BACKGROUND:Most scholars now believe that children with cerebral palsy who have severe spinal deformities in early childhood(<15 years of age)may have a higher risk of progression of spinal deformities,which may result from imbalances in movement due to pelvic tilt,pain,etc. OBJECTIVE:To investigate the relationship between lumbar spine development and hip joint development in children with spastic cerebral palsy. METHODS:A retrospective analysis was performed in 102 children with spastic cerebral palsy admitted at Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from January 2014 to December 2021.All admitted children had X-rays of the pelvic position and the lumbar lateral position.Anteroposterior X-ray of the pelvis was performed to measure femoral head migration percentage,central edge angle,neck-shaft angle,and acetabular index.The sagittal Cobb angle,sacral slope,arch-top distance,and lumbar lordosis index were measured by the lateral X-ray of the lumbar spine.Correlation of the two sets of indicators was further analyzed.All children were divided into normal group,risk group,hip subluxation group and total hip dislocation group according to their femoral head migration percentage,and the differences in lumbar spine indexes between groups were evaluated. RESULTS AND CONCLUSION:Pearson correlation analysis showed that the femoral head migration percentage was moderately positively correlated with sagittal Cobb angle and arch-top distance,and weakly positively correlated with lumbar lordosis index;the central edge angle was moderately negatively correlated with the arch-top distance and weakly negatively correlated with the sagittal Cobb angle;the neck-shaft angle was weakly positively correlated or not correlated with the sagittal Cobb angle and lumbar lordosis index;and the acetabular index was weakly positively correlated with the sagittal Cobb angle and arch-top distance.No statistically significant correlation was found between the remaining indicators.According to the femoral head migration percentage,the children were divided into four groups,including 25 cases in the normal group,41 cases in the risk group,27 cases in the hip subluxation group,and 9 cases in the total hip dislocation group.The sagittal Cobb angle was significantly increased in the risk group,the hip subluxation group and the total hip dislocation group compared with the normal group,showing an increasing trend group by group,and there were significant differences between groups(P<0.05).Compared with the normal group,the lumbar lordosis index in the risk group and the hip subluxation group increased significantly,and there were significant differences between groups(P<0.05).There was an increase trend in the lumbar lordosis index of the total hip dislocation group compared with the normal group.Compared with the normal group,the arch-top distance in the hip subluxation group and the total hip dislocation group increased significantly(P<0.05),and there was a stepwise increasing trend.There was no significant difference in sacral slope between groups.To conclude,the development of the lumbar spine in children with cerebral palsy is closely related to the development of the pelvic hip joint,and the most obvious relationship is between lumbar lordosis and hip dislocation.

Objective To explore the clinical features and treatments of Chinese patients with bullous pemphigoid (BP) induced by immune checkpoint inhibitors (ICI). Methods A retrospective analysis was conducted on 18 Chinese patients with ICI-induced BP treated in the Peking Union Medical College Hospital and 14 Chinese patients with this disease reported in the literature.Furthermore,the research data of non-Chinese patients were used for comparison to outline the clinical features and treatment responses of the Chinese patients. Results A total of 32 patients (21 males and 11 females) were enrolled,and all of them presented BP induced by programmed death-1/programmed death ligand-1 inhibitors.Compared with non-Chinese patients,the Chinese patients with ICI-induced BP showed low average ages [(65.2±9.5) years vs. (69.9±10.3) years,P=0.020],increased proportion of BP induced by tislelizumab (28.1% vs. 0,P<0.001),decreased proportions of BP induced by pembrolizumab (18.8% vs. 39.4%,P=0.029) and nivolumab (3.1% vs. 52.8%,P<0.001),and decreased proportion of primary malignant melanoma (9.4% vs. 43.3%,P<0.001).The incidence of pruritus (96.9% vs. 66.1%,P<0.001) and mucosal involvement (59.4% vs. 15.7%,P<0.001) in the Chinese patients were higher than those in the non-Chinese patients.The proportions of the Chinese patients treated with tripterygium glycosides (9.4% vs. 0,P=0.008),dupilumab (18.8% vs. 0.8%,P<0.001),and topical corticosteroids (87.5% vs. 53.5%,P<0.001) were higher than those of non-Chinese patients. Conclusions The Chinese patients with ICI-induced BP tend to have a younger age and a higher probability of BP induced by tislelizumab than the non-Chinese patients.Unlike that in the non-Chinese patients,the primary tumor in the Chinese patients with ICI-induced BP is predominantly lung cancer.Pruritus is more obvious,and mucosal involvement is more common in the Chinese patients.Systemic corticosteroid therapy is the international standard treatment for ICI-induced BP,while tripterygium glycosides and dupilumab are characteristic therapies in China.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Antibodies, Monoclonal, Humanized/therapeutic use* ; East Asian People ; Immune Checkpoint Inhibitors/adverse effects* ; Pemphigoid, Bullous/chemically induced* ; Retrospective Studies

Objective To investigate the viability of Runt-related transcription factor 1(RUNX1)as a biomarker for gastric cancer and to assess the impact of the small molecule inhibitor Ro24-7429 on the proliferation,migration,and invasion of gastric cancer cells following targeted modulation.Methods Through the GEPIA database,we analyzed RUNX1 mRNA expression in gastric cancer or normal gastric tissues.Utilizing RUNX1 expression data from the TCGA database,a receiver operating characteristic(ROC)curve was constructed to appraise the potential of RUNX1 as a gastric cancer biomarker.In September 2022,we collected tissue samples from 6 patients with gastric cancer from the Department of General Surgery at the Second Hospital of Lanzhou University.After extracting tissue proteins,Western blotting was employed to compare RUNX1 protein expression in tumor and adjacent tissues.Gastric cancer cell lines with high RUNX1 expression were identified and the suppressive effect of the small molecule inhibitor Ro24-7429 on RUNX1 protein expression was verified by Western blotting.the effect of Ro24-7429 was validated by using CCK-8,colony formation,cell scratch,and Transwell assays.RUNX1 protein levels in gastric cancer tissues were quantified using immunohistochemical staining.An organoid model of gastric cancer was then established from the high-expression samples and verified by both HE and immunization analyses.Lastly,the impact of Ro24-7429 on the growth of gastric cancer organoids with meticulous tracking was evaluated using a biological microscope within a designated area.Results The analysis from the GEPIA database revealed a heightened expression of RUNX1 mRNA in gastric cancer tissues compared with normal tissues(P<0.05).The ROC curve derived from the RUNX1 expression data in the TCGA database boasts an area under the curve(AUC)of 0.956,underscoring RUNX1's potential as a robust diagnostic marker.Western blotting results revealed significantly higher RUNX1 protein expression in gastric cancer tissues than in adjacent tissues(P<0.001).Among 5 gastric cancer cell lines studied,AGS and HGC27 exhibited pronounced RUNX1 protein expression(P<0.001).The small molecule inhibitor Ro24-7429,targeting RUNX1,potently suppressed RUNX1 expression in gastric cancer cells.The results from CCK-8,colony formation,scratch,and Transwell assays showed that Ro24-7429 effectively inhibited proliferation,migration,and invasion of gastric cancer cells(P<0.001).In a gastric cancer organoid model derived from high RUNX1 expression samples,the RUNX1 expression was remarkably consistent with its originating tissue.As expected,upon the targeted inhibition of RUNX1 using Ro24-7429,the cancer organoids significantly reduced growth capacity.Conclusions RUNX1 shows potential as a biomarker for gastric cancer.Ro24-7429 specifically inhibits RUNX1 expression and suppresses tumor cell proliferation,migration,and invasion in gastric cancer cell lines and organoid models.

ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules（TBK） on type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats， which were then respectively treated （ig） with low-dose （0.625 g·kg^-1）， medium-dose （1.25 g·kg^-1）， and high-dose （2.5 g·kg^-1） TBK for 12 weeks. Fasting blood glucose （FBG） and body mass were recorded every 4 weeks during the treatment. One week before sampling， the feed intake of rats was detected， and after 12 h night fasting， oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was used to evaluate glucose tolerance， and the homeostatic model assessment for insulin resistance （HOMA-IR） was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes： Fasting serum insulin （FINS）， serum total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， and nonesterified fatty acids （NEFA）. The liver was weighed to calculate the liver index， and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. The protein levels of insulin receptor substrate （IRS）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt） and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group （P<0.01）， and the feed intake the administration groups was lower than that in the model group （P<0.05， P<0.01）. At the 8^th and 12^th week， the body mass in the model group was lower than that in the normal group （P<0.01）. Compared with the model group， TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group （P<0.01）. The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group， and AUC in the administration groups was significantly different from that in the model group （P<0.01）. The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group （P<0.01）， and they were lower in the TBK groups than in the model group （P<0.01）. Serum levels of TG， TC， HDL-C， NEFA （P<0.05， P<0.01）， and LDL-C were higher in the model group than in the normal group. Serum levels of TG， TC， LDL-C， and NEFA in the TBK groups were lower than those in the model group， and the levels of TG， LDL-C， and NEFA in TBK groups were concentration-dependent （lowest levels in high-dose TBK group）. Compared with the model group， high-dose TBK significantly increased the level of HDL-C （P<0.05）. Liver index of the model group was higher than that in the normal group （P<0.01）. The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver， the model group had unclear structure of liver lobule， enlarged cells of different sizes， and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury， particularly the high dose. For the PAS staining， compared with the normal group， the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein， p-IRS1/IRS1， and p-Akt/Akt in the model group were lower than those in the normal group （P<0.01）， and they were higher in the high-dose TBK group than in the model group （P<0.01）. ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.

ObjectiveTo explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ， ip） at 35 mg·kg^-1 for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg^-1）， medium-dose （1.25 g·kg^-1）， and high-dose （2.5 g·kg^-1） TBK groups， and lipoic acid group （0.026 8 g·kg^-1） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4^th， 8^th， and 12^th week of administration. At the 12^th week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （P<0.01）. The levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group （P<0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （P<0.01）. Compared with the model group， TBK of the three doses lowered the TWL （P<0.05， P<0.01） and the levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve of rats （P<0.05， P<0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （P<0.05， P<0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Two totiviruses, temporarily named Totivirus ND3 (TOV_ND3) and FD17 (TOV_FD17), were isolated from Culex tritaeniorhynchus captured in Shanghai City. The full sequences were determined using high-throughput sequencing method. The results showed that the genomes of TOV_ND3 and FD17 were 7612 and 7611 nucleotides, respectively in length, and encoded a capsid protein and an RNA-dependent RNA polymerase. The nucleotide sequence of TOV_ND3 had the highest similarity to Cx. tritaeniorhynchus totivirus NJ2, while the FD17 was most similar to Omono River virus strain AK4, with 84. 6％ and 84. 9％ identity, respectively, and 74. 1％ identity between themselves. Phylogenetic analysis revealed that the two newly obtained viruses were grouped into the unassigned totiviruses. Our results suggested that the two new viruses were variant totiviruses.

Objective To research the monoclonal antibody KMP1 inhibited bladder cancer EJ cell lines growth and metastasis in vivo by bioluminescence imaging. Methods Immunohistochemistry was used to determine the KMP1 binding to EJ and EJ-GFP cell lines. The xenograft tumor cell growth and distribution were measured by vernier calipers and dynamic in vivo fluorescence imaging. Immunohistochemistry and H&E counterstaining researched the feature of the xenograft tumor. Results Cell growth curves of EJ and EJ-GFP cells were similar. EJ-GFP had a green fluorescence. In EJ-GFP nude mouse tumor model, the addition of KMP1 significantly inhibited tumor growth and extended the average life span of nude mice. Both EJ and EJ-GFP cells can bind to KMP1,and the weight of transplanted tumors in the KMP1 treatment group was significantly lower than that of the mIgG control group (P＜0.001).Conclusion KMP1 has a promising antitumor effect in vivo. It might be valuable for development as a promising targeted agent for bladder cancer.

Objective To investigate the clinical value and the experience of retroperitoneal laparoscopic nephrectomy in primary hospitals. Methods A retrospective analysis of 20 cases of retroperitoneal nephrectomy performed in the people's hospital of Jianshui from July 2014 to December 2017 and 23 cases of open nephrectomy in the same period as the control group, the two groups of surgery and postoperative recovery were analyzed and compared. Results The two groups of patients were operated successfully. The surgery time of the laparoscopic group was (110.14 ±15.63) min and the control group was (100.33 ±10.58) min. There was no statistical difference between the two groups (P＞0.05). No complications occurred during the follow-up period between the two groups, and the difference was not statistically significant. The intraoperative blood loss in the two groups was (40.63 ±22.21) ml and (80.45 ±38.31) m L respectively, and the difference was statistically significant (P＜ 0.05).The indwelling time of drainage tube in the two groups was (2-3) days and (6-7) days respectively. The difference was statistically significant (P＜ 0.05), and the hospitalization time was (3.2 ±2.2) days and (6.4 ± 3.3) days respectively, the difference was statistically significant (P＜0.05). Conclusions Laparoscopic nephrectomy has the advantages of less trauma, faster recovery and shorter hospital stay. With the improvement of operation technique, it will bring more advantages and be worth popularizing.