Objective To investigate the renoprotective effects of autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) in diabetic rats. Methods Sprague-Dawley (SD) rats were injected intraperitoneally with 40 mg/kg streptozotocin (STZ) for 5 consecutive days to induce type 1 diabetes. Four weeks following STZ injection, eighteen SD rats were randomized into two groups: the diabetic group (n = 9) and the ADMSCs group (n = 9). Normal nondiaetic rats were set as the normal control (n = 9). Autologous ADMSCs were cultured and identified in vitro , which were intravenously injection to the ADMSCs group rats via the tail vein. At 8 weeks after transplantation, levels of blood glucose, insulin, serum urea nitrogen, serumcreatinine and urine protein were measured. Meanwhile the body weight and kidney weight were examined. Results Mesenchymal cell surface markers were expressed in the cultured ADMSCs. The ADMSCs could differentiate into the adipogenic and osteoblastic lineages. Both the diabetic group and the ADMSCs group rats had higher levels of blood glucose , urea nitrogen , serum creatinine , urine protein and higher ratio of the kidney weight/body weight than those in the normal control group (P < 0.05, respectively). Blood glucose, urea nitrogen and the ratio of kidney weight/body weight in the ADMSCs group rats were significantly decreased compared with the diabetic group (P < 0.05, respectively). The decreased insulin level was attenuated after transplantation of ADMSCs (P < 0.05). Besides, levels of serum creatinine and urine protein in the ADMSCs group were lower than those in the diabetic group with no significant difference. Conclusion Autologous transplantation of ADMSCs can improve metabolic disorder and relieves diabetic renal damage.

ObjectiveTo summarize the experience of diagnosis and different surgical management for Nevin Stage V gallbladder cancer. Methods The present study was an retrospective analysis of 74 patients who were operated in our hospital and suffered from Nevin Stage V gallbladder cancer proved histopathologically. ResultsThe diagnostic accuracy of color Doppla ultrasound was 75.0%(21/28), abdominal enhanced CT, 82.1%(32/39).23 patients with Nevin Stage V disease received radical or extended radical cholecystectomy, the mean survival time was 1 year and 3 months;11 patients with Nevin Stage V disease without a complete resection had a mean survival of 6 months; 38 patients with Nevin Stage V diesase had a mean survival of 2 months after palliative bypass procedure or biopsy. ConclusionA exploratory operation by laparoscope is useful in the diagnosis of advanced gallbladder cancer. According to local situation of gallbladder cancer and general body state, different management are employed in treatment so that the effect may be improved.

Objective To analyze the risk factors and the prognosis in patients with cerebral venous sinus thrombosis(CVST)accompanied by early-onset seizures.Methods A retrospective study was conducted on 163 patients with CVST admitted to the Department of Neurology and Neurosurgery of Shengjing Hospital of China Medical University during August 2011 to November 2022 as the study subjects.Based on whether they had concurrent seizures within 14 days after diagnosis CVST,the patients were divided into the early-onset seizures group(42 cases)and the non-early-onset seizure group(121 cases).Clinical data were collected,including general clinical data,imaging data,laboratory test results,and treatment plans,etc.The general clinical data involves gender,age,suspected etiology(infection[such as mastoiditis,otitis media,sinusitis,etc.],oral contraceptives/estrogen,pregnancy/puerperium,anemia and other factors that can lead to changes in blood composition,hyperhomocysteinemia),clinical manifestations(including headache,dizziness,disturbance of consciousness,nausea and vomiting,limb numbness,hemiplegia,tinnitus,aphasia,diplopia,mental abnormalities,unresponsiveness,isolated intracranial hypertension[papilledema],etc.).Imaging data includes involved venous sinus location,multiple venous sinuses(involving ≥ 2 venous sinuses)and intracranial changes(intracranial hemorrhage,venous cerebral infarction,subarachnoid hemorrhage).All patients were tested for D-dimer on the second day of admission.Patients with intracranial hypertension were examined with spinal puncture and measured cerebrospinal fluid pressure,with elevated cerebrospinal fluid pressure defined as the pressure＞180mmH2O.The patients were followed up by telephone 2 months after discharge,and the modified Rankin scale(mRS)was used to assess the prognosis of the patients(mRS score ≤2 points as good prognosis,mRS score＞2 points as poor prognosis).The mortality rate of patients was measured.The clinical data,imaging data,laboratory test results,treatment and follow-up results of the two groups were compared.The correlation variables with P＜0.05 in the univariate analysis were included in the multivariate Logistic regression model to analyze the independent risk factors of CVST accompanied by early-onset seizures.Results(1)Compared with the non-early-onset seizure group,the proportion of pregnant/puerperal females in the early-onset seizure group was higher(33.3％vs.13.2％,P=0.004),the proportion of patients with hemiplegia was higher(23.8％vs.6.6％,P=0.005),and the proportion of patients with CVST imaging combined with intracranial hemorrhage was higher(40.5％vs.13.2％,P＜0.01),with all the differences were statistically significant.There was no significant difference in other baseline clinical data between the two groups(all P＞0.05).(2)Further multivariate Logistic regression analysis showed that pregnancy/puerperium(OR,4.854,95％CI 1.917-12.290,P=0.001),hemiplegia(OR,3.871,95％CI 1.246-12.028,P=0.019)and intracranial hemorrhage(OR,5.005,95％CI 2.038-12.288,P＜0.01)were independent risk factors for CVST with early-onset seizures.(3)There were 3 patients(7.1％)in the early-onset seizure group and 6 patients(5.0％)in the non-early-onset seizure group dead,and there was no significant difference in the proportion of death between the two groups(P=0.887).The proportion of patients with good prognosis in the early-onset seizure group was lower than that in the non-early-onset epilepsy group(81.0％vs.92.6％),and the difference between the groups was statistically significant(P=0.043).Among the patients treated with anticoagulation alone,the good prognosis rate of non-early-onset seizures group(99/106,93.4％)was higher than that of the early-onset seizure group(32/40,80.0％),and the difference was statistically significant(P=0.029).Conclusions For CVST patients,especially females during pregnancy or postpartum period,clinical manifestations accompanied by hemiplegia,and with intracranial hemorrhage on imaging,the risk of seizures within 14 days of the diagnosis of CVST should be vigilant.The prognosis of CVST patients with early-onset seizures is worse than that of patients without early-onset seizures.

Cathepsins,the most abundant hydrolases in lysosomes,are responsible for the degradation of various substrates.Increasing evidence suggests that cathepsins play important roles in neurodegenerative diseases.Cathepsins affect the progression of diseases by regu-lating the aggregation of abnormal proteins(e.g.α-synuclein,amyloid β-protein,huntington).Abnormal expression levels and activity and gene mutations of cathepsin B,D,and L in the nervous system can lead to the occurrence and development of neurodegenerative diseases.This review summarizes the research progress on cathepsins in neurodegenerative diseases in recent years,with a view to providing a basis for the early diagnosis and treatment of these diseases.

Objective To analyze the genetic characteristics of VP1-VP4 genes carried by cox-sackievirus A6 (CVA6) strains isolated from severe cases of hand, foot, and mouth disease (HFMD) in Shenzhen during 2012 to 2015. -ethods The VP1-VP4 genes of CVA6 strains isolated from severe HFMD cases in Shenzhen during 2012 to 2015 were amplified and sequenced. Phylogenetic analysis was performed to analyze the VP1-VP4 genes of CVA6 isolates and sequences downloaded from GenBank by using DNASTAR6. 0 and MEGA6. 02 software packages. Results Four cases of severe HFMD were caused by CVA6 in Shenzhen during 2012 to 2015. All of the patients had the symptom of fever, skin rash and aseptic encephalitis. The CVA6 strain causing severe HFMD in 2013 shared 98. 8％-98. 9％ homology in nucleotide sequences and 99. 3％-99. 8％ in amino acid sequences with the strains isolated in 2012. Two amino acid mutations were found in the CVA6 strain isolated in 2013, which were G73E in VP2 region and S13G in VP1 region. However, the CVA6 strain isolated in 2015 only shared 95. 0％ homology in nucleotide sequences and 99. 3％ homology in amino acid sequences with the strain isolated in 2013. Six amino acid mutations were identified including E73G in VP2 region and T5A, S27N, A30V, N137S and V242I in VP1 region. The phylogenetic analysis revealed that the four CVA6 strains belong to D3 sub-genotype. The CVA6 strains causing severe cases in 2012 had the nearest genetic relationship with the strain isolated in Changsha in 2012 (KJ156349). The CVA6 strain isolated in Shenzhen in 2013 had the nearest genetic relationship with the strain isolated in Shanghai in 2013 (KJ612513). The Shenzhen CVA6 isolate in 2015 showed high similarity to Weifang CVA6 isolate in 2014 (KX752785). Conclusions All CVA6 strains causing severe HFMD ca-ses in Shenzhen during 2012 to 2015 belongs to D3 sub-genotype. Mutations of S27N and A30V in the VP1 region of the CVA6 isolate in 2015 are located in the B cell epitopes. In addition, the VP1-V242I mutation in the CVA6 strain isolated in 2015 is located in the binding site of PSGL-1 receptor. These mutations may affect the binding of CVA6 strains to the cellular receptors and their infectivity to people.

The gross specimens and tissue slices used for traditional experimental pathology curriculum are fragile, and some specimens or slices are difficult to be supplemented. Besides, the classroom and schedule for experimental pathology teaching are inflexible. Therefore, the teaching effects for experimental pathology course are limited. The development of digital technology has promoted the teaching reform of medical experimental curriculum. We have digitalized the gross specimens and tissue slices to preserve and expand the samples, and constructed pathological sample repository containing both physical samples and digital samples. Furthermore, we have established a platform for remote access, and thus improved the flexibility and autonomy of study for experimental pathology curriculum. Additionally, we have integrated clinical information of the teaching samples, and interpreted the specimens with the assistance of two-dimensional code technology and voice broadcast technology, to realize human-computer interactive learning. The questionnaire shows that the application of pathological sample repository in experimental teaching has improved student learning effect and recognition.

Objective: To investigate the genetic characteristics of VP1 genes carried by coxsackievirus A16 strains isolated from cases of hand foot and mouth disease (HFMD) in Shenzhen during 2016 to 2017. Methods: Fecal and anal swab specimens were collected from patients with mild HFMD in four sentinel hospitals and the Institute of Pathogen Biology, Shenzhen Center for Disease Control and Prevention, China during 2016 to 2017. All specimens were tested for CVA16 viral RNA using real-time RT-PCR. The VP1 genes of 51 randomly selected CVA16 strains were amplified by RT-PCR and then sequenced using TaKaRa Biomedical Technology (Dalian). Bioinformatics software, including Mega6.02, BioEdit and DNAStar, was used for comparison and analysis of the VP1 genes. Results: CVA16 strains in Shenzhen during 2016 to 2017 mainly belonged to B1a and B1b subtypes as well as an emerging subtype B3. The epidemic of B1b subtype was found in both 2016 (28 strains) and 2017 (19 strains), while the B1a subtype (two strains) was only detected in 2017. Two B3 subtype strains were detected in 2017. The strains of B1b subtype were closely related to the strains isolated in Shanghai (JQ314149), Wenzhou (KP289416) and Beijing (KU254598), while the B1a subtype strains were closely related to the strains isolated in Kunming (JQ316639) and Tailand (GQ184139). The B3 subtype strain was an emerging CVA16 epidemic strain in mainland China. Further comparison of the CVA16 epidemic strains in Shenzhen area during 2016 to 2017 with the CVA16 strains causing severe neurological symptoms showed that two amino acid mutations (S14N and M23L) were found in VP1 protein. Conclusions The epidemic strains of CVA16 were B1b subtype in Shenzhen area in 2016. However, B1a, B1b and the emerging B3 subtype strains were prevalent in 2017. Compared with the CVA16 strains causing severe neurological symptoms, the CVA16 strains circulating in Shenzhen during 2016 to 2017 carried two amino acid mutations inVP1 protein.

To meet the requirement of pathological practice and development, we systematically analyzed the situation of pathological residents training and the importance of initiating the clinical scientific research training. Additionally, we proposed the principle and implementation strategy for clinical scientific research training. According to features of pathological practice, we employed the modularized teaching to divide the training courses into several modules: discussion module for clinical pathology, lecture module for advanced research, and training modules for basic scientific theory, technology and writing skill. With these approaches, the systematic and structured system of standardized residents training is implemented to improve the clinical research ability of pathological residents.

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.