Ankylosing spondylitis is a chronic immunoinflammatory disease that mainly affects the spine and the sacroiliac joint， the mechanism of which is closely related to signaling pathways， such as osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， phosphoinositide 3- kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）. Traditional Chinese medicine has the characteristics of multiple components and targets， and is widely used for the treatment of autoimmune diseases due to its low toxicity， strong specificity， and high efficacy. This review found that monomers and compounds of traditional Chinese medicine can exert anti ankylosing spondylitis effects by intervening in the aforementioned signaling pathways， regulating immune inflammatory responses， and inhibiting biological processes such as bone destruction， ectopic osteogenic differentiation， cell apoptosis， and autophagy.

Objective:To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. Methods:A child diagnosed with KS at the Fujian Children′s Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c. 6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported, and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:The c. 6285 dup variant of the KMT2D gene probably underlay the KS in this child.

Tumor heterogeneity is one of the characteristics of malignant tumors, which refers to the molecular biology or genetic changes in the daughter cells of tumors after multiple division and proliferation during the growth process, resulting in changes in tumor growth rate, invasion ability, drug sensitivity, and prognoses. Pituitary adenomas (PAs) are generally considered as benign tumors without obvious heterogeneity, but the identification of reliable heterogeneity markers still plays a key role in clinical diagnosis and treatment. In clinical practice, the heterogeneity of parenchymal PAs includes differences in imaging findings, histopathological findings, and molecular information. This article reviews the research results in PAs heterogeneity so as to provide better enlightenment for clinical research and practice.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To investigate the effects of microRNA(miR)-133b on epithelial-mesenchymal transition(EM)of human small airway epithelial cells induced by cigarette smoke extracts(CSE)and its regulatory mechanisms.Methods:The miR-expression profiles with microarray in airway epithelial cells of patients with chronic obstructive pulmonary disease were searched in the Gene Expression Omnibus(GEO)database, and the differentially expressed miRs were searched and verified by a real-time fluorescence quantitative method(qRT-PCR). Human small airway epithelial cells(HSAEpiC)were divided into the control group, the CSE group, the CSE+ miR-133b inhibitor transfection group(inhibitor group)and the CSE+ miR-133b inhibitor negative control transfection group(inhibitor control group)according to different intervention methods.Levels of miR-133b and mRNA levels of transforming growth factor(TGF)-β1, Smad2, E-cadherin and vimentin were detected by RT-PCR; Protein levels of E-cadherin and vimentin were detected by enzyme-linked immunosorbent assays(ELISA)and Western blotting.Results:Nine differentially expressed miRs were found in GSE53519, with miR-133b showing the most significant differential in thee HSAEpiC cell model after verification.CSE induced morphological changes in HSAEpiC cells, and miR-133b inhibitors could partially reverse the morphological changes in cell mode.mRNA and protein expressions of E-cadherin were decreased and expression of Vimentin mRNA and protein were increared in CSE induced HSAEpiC cells( F=9.09、12.35、7.57、101.87, P=0.015、0.007、0.023、0.000); miR-133b inhibitors partally reversed the mRNA and protein expressions of E-cadherin and Vimentin( F=40.59、27.74、15.87、20.42, P=0.000、0.001、0.004、0.002). CSE induced incresed expression of TGF-β1 mRNA and Smad mRNA in HSAEpiC cells, and miR-133b inhibitors partially reversed the changes in TGF-β1 mRNA and Smad mRNA( F=17.25、64.15, P=0.003、0.000). Conclusions:miR-133b may regulate CSE-related HSAEpiC cell EMT through the TGF-β1/Smad pathway.

Porcine deltacoronavirus (PDCoV) is a newly emerging enteropathogenic swine coronavirus causing acute diarrhea and vomiting in pigs. The apoptosis of ST cells induced by PDCoV infection was studied in this research. In ST cells, caspase activity assay showed that the activity of caspase 3, caspase 8 and caspase 9 increased significantly with the infection of PDCoV, but not observed in UV irradiated PDCoV-infected cells, indicating that PDCoV infection activated both endogenous and exogenous apoptotic pathways in ST cells, and the induction of apoptosis depended on viral replication. To further investigate the endogenous apoptosis induced by PDCoV, cytochrome C and apoptosis-inducing factors in cytoplasm and mitochondria were detected. Compared with normal cells, the amount of cytochrome C released from mitochondria to cytoplasm increased significantly in PDCoV-infected cells, and the release increased with the prolongation of infection, while the apoptosis-inducing factor was always localized to mitochondria, suggesting that PDCoV induced apoptosis was initiated through caspase-dependent mitochondrial apoptosis pathway by promoting cytochrome C in the mitochondrial membrane gap into the cytosol. In conclusion, this study reveals the mechanism of PDCoV inducing apoptosis.
Animals ; Apoptosis ; Coronavirus ; Coronavirus Infections ; Mitochondria ; Swine ; Swine Diseases

OBJECTIVETo explore the feasibility and clinical significance of precision low inferior mesenteric artery (IMA) ligation with the left colonic artery (LCA) preservation and root lymph node dissection in laparoscopic radical resection for rectal cancer, according to the inferior mesenteric artery (IMA) types.

METHODSOne Hundred and fore cases of rectal cancer patients who underwent laparoscopic resection in The Sixth Affiliated Hospital of Sun Yat-sen University from October 2015 to June 2016 were selected and divided into study group and control group according to different surgical methods. The study group (52 cases) accepted precision low IMA ligation with the LCA preservation and root lymph node (No.253) dissection, according to the IMA types and length examined by preoperative computed tomography angiography (CTA) reconstruction. The control group (52 cases) accepted the traditional high IMA ligation. The perioperative efficacy indexes and postoperative recovery situation of the two groups were compared.

RESULTSThe IMA types, IMA length and preoperative clinical stages were not significantly different between the two groups (all P>0.05). The surgery was completed smoothly for patients in both groups, with no conversion to open surgery. But two patients in the study group underwent left colonic artery ligation for intra-operative need. There were no significant differences in the operative time, intra-operative blood lose, the rate of protective ileostomy and post-operative pathological stages between the two groups (all P>0.05). More total lymph nodes [(24.9±5.7) vs. (16.9±4.2), P=0.001] and No.253 lymph nodes [(2.4±1.1) vs. (1.5±0.8), P=0.001] were harvested in study group as compared to control group. However, the positive rate of total harvested lymph nodes and No.253 lymph nodes between the two groups were not significantly different (P>0.05). There were no significant differences between the two groups in postoperative first anal exhaust time, postoperative hospital stay, total volume of postoperative intraperitoneal drainage, postoperative abdominal drainage tube retention time, postoperative anal drainage tube retention time and postoperative catheter retention time (All P>0.05). There were 2 cases of postoperative dysuria and 1 case of anastomotic bleeding in study group. There were 3 cases of postoperative dysuria and 2 cases of anastomotic leak in control group. Less postoperative complications (5.8% vs. 9.6%, P<0.05) in study group as compared to control group. There was no rehospitalization or death case in two groups within 30 days after operation.

CONCLUSIONSIn the laparoscopic radical resection of rectal cancer, preserving LCA and cleaning the root lymph nodes according to IMA types, which could increase the number of harvested lymph nodes and reduce the postoperative complications was safe and effective.

Objective To evaluate the prophylatic effect of recombinant human erythropoietin (rhEPO) on bronchopulmonary dysplasia (BPD) of preterm infants. Methods One hundred and fifty-five infants who were born at 26-29+6 weeks of gestation in Department of Neonatology, Guangdong Women and Children Hospital from January 1, 2009 to December 31, 2010 were randomly assigned to rhEPO-treated group (n=78) and control group (n=77) on admission. Randomization was stratified according to gestational age (26 or 27 weeks and 28 or 29 weeks). rhEPO-treated group was given the rhEPO at 300 U/kg, but none for the control group. Forty-eight hours after birth, rhEPO was injected subcutaneously every other day, three times a week for 4 weeks. The supportive care was same in the two groups. The outcomes at 36 weeks gestation included:(1) mortality of the infants;(2) incidence and severity of BPD;(3) rates of the complications, such as pneumonia, sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP) ; and (4) duration of oxygen and ventilation support. Mann-Whitney U, χ2, Fisher's exact or t test were used for statistical analysis. Results The incidence of BPD in rhEPO-treated group was lower than in the control group [18.6%(11/59) vs 36.8%(25/68),χ2=5.107,P=0.030), but there was no difference in the severity of BPD (P>0.05). There was no significant difference in the mortality rate between the two groups [12.8%(10/78)vs 7.8%(6/77), P>0.05]. The duration of the mechanical ventilation and oxygen therapy was shorter in rhEPO-treated group than in the control group [oxygen therapy:166.4(138.9-198.1) h vs 288.9(287.4-312.9)h, U=361.000;mechanical ventilation:80.5(67.7-95.1) h vs 150.4(148.9-151.9) h, U=88.000;both P<0.05]. There were no significant differences between the two groups in the rates of the complications, including pneumonia, sepsis, NEC, IVH, PDA and ROP, in preterm infants during hospitalization (all P>0.05). Conclusion Prophylatic treatment of rhEPO in preterm infants could decrease the incidence of BPD, and reduce the duration of the mechanical ventilation and oxygen therapy, but without increasing any side effects.

Objective To probe the causes,early recognition and effective therapy of posttraumatic biloma.Methods The data of all patients with the injury of the liver and bile duct treated in our center during the past 10 years were reviewed.Patients,diagnosed with biloma were retrospectively analyzed in respects of sex,age,cause of biloma,methods and efficacy of diagnosis and treatment.Results There were 46 patients with biloma.Of them,40 were found after liver trauma of grade Ⅲ-Ⅴ.The incidence of biloma was 15.2％ (40/263).In grade Ⅳ,Ⅴ,and Ⅲ,it was 22.6％ (31/137) and 7.1％ (9/126) respectively (x2 =12.20,P ＜ 0.01) and in blunt and penetrating injury,it was 19.3％ (35/181) and 6.1％ (5/82) respectively (x2 =7.67,P ＜ 0.01).Of these 40,36 were found during the course of conservative therapy of severe liver trauma; and 4 were found after laparotomy for the liver trauma.The remaining 6 cases of biloma had a history of injury to extrahepatic bile duct with a incidence of 18.8％(6/32).All 46 patients received spiral CT scaning plus MRI in 9,and ERCP in 11.Of those 40 with biloma after severe liver trauma,28 were cured by ultrasound-guided or computed tomography scan-guided pigtail drainage; and the remaining 12,in whom the biloma volume ＜ 30 cm3 resolved spontaneously.Six patients in whom the biloma as a result of injury to extrahepatic bile duct were cured by surgical intervention.There was no death and complication related with the therapy of biloma.Conclusions Attention should be given to biloma formation,when nonoperative therapy is exercised for severe liver trauma.Ultrasound-or CT scan-guided pigtail drainage is an effective option,but those due to injury of extrahepatic bile duct require surgical intervention.

Objective To explore the difference of the clinical manifestations between the elderly and non-elderly patients with non-massive pulmonary thromboembolism (PTE) and the significance of D-dimer in the diagnosis of PTE and its dynamic change after anticoagulant therapy.Methods The clinical manifestations of 83 cases with PTE were retrospectively analysed and divided into two groups:39 elderly and 44 non-elderly.The dynamic changing of D-dimer content was determined by immunoturbidimetry(ITM) method before and 3 d after anticoagulant therapy in the two groups.Results There were no significant statistical differences in the incidence of the main symptoms:dyspnea,cough,emptysis,syncope,palpitations between the elderly and the non-elderly (x2 =2.74,0.06,0.10,0.49,0.01,P＞0.05) except for the incidence of chest pain [14 cases (35.9 ％) vs.30 cases (68.2 ％),x2 =4.95,P ＜ 0.05].No differences were found in the the main signs:shortness of breath,tachycardia,accentuation or split of second pulmonary valve sound,cyanosis,and engorgement of neck veins between the two groups (x2 =2.60,0.03,0.61,0.06,0.33,0.11,P＞0.05).D-dimer content was lower in the elderly than in the non-elderly [(1.89±1.21) mg/L vs.(4.93±3.88) mg/L,Z=-2.55,P=0.01] before anticoagulant therapy.But there was no difference in D -dimer content between the two groups 3 d after anticoagulant therapy [( 1.28 ±1.11) mg/L vs.(2.09±2.22) mg/L,Z=-7.07,P=0.50].The decreasing level of D-dimer was less prominent in the elderly than in the non-elderly [(0.61±1.01) mg/Lvs.(2.84±2.95) mg/L,Z=-3.54,P=0.001].Conclusions The main clinical manifestations are similar between the elderly and non-elderly with non-massive PTE,but the incidence of chest pain is less in the elderly than in the non-elderly.The content of D-dimer is lower in the elderly than non-elderly after PTE and its decrements are less prominent in the elderly than the non-elderly after anticoagulant therapy.