Objective To study the effects of Guizhi Shaoyao Zhimu Decoction on factors related to bone destruction and bone protection in rats with collagen-induced arthritis(CIA)based on osteopro-tegerin(OPG)/receptor activator of NF-κB ligand(RANKL)/receptor activator of NF-κB(RANK)signaling pathway.Methods According to the body weight,60 female Wistar rats were randomly di-vided into the following six groups:the normal group,the model group,the Triperygium wilfordii mul-tiglucoside group(0.01 g/kg),the Guizhi Shaoyao Zhimu Decoction low-dose group(8.6 g/kg),the Guizhi Shaoyao Zhimu Decoction medium-dose group(17.2 g/kg),and the Guizhi Shaoyao Zhimu Decoction high-dose group(34.4 g/kg)(n=10 rats per group).The rats in all groups except for the normal group were given 100 μg bovine type Ⅱ collagen on the 1st and 8th days to establish the CIA model,and was injected into the left foot sole and tail root of the rats.After the successful modeling,the rats were treated by gavage for 4 weeks.The general state,body weight,and arthritis index(AI)score of rats were recorded,and the contents of RANKL and OPG in rat serum were determined by enzyme-linked immunosorbent assay.The mRNA and protein expressions of RANKL,RANK,and OPG in the ankle joint were determined through real-time PCR and Western blotting,respectively.Results Com-pared with the normal group,the general state of the model group was poor,the toe swelling was obvious,the AI score was increased,the serum RANKL content was increased,the serum OPG content was de-creased,and the mRNA and protein expressions of RANKL and RANK in the ankle joint were increased(P＜0.05).Compared with the model group,the degree of toe swelling and the AI score of rats in the Guizhi Shaoyao Zhimu Decoction low-,medium-,and high-dose groups were decreased,the serum RANKL content was decreased,the serum OPG content was increased,the mRNA and protein expres-sions of RANKL and RANK in the ankle joint were decreased,the mRNA and protein expressions of OPG were increased,and the RANKL/OPG ratio of the ankle joint was decreased(P＜0.05).Conclusion Guizhi Shaoyao Zhimu Decoction can improve the destruction of joint bone in CIA rats,and its mecha-nism of action may be related to reducing RANKL level,reducing RANKL/OPG ratio,and regulating bone balance.

Objective To study the effect of fine particulate matter(particulate matter 2.5,PM2.5)exposure on hepatic lymphangiogenesis in C57BL/6J mice and metabolic-associated fatty liver disease(MAFLD)model mice,and to provide a novel target for prevention and treatment of PM2.5-induced liver injury.Methods Forty male C57BL/6J mice were randomly divided into a control group,PM2.5 group,MAFLD group,and PM2.5-MAFLD group.Mice in the MAFLD and PM2.5-MAFLD groups were fed high-fat diet for 12 weeks,and mice in the other groups were fed normal chow diet.From weeks 13 to 16,mice in the PM2.5 and PM2.5-MAFLD groups were exposed to PM2.5 by tracheal instillation(twice per week),and mice in the other groups were instilled with saline at the same time.All animals were euthanized 24 h after the last PM2.5 instillation.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured,and the expression of LYVE1 in liver tissues was visualized using immunofluorescence staining.Hepatic oxidative stress markers levels(4-HNE and GSH/GSSG)were measured.The protein expression levels of lymphangiogenesis markers(PROX1 and LYVE1),lymphangiogenesis regulatory protein VEGF-C,and the lymphatic junctional function marker VE-cadherin in liver tissue were determined using Western Blot.Results PM2.5 exposure significantly increased the levels of serum AST and ALT,markedly decreased the protein expression of PROX1 and LYVE1,increased the protein expression of VEGF-C and VE-cadherin in the liver,increased the level of 4-HNE,and decreased the T-GSH/GSSG ratio in livers of mice in the MAFLD group(P＜0.05).However,PM2.5 exposure did not affect the levels of serum AST and ALT,protein expression of PROX1,LYVE1,or VEGF-C;level of 4-HNE;or T-GSH/GSSG ratio in the livers of the C57BL/6J mice(P＞0.05).Conclusions PM2.5 exposure obviously aggravated hepatic oxidative injury and reduced hepatic lymphangiogenesis by reducing the VEGF-C concentration in the livers of MAFLD model mice.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective To investigate the clinical feasibility,safety and advantages of transum-bilical laparoscopic single-site surgery in large hysterectomy.Methods A total of 82 patients with laparoscopic large hysterectomy were selected as the study objects.Among them,41 patients under-went transumbilical single-hole laparoscopic surgery(single-hole group)and 41 patients underwent traditional multi-hole laparoscopic surgery(multi-hole group).Operation time,intraoperative blood loss,24 h postoperative Visual Analogue Score(VAS),postoperative exhaust time,postoperative morbidity,postoperative hospital stay,cosmetic incision score,postoperative inflammatory index,neutrophil lymphocyte ratio(NLR),incidence of complications and the difference of hemoglobin be-fore and after surgery were compared between the two groups.Results The operation was successful-ly completed in both groups without conversion to laparotomy,and no serious surgical complications occurred.No auxiliary holes were added in the single-hole group.The postoperative exhaust time in the single-hole group was significantly shorter than that in the multi-hole group,the VAS score at 24 h after surgery and NLR at the first day after surgery were significantly lower than those in the multi-hole group,and the aesthetic score of the postoperative incision was significantly higher than that in the multi-hole group(P＜0.05).Conclusion Under the condition of strict control of surgi-cal indications,transumbilical laparoscopic single-site surgery in large hysterectomy has good safety and high feasibility,and has the advantages of fast postoperative exhaust,relieved postoperative pain,light immunosuppression and a incision.

Objective To investigate the clinical feasibility,safety and advantages of transum-bilical laparoscopic single-site surgery in large hysterectomy.Methods A total of 82 patients with laparoscopic large hysterectomy were selected as the study objects.Among them,41 patients under-went transumbilical single-hole laparoscopic surgery(single-hole group)and 41 patients underwent traditional multi-hole laparoscopic surgery(multi-hole group).Operation time,intraoperative blood loss,24 h postoperative Visual Analogue Score(VAS),postoperative exhaust time,postoperative morbidity,postoperative hospital stay,cosmetic incision score,postoperative inflammatory index,neutrophil lymphocyte ratio(NLR),incidence of complications and the difference of hemoglobin be-fore and after surgery were compared between the two groups.Results The operation was successful-ly completed in both groups without conversion to laparotomy,and no serious surgical complications occurred.No auxiliary holes were added in the single-hole group.The postoperative exhaust time in the single-hole group was significantly shorter than that in the multi-hole group,the VAS score at 24 h after surgery and NLR at the first day after surgery were significantly lower than those in the multi-hole group,and the aesthetic score of the postoperative incision was significantly higher than that in the multi-hole group(P＜0.05).Conclusion Under the condition of strict control of surgi-cal indications,transumbilical laparoscopic single-site surgery in large hysterectomy has good safety and high feasibility,and has the advantages of fast postoperative exhaust,relieved postoperative pain,light immunosuppression and a incision.

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.
Asthma ; Humans ; Inflammation ; Respiratory System ; Rhinitis, Allergic ; Sinusitis

Objective:To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome.Methods:The data of 3 children with febrile infection-related epilepsy syndrome admitted to the First Affiliated Hospital of Zhengzhou University from May to June 2019 were collected retrospectively, and their clinical characteristics, diagnosis, treatments and prognosis were summarized in combination with relevant literature.Results:The age of onset was 6-9 years old.The time interval from fever to first convulsion was 4-7 days, and they progressed to status epilepticus within 24 hours.The seizures were mainly multifocal seizures.Cerebrospinal fluid laboratory examination was normal.Electrocardiogram shows diffuse slow wave activity as the background, and epileptic waves dominated by the temporal area.Cranial magnetic resonance imaging showed signs of edema in 2 cases during the acute phase.All patients were resistant to multiple (4-5) anti-epileptic drugs, but high-dose anesthetic drugs can effectively terminate status epilepticus.All cases developed into refractory epilepsy, 2 cases had cognitive impairment and 1 case had movement impairment after 1 year.Conclusion:Febrile infection-related epilepsy syndrome often occurs in school-age children who have been physically healthy, which was included by fever.The seizures are explosive and refractory in febrile infection-related epilepsy syndrome, and it lacked specific laboratory indicators.High-dose anesthetics can effectively terminate status epilepticus, but it always has a poor prognosis.

Clinical data of a child with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) diagnosed in the First Affiliated Hospital of Zhengzhou University in June 2020 were retrospectively analyzed.A female patient with 1 year and 2 months old presented with 10 months of developmental delay and 1 month of recurrent seizures.Physical examinations showed grade Ⅲ muscle strength of limbs, slightly higher muscle tone, active reflex of bilateral knee tendons, normal reflex of bilateral achilles tendons, and positive Babinski sign.Brain magnetic resonance imaging (MRI) showed bilateral cerebral hemisphere atrophy and diffuse abnormal signals.The whole exome sequencing test showed two heterozygous mutations of the DARS2 gene in the present case.There are no reports of early-onset LBSL gene mutation in Chinese population.A total of 6 related foreign literatures have been reported.All affected cases present psychomotor development disorders and other encephalopathy manifestations.Brain MRI involvement and DARS2 gene mutations are found in previous reports.Therefore, for children with developmental retardation, epilepsy, and diffuse abnormal signals in both cerebral hemispheres examined by brain MRI, genetic testing is recommended to confirm the diagnosis, guide prenatal diagnosis and genetic counseling.

OBJECTIVE: To explore the genetic basis for 7 patients with Alström syndrome. METHODS: DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4). CONCLUSION ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.
Alstrom Syndrome/genetics* ; Cell Cycle Proteins/genetics* ; Humans ; Mutation ; Pedigree ; Whole Exome Sequencing

Retrospective analysis of the clinical data of a child with type 102 mental retardation caused by DDX3X gene mutation in the pediatric diagnosis of the First Affiliated Hospital of Zhengzhou University in April 2019.A 2 years and 3 months old girl with " delay for more than 1 year" , using second-generation sequencing technology for full exon detection, and the result is DDX3X gene 13 th exon c. 1463G>A hybridization mutation, this is a new mutation.There are no Chinese cases reported with DDX3X gene mutations, and there are 8 related cases were reported in foreign literature, all children have different degrees of intellectual disability.So patients with unexplained intellectual disability(especially female patients) need to be wary of the possibility of DDX3X gene mutation.