Mitochondrial diabetes mellitus(MDM)is a type of diabetes caused by mitochondrial gene mutations resulting in progressive secretory function defects of pancreatic islet β cells.MDM is a rare single-gene genetic disease,accounting for about 1%of all diabetes mellitus.We reported a case of MDM patient and their family.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Diabetic kidney disease(DKD)is one of the commonest microvascular complications of type 2 diabetes mellitus(T2DM).Inflammatory cytokines play an important role during the pathogenesis and development of DKD.This article reviews the research progresses on the role of inflammatory cytokines in DKD.

Objective:To examine the occurrence of complications in elderly patients who have undergone radical surgery for colorectal cancer.Additionally, this study aims to identify the various risk factors associated with these complications.Methods:This study included elderly patients with colorectal cancer who underwent radical surgery at Beijing Hospital between January 2013 and December 2020.These patients were divided into two groups based on their age.In this study, we examined a total of 906 patients who underwent surgery, with 695 patients under the age of 80 and 211 patients aged 80 and above.We classified postoperative complications into two categories: medical and surgical complications.Our analysis compared comorbidities, clinicopathological factors, perioperative variables, and postoperative morbidity and mortality between the two age groups.We utilized both univariate and multivariate analyses to identify any potential risk factors for postoperative morbidity.Results:When comparing patients under 80 years old to those aged 80 or older, it was found that the latter group had a lower body mass index, worse ASA scores, and more comorbidities.Additionally, the proportion of elderly patients with right colon cancer, pT3-4, and pN+ disease was higher compared to those under 80 years old.Furthermore, the elderly patients aged 80 or older had a lower rate of laparoscopic surgery compared to those under 80 years old.The study found that elderly patients aged 80 years and older had significantly shorter operation times compared to those younger than 80 years[(191.0±70.6)min vs.(214.0±83.3)min, t=3.642, P<0.001]. However, the overall complication rate was higher in the elderly group(32.7%)than in the younger group(22.6%)( χ2=8.839, P=0.004). Upon further analysis, it was found that medical complications increased significantly(20.9% vs.7.5%, χ2=30.547, P<0.001), whereas the rate of surgical complications did not show any statistical difference(15.6% vs.16.4%, χ2=0.069, P=0.832). The mortality rate during the perioperative period was found to be significantly higher in elderly patients aged 80 years and above compared to those below 80 years(1.9% vs.0.3%, χ2=6.316, P=0.029). Further analysis revealed that age was an independent risk factor for medical complications( HR=2.822, 95% CI: 1.804-4.414, P<0.001). Laparoscopic surgery has been shown to significantly decrease surgical complications( HR=0.475, 95% CI: 0.317-0.711, P=0.001). However, if the operation time exceeds 200 minutes, there is a significant increase in surgical complications( HR=1.942, 95% CI: 1.278-2.888, P=0.002). Conclusions:The incidence of postoperative medical complications in very elderly patients with colorectal cancer who undergo radical surgery has risen, although the rate of surgical complications has remained steady.Radical surgery for elderly patients with colorectal cancer is both safe and feasible, but it is important to prioritize the prevention and management of medical complications.

Objective: Investigate osteogenic differentiation of canine periodontal ligament stem cells ( cPDLSCs) via over-expression ephrinB2 in cPDLSCs． Methods : cPDLSCs were isolated from the premolars and molars of Beagle．After transfected with EfnB2-GFP-Bsd and GFP-Bsd empty Vector，cPDLSCs were induced to osteogenic differentiation．Western blot was used to invest the expression of ephrinB2 protein．The effect of osteogenic differentiation of EfnB2-cPDLSCs and Vector-cPDLSCs were analyzed by RT-PCR , CCK-8，Alizarin-red S staining and ALP. Results: There was no significant difference in cell proliferation between EfnB2-cPDLSCs and Vector-cPDLSCs．While EfnB2-cPDLSCs displayed an enhanced ALP activity and more prominent mineralized nodules compared with Vector-cPDLSCs．The odonto-/ osteogenic genes in EfnB2-cPDLSCs were also highly enhanced． Conclusion The results of our study indicated that ephrinB2 gene-transfected cPDLSCs showed enhanced osteogenic differentiation.

Objective:To investigate the surgical treatment of mesh infection after lapa-roscopic inguinal hernia repair.Methods:The retrospective and descriptive study was conducted. The clinical data of 32 patients with mesh infection after laparoscopic inguinal hernia repair who were admitted to the Affiliated Beijing Chaoyang Hospital of Capital Medical University from January 2018 to December 2020 were collected. There were 30 males and 2 females, aged 59(range, 19-81)years. All patients underwent debridement. Observation indicators: (1) surgical and postopera-tive situations; (2) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between was conducted using Fisher exact probability. Results:(1) Surgical and postoperative situations. All 32 patients underwent debridement success-fully, with the operation time and volume of intraoperative blood loss as 110(range, 45-220)minutes and 24(range, 5-200)mL. Of the 32 patients, there were 6 cases undergoing open debridement, 26 cases undergoing laparoscopic exploration with 12 cases clarified the cause of infection, in which 4 cases had intestinal fistula by mesh infection breaking through the peritoneum and invading the intestinal tract and underwent laparoscopic intestinal fistula repair, 3 cases had significant amount of residual medical glue, 3 cases had mesh wrinkling and curling, 2 cases underwent peritoneum suturing with black silk thread. There were 18 cases undergoing complete removal of infected mesh and 14 cases undergoing partial mesh removal. There were 18 cases undergoing removal of infected mesh by laparoscopic posterior approach and 14 cases undergoing removal of infected mesh by open anterior approach. Twenty-nine of the 32 patients had bacterial culture and drug allergy testing, including 24 cases with positive cultures, while 5 cases with negative cultures. The duration of hospital stay of the 32 patients was 27.0(range, 9.0-85.0)days. (2) Follow-up. All 32 patients were followed up for 37.9(range, 18.7-52.5)months. There were 5 cases and 2 cases with postoperative incision infection in the 18 patients undergoing complete removal of infected mesh and 14 cases undergoing partial mesh removal, respectively, showing no significant difference between them ( P>0.05). There were 7 cases, 4 cases with seroma, recurrent sinus in the 18 patients undergoing complete removal of infected mesh and 5 cases, 6 cases in the 14 cases undergoing partial mesh removal, respectively, showing no significant difference between them ( P>0.05). None of patient in the two groups had hematoma, recurrent inguinal hernia or chronic pain. The 7 patients with incision infec-tion recovered effectively after symptomatic treatment. The 12 patients with seroma received no special treatment. The 10 patients with recurrent sinus underwent debridement, in which 9 cases did not experience any further abdominal wall infections and 1 case underwent the third debride-ment. Conclusion:The management of mesh infection following laparoscopic inguinal hernia repair necessitates the expertise of hernia specialists to complete remove the infected mesh or partial remove the infected mesh based on the specific clinical scenario.

Objective:To investigate the short-term and long-term efficacy of laparoscopic surgery for colorectal cancer in elderly patients aged 80 and over.Methods:This study included patients aged 80 and over with sigmoid or rectal cancer who had undergone radical surgery in Beijing Hospital between January 2013 and December 2020.Of the enrolled patients, 47 underwent laparoscopic surgery, and 44 received open surgery.After 1∶1 propensity score matching(PSM), there were 32 cases in each group.Patient clinicopathological characteristics, surgery data, post-operative outcomes and long-term survival were compared.Results:Before PSM, there were significant differences in sex composition and tumor locations between the open surgery and laparoscopic surgery groups.After PSM, there was no significant difference in clinicopathological characteristics between the two groups.Before and after PSM, the operative time for laparoscopic surgery was statistically longer than that for open surgery.The intraoperative blood loss, the postoperative complication rate and the number of harvested lymph nodes were not significantly different between the two groups before and after PSM.Before and after PSM, the postoperative hospital stay in the laparoscopic operation group was shorter than that in the open surgery group, but the difference was not statistically significant.Before PSM, the 1-year, 3-year and 5-year survival rates of the open surgery group were 92.4%, 69.5% and 58.1%, respectively, and the 1-year, 3-year and 5-year survival rates of laparoscopic group were 91.3%, 79.8% and 69.5%, respectively.There was no significant difference in overall survival between the two groups before PSM( χ2=0.591, P=0.422). After PSM, the 1-year, 3-year and 5-year survival rates in the open surgery group were 89.3%, 67.1% and 52.2%, respectively, and the 1-year, 3-year and 5-year survival rates in the laparoscopic surgery group were 90.6%, 74.3% and 65.0%, respectively.There was no significant difference in the overall survival between the two groups after PSM( χ2=1.316, P=0.251). Conclusions:For elderly colorectal cancer patients aged 80 and over, laparoscopic surgery and open surgery have similar rates of complications and long-term survival.This study provides evidence for the safety of laparoscopic surgery.Further prospective randomized controlled clinical trials are needed to confirm these findings.

Objective : To investigate the effect of motile cilia of ependymal cells on cerebral edema induced by ischemic stroke. Methods : SD rats(n = 60) were randomly divided into sham group and ischemia⁃reperfusion model group. In the model group , a 2 h reperfusion 24 h model of ischemia was constructed by the method of suture. The Longa ′s⁃5 point method and the 2 , 3 , 5 ⁃triphenyltetrazolium chloride (TTC) staining were used to assess neurological function and the cerebral infarction volume , respectively. The dry and wet weight method was used to measure brain water content. The morphological changes of motile cilia were observed by HE staining and scanning electron microscope (SEM) . The level of SPAG6 expressed in tissues with motile cilia was measured by Western blot. Immunofluorescence was used to detect the structure of motile cilia and the expression distribution of SPAG6 in brain. Results : Compared with the sham group , the infarct volume and neurological function score of the model group increased significantly , and the brain edema was obvious (P < 0. 05) . HE staining and SEM results showed that the brain tissue structure of the sham group was tight and regular and the ependymal cell nucleus was round and full. The motile cilia in sham group were arranged orderly and the structure was complete. The brain tissue structure of the model group was loose and the ependymal cell nucleus was wrinkled、condensed and dyed. A large number of necrotic cells were generated , and the structure of motile cilia was disordered. The number and density of motile cilia were significantly reduced , and the arrangement was disordered. Western blot results showed that the total protein content of SPAG6 in the model group was higher than that in the sham group , but the results were not statistically different. Immunofluorescence results showed that compared with the sham group , the length of motile cilia in the model group was significantly shorter (P < 0. 05) . The fluorescence intensity of SPAG6 in the model group was higher than that in the sham group , but the results were not statistically different. Compared with the sham group , the average fluorescence intensity of SPAG6 in ependymal cells of the model group significantly increased , and the difference was statistically significant (P < 0. 05) ; and cerebral ischemia⁃reperfusion injury reduced the expression of SPAG6 fluorescence in the cilia ( P < 0. 05 ) . Conclusion Cerebral ischemia⁃reperfusion down⁃regulates the expression of SPAG6 in motile cilia of ependymal cells , resulting in abnormal structure and dysfunction of motile cilia , and subsequent brain edema injury.

Objective:To analyze the characteristics of eyes with congenital optic disc pits (ODPs) through multimodal imaging.Methods:A cross-sectional study was conducted.Thirty-eight patients (38 eyes) diagnosed with congenital ODPs in the Second Hospital of Hebei Medical University from January 2009 to January 2020 were enrolled.A comprehensive summary analysis of the imaging results including fundus photography, spectral domain-optical coherence tomography (SD-OCT), infrared imaging, fundus autofluorescence (FAF), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) was performed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Second Hospital of Hebei Medical University (No.2021-P011). Written informed consent was obtained from each subject prior to any medical examination.Results:Among the 38 eyes, there were 32 eyes with ODPs located in or below the temporal side of optic disc, 4 eyes with ODPs located above the temporal side of optic disc, and 2 eyes with ODPs located at the center of optic disc, which were round or quasi-circular pale depression, and dark red eminences with clear or unclear boundaries between milk spots were found in 29 eyes with optical-disc macular degeneration (ODP-M) by fundus photography.SD-OCT examination showed that the structure of lamina cribrosa in the lesion area in all ODPs patients was incomplete, which presented a dark area with no tissue reflection, and the fissure led to the deep optic nerve.Fluid was found in the outer nuclear layer in all ODP-M patients, and there were 27 eyes with fluid in the inner nuclear layer, 13 eyes in the ganglion cell layer, and 4 eyes under the inner limiting membrane.Among the 29 eyes with ODP-M, there were 21 eyes with retinoschisis in outer layer, 27 eyes with neuroepithelial detachment.In the 27 eyes with neuroepithelial detachment, spot-like high reflection and reduced or disappeared ellipsoid band reflectance were seen above the neuroepithelium in 18 eyes.In infrared images, there were circular or quasi-circular low-reflection areas in the temporal side of the optic disc, and the lesion of ODP-M eyes presented low-reflection areas.FAF examination showed that in 27 eyes with ODP-M, there was a hypofluorescent region at the posterior pole consistent with the lesion range, among which, there was a granular or sheet-like hyperfluorescence at the center of the hypofluorescent region in 18 eyes.FFA showed that the optic disc depression in the arterial phase of patients was in a localized hypofluorescence state.During the venous phase, fluorescein dye extravasation along the temporal side of the optic disc could be found.A strong fluorescent arc with unclear boundaries at the temporal edge of the optic disc was formed in the late stage of angiography.Among the 29 eyes with ODP-M, the area of the macular lesion showed hyperfluorescence during the late stage of angiography in 27 eyes with neuroepithelial detachment, and no extension of dye toward the macula was found.ICGA showed that the optic disc depression of ODPs patients presented a localized hypofluorescence, and the lesion showed hyperfluorescence in 27 of the 29 ODP-M eyes with neuroepithelial detachment.Conclusions:Multimodal imaging can be helpful to realize the early diagnosis, etiology analysis of ODPs and make treatment plan.