0.05; Control vs. CCI 1D P<0.05). We found that pericytes were detached from blood vessels, accompanied by local blood-brain barrier opening. The expression of HMGB1-RAGE-NF-κB signaling pathway was increased in the early cortex after trauma (HMGB1, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05; RAGE, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05, Control vs. CCI 3D P<0.05, Control vs. CCI 5D P<0.05, Control vs. CCI 7D P<0.05; NF-κB, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05). After blocking the binding of RAGE with the ligand, cortical edema was reduced (CCI 6H P<0.05, CCI 1D P<0.05), and neurovascular unit damage was reduced. HMGB1 recombinant protein could increase the migration ability of cultured pericytes (Control vs. HMGB1 P<0.05, Control vs. HMGB1+FPS-ZM1 P<0.05), and could be reversed by FPS-ZM1 (HMGB1 vs. HMGB1+FPS-ZM1 P<0.05). 【Conclusion】 High-level HMGB1 after traumatic brain injury mediates pericytes’ detachment from blood vessels through RAGE on pericytes and leads to the occurrence of local cerebral edema.