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Based on the background of a multidisciplinary treatment team and the increasing high-quality life aspirations of patients,the preservation of anal function for patients with low rectal cancer has undergone changes in recent years.With the optimization of neoadjuvant therapy,refinement of surgical techniques,and the deepening of the concept of anal preservation after surgery,the concept of anal preservation for low rectal cancer has gradually shifted from traditional simple surgery to comprehensive treatment,and anal preservation surgery tends to be more accurate preservation.The goal of comprehensive treatment is to preserve good anal function and reduce surgical damage.However,comprehensive treatment for anal preservation in low rectal cancer is still in its infancy,and there is no consensus on the strategy planning for anal preservation.Therefore,summarizing various preoperative,intraoperative,and postoperative treatment strategies for low rectal cancer is of great significance for the selection of anal preservation schemes for patients with low rectal cancer.This article focus on exploring the optimization of neoadjuvant therapy models,"watch and wait"plans,the development of anal preservation techniques,and postoperative and preservation strategies,aiming to review the current status of anal preservation strategy planning for low rectal cancer.
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The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
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Humanos , Antivirales/química , COVID-19 , Tratamiento Farmacológico de COVID-19 , Ensayos Analíticos de Alto Rendimiento , Simulación del Acoplamiento Molecular , Inhibidores de Proteasas/química , SARS-CoV-2/enzimología , Proteínas no Estructurales ViralesRESUMEN
OBJECTIVE To explore the regulatory effects of baicalin on the proliferation and migration of human periodontal ligament stem cells (hPDLSCs) induced by lipopolysaccharide (LPS) and Janus protein tyrosine kinase 2 (JAK2)/signal transduction and transcription activator 3 (STAT3) signaling pathways. METHODS hPDLSCs were divided into control group, LPS group, different concentration baicalin groups (0.1, 1 and 10 mg/L). ELISA method and CCK-8 assay were used to determine the contents of cell inflammatory factors [interleukin 6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α)] and cell viability, so as to screen the optimal concentration of baicalin for follow-up pathway validation experiments. The cells were then divided into control group, LPS group, optimal baicalin concentration group and inhibitor group (10 μg/mL LPS+1 mg/L baicalin +3 μmol/L JAK2/STAT3 pathway inhibitor AG490). After treated for 24 h, the proliferation rate of hPDLSCs, apoptosis rate, migration rate, invasion cell number, mRNA and protein expressions of Cyclin D1 and caspase-3, the expression of JAK2/STAT3 pathway-related proteins were all detected. RESULTS According to cell inflammatory factors and cell viability, 1 mg/L was selected as the optimal concentration of baicalin. Compared with control group, cell proliferation rate, migration rate, invasion cell number, Cyclin D1 mRNA and protein expression were significantly decreased in LPS group, while cell apoptosis rate, caspase-3 mRNA and protein expression, p-JAK2 and p-STAT3 protein expression were significantly increased (P<0.05). After treated with 1 mg/L baicalin, the above indexes were reversed significantly (P<0.05). The improvement of above indexes in the inhibitor group was more obvious (P<0.05). CONCLUSIONS Baicalin can promote the proliferation, migration and invasion of LPS-induced hPDLSCs and inhibit their apoptosis and inflammation by blocking the JAK2/STAT3 pathway.
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Guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) are updated and revised based on the research advances in chronic hepatitis B virus infection in China and globally and the previous editions of the guidelines. This article introduces the updates in natural history and the noninvasive diagnosis and treatment of fibrosis. In particular, the guidelines further expand the indications for patients with chronic hepatitis B virus infection, clearly defines the selection of the population benefiting from interferon therapy, and strictly limits the standard of oral nucleos(t)ide analogues. Meanwhile, the guidelines also recommend more active treatment of patients with low-level viremia and children in the immune-tolerant phase. The new edition of the guidelines will provide an important basis for expanding the screening for hepatitis B virus infection, improving diagnostic rate, optimizing treatment regimens, and standardizing clinical management in China.
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Objectives:To explore the early clinical efficacies of unilateral decompression and bilateral decompression by one-hole split endoscope(OSE)technique for moderate-severe lumbar spinal stenosis(LSS)with unilateral symptoms amongst middle aged and elderly people.Methods:A retrospective analysis was performed on the patients with moderate-severe LSS who underwent unilateral decompression and bilateral decompression using OSE technique between January 2021 and December 2021.According to the inclusion and exclusion criteria,a total of 120 patients were enrolled in this study,with 60 patients in the unilateral decompression group(group A)and 60 patients in the bilateral decompression group(group B).The length of hospitalization,operative time,incision length and intraoperative blood loss were counted and compared between group A and group B.Moreover,range of motion(ROM)and sagittal translation(ST)on lumbar dynamic X-ray,facet preservation rate on the approach side,and cross-sectional area of the canal(CAC)of the surgical segment before and after operation were recorded and compared.The visual analogue scale(VAS)of back and leg pain was used before surgery,and at 7 days,3 months and 18 months after surgery,the Oswestry disability index(ODI)was used to evaluate the functional improvement,and the clinical efficacy was evaluated by modified Macnab criteria at the last follow-up.All the clinical scores of both groups were analyzed and compared between before and after surgery.Results:All the patients underwent surgical inter-vention successfully.There was no statistical significance in the length of hospitalization between groups A and B(P>0.05),but group B was longer in operative time,bigger in incision,and more in blood loss than group A,with statistical significance(P<0.05).The VAS for back and leg pain and the ODI after operation in both groups were all significantly lower than those before surgery,respectively(P<0.05),and the values at each postoperative time point within group were significantly different when compared pairwise(P<0.05);There was no significant difference between the two groups before surgery(P>0.05),but group B had more significant improvement than group A at 7 days,3 months and 18 months after surgery(P<0.05).There was no statistical significance in ST and ROM of surgical segment before and after surgery between the two groups(P>0.05).The postoperative facet preservation rate was higher in group B than in group A(P<0.05).There was no sig-nificant difference in the CAC of the surgery segment before operation between the two groups(P>0.05),how-ever,the CAC of the surgical segment in group B was larger than that in group A(P<0.05).The rate of im-provement in CAC was higher in group B than in group A(P<0.05).The CAC of the surgical segment postop-eratively in both groups were significantly larger than before surgery,with statistical significance(P<0.05).Ex-cellent-good rate at 18 months after surgery was 86.7%in group A and 91.7%in group B.There was no significant difference in the number of excellent and good cases between the two groups at 18 months after operation(P>0.05).One patient in group A had numbness and discomfort in the lower limb on the healthy side after surgery,and one case with mild dural tear in group B.Conclusions:Both unilateral decompression and bilateral decompression under OSE are safe and effective in the treatment of moderate and severe central canal and bilateral lateral recess stenosis with unilateral symptoms in the middle-aged and elderly people,with definite early clinical efficacy.Bilateral decompression is more complete and better in clinical efficacy than unilateral decompression,but further follow-up is required in the long term.
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OBJECTIVE@#To analyze the early effectiveness of unilateral biportal endoscopy (UBE) laminectomy in the treatment of two-level lumbar spinal stenosis (LSS).@*METHODS@#The clinical data of 98 patients with two-level LSS treated with UBE between September 2020 and December 2021 were retrospectively analyzed. There were 53 males and 45 females with an average age of 59.9 years (range, 32-79 years). Among them, there were 56 cases of mixed spinal stenosis, 23 cases of central spinal canal stenosis, and 19 cases of nerve root canal stenosis. The duration of symptoms was 1.5- 10 years, with an average of 5.4 years. The operative segments were L 2, 3 and L 3, 4 in 2 cases, L 3, 4 and L 4, 5 in 29 cases, L 4, 5 and L 5, S 1 in 67 cases. All patients had different degrees of low back pain, among of which 76 cases were with unilateral lower extremity symptoms and 22 cases were with bilateral lower extremity symptoms. There were 29 cases of bilateral decompression in both segments, 63 cases of unilateral decompression in both segments, and 6 cases of unilateral decompression and bilateral decompression of each segment. The operation time, intraoperative blood loss, total incision length, hospitalization stay, ambulation time, and related complications were recorded. Visual analogue scale (VAS) score was used to assess the low back and leg pain before operation and at 3 days, 3 months after operation, and at last follow-up. The Oswestry disability index (ODI) was used to evaluate the functional recovery of lumbar spine before operation and at 3 months and last follow-up after operation. Modified MacNab criteria was used to evaluate clinical outcomes at last follow-up. Imaging examinations were performed before and after operation to measure the preservation rate of articular process, modified Pfirrmann scale, disc height (DH), lumbar lordosis angle (LLA), and cross-sectional area of the canal (CAC), and the CAC improvement rate was calculated.@*RESULTS@#All patients underwent surgery successfully. The operation time was (106.7±25.1) minutes, the intraoperative blood loss was (67.7±14.2) mL, and the total incision length was (3.2±0.4) cm. The hospitalization stay was 8 (7, 9) days, and the ambulation time was 3 (3, 4) days. All the wounds healed by first intention. Dural tear occurred in 1 case during operation, and mild headache occurred in 1 case after operation. All patients were followed up 13-28 months with an average of 19.3 months, and there was no recurrence or reoperation during the follow-up. At last follow-up, the preservation rate of articular process was 84.7%±7.3%. The modified Pfirrmann scale and DH were significantly different from those before operation ( P<0.05), while the LLA was not significantly different from that before operation ( P=0.050). The CAC significantly improved ( P<0.05), and the CAC improvement rate was 108.1%±17.8%. The VAS scores of low back pain and leg pain and ODI at each time point after operation significantly improved when compared with those before operation, and the differences between each time points were significant ( P<0.05). According to the modified MacNab criteria, 63 cases were excellent, 25 cases were good, and 10 cases were fair, with an excellent and good rate of 89.8%.@*CONCLUSION@#UBE laminectomy is a safe and effective technique with little trauma and fast recovery for two-level LSS and the early effectiveness is satisfactory.
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Masculino , Femenino , Humanos , Persona de Mediana Edad , Laminectomía , Estenosis Espinal/cirugía , Constricción Patológica/cirugía , Dolor de la Región Lumbar , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Endoscopía , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Descompresión Quirúrgica , Herida Quirúrgica/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE@#To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology.@*METHODS@#20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×107/mice, n=20) and spleen nucleated cells (5×106/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5+ and Clu+ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings.@*RESULTS@#The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5+ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu+ cells were observed in the 5% group. The Lgr5+ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu+ cells in the 20% group significantly increased.@*CONCLUSION@#The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.
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Ratones , Femenino , Animales , Ratones Endogámicos C57BL , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped , Células Madre , OrganoidesRESUMEN
OBJECTIVE@#To observe the effect of electroacupuncture (EA) at different frequencies on learning and memory functions, as well as the relevant proteins of brain insulin signal transduction pathway in Alzheimer's disease (AD) mice and explore the effect mechanism of EA in treatment of AD.@*METHODS@#Seventy-two SPF Kunming male mice were randomized into a blank group, a sham-operation group, a model group, a 2 Hz EA group, a 15 Hz EA group and a 30 Hz EA group, 12 mice in each one. In the model group and each EA group, AD model were established by the injection with streptozotocin (ST2) solution (8 mg/kg) into the left lateral ventricles. In the sham-operation group, 0.9% sodium chloride solution of the same volume was injected into the left lateral ventricles. After successful modeling, in each EA group, EA was applied at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) with corresponding frequencies, once daily. One course of EA intervention consisted of 7 treatments and 2 courses were given totally at interval of 1 day. After modeling and intervention, Morris water maze test was conducted for the mice of each group. Using immunohistochemistry and Western blot method, the protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) was detected in the hippocampal of the mice after intervention.@*RESULTS@#Compared with the blank group, in the model group, the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) after modeling. When compared with the blank group, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) in the model group after intervention. In the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all shortened (P<0.01), and the number of crossing the platform was increased (P<0.05, P<0.01) after intervention when compared with the model group. The escape latency and the first time of crossing the platform were all shortened (P<0.01, P<0.05), and the number of crossing the platform was increased (P<0.05) in the 15 Hz and 30 Hz EA groups in comparison with the 2 Hz EA group. The protein expression levels of IR, IRS-1 and PI3K were reduced in the model group when compared with those of the blank group (P<0.01, P<0.05); and these protein expression levels were increased in the 15 Hz and 30 Hz EA groups compared with the model group (P<0.05, P<0.01). Compared with the 2 Hz EA group, the protein expression levels of IR, IRS-1 and PI3K were all elevated in the 15 Hz and 30 Hz EA groups (P<0.05).@*CONCLUSION@#The learning and memory function of AD mice may be improved through regulating brain insulin signaling transconduction pathway with electroacupuncture, and electroacupuncture at 15 Hz and 30 Hz obtains the overall better effect compared with the intervention at 2 Hz.
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Animales , Masculino , Ratones , Enfermedad de Alzheimer/terapia , Electroacupuntura , Hipocampo/metabolismo , Insulina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de SeñalRESUMEN
Objective:We conducted a real-world multi-center clinical study with a large sample size to comprehensively evaluate the performance of three commercial hepatitis C virus (HCV) core antigen assays. The study aimed to evaluate the performance for their use in HCV infection screening, and to provide clues for further improving the sensitivity and specificity of the assays.Methods:Key performance indicators including the lower limit of detection (LOD), diagnostic sensitivity, and specificity of three HCV antigen assays (the Architect, Laibo, and ChemClin HCV core antigen assays) were evaluated using commercial seroconversion panels reflecting early HCV infection and clinical routine serum samples of outpatients and inpatients from 3 tertiary hospitals from January 2018 to April 2022. Factors that affect the performance indicators were further investigated.Results:The window period for detecting HCV infection with the three antigen assays was equal to or slightly longer than that of the RNA assay, but all are shorter than that of the anti-HCV assay. There was a good linear positive correlation between HCV core antigen and HCV RNA levels in treatment naive patients with hepatitis C ( r=0.90, P<0.01). For the most common genotype 1b strain in China, the LOD of the three HCV assays were equivalent to 531 IU/ml (Architect), 3,698 IU/mL (Laibo), and 4,624 IU/mL (ChemClin) HCV RNA, respectively. Due to the skewed distribution of HCV RNA levels in treatment-naive hepatitis C patients, more than 95% of the patients had viral loads higher than 6 166 IU/ml. Therefore, the three HCV antigens assays still maintained a satisfactory diagnostic sensitivity (94.33%-99.40%). Among 54 immunodeficient patients (leukemia patients) with HCV infection, 9% (5/54) had negative anti-HCV results, while the HCV antigen assays found all these infectors. Through further experiments, we revealed the amino acid polymorphism in the core region of genotype 3 strain impaired the sensitivity of all three HCV antigen assays. In addition, the sensitivity of the two domestic assays was impaired by anti-HCV antibodies in the serum. The specificity of HCV antigen assays for diagnosing hepatitis C is 99.94% to 99.98%. The rheumatoid factors, autoantibodies, and other unknown interference substances can lead to a small number of low level, "false positive" antigen results. Conclusions:HCV core antigen assay may be used as a satisfactory approach of infection screening, especially for the immunodeficient patents. However, the sensitivity and specificity of the assays are influenced by multiple factors, which should be further improved.
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Objectives:To investigate the clinical value of a novel non-crosslinked biological mesh in laparoscopic inguinal hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 50 adult patients with unilateral inguinal hernia who were admitted to 3 medical centers, including Ruijin Hospital of Shanghai Jiaotong University School of Medicine et al, from September 2019 to March 2020 were selected. Based on random number table, patients were divided into two groups. Patients using the novel non-crosslinked biological mesh in repair surgery were divided into the experiment group and patients using the lightweight, micro-porous, partially absorbable synthetic mesh in repair surgery were divided into the control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) endpoint of the study. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter rank sum test. Count data were described as absolute numbers and (or) persentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Taking the recurrence rate of hernia as the basis of efficacy evaluation, according to the intention-to-treat analysis, the confidence interval method (Newcombe Wilson method) was used to conduct non-inferiority statistical analysis of the recurrence rate of hernia between the experiment group and the control group. If the upper limit of 95% confidence interval of the difference of recurrence rate of hernia between the experiment group and the control group is less than 10%, the experiment group is considered to be non-inferior to the control group. Results:(1) Grouping situations of the enrolled patients. A total of 50 adult patients with inguinal hernia were selected for eligibility. There were 44 males and 6 females, aged (60±15)years. All 50 patients were randomly divided into to the experiment group and the control group with 25 cases each. One patient in the control group was not followed up at postoperative month 2, and the rest of 49 patients completed all expected follow-up. No patient in the two groups fell off or were removed. (2) Endpoint of the study. ① The primary endpoint of study. The recurrence rate of hernia was 0 in the experiment group, versus 4%(1/25) in the control group, respectively, showing no significant difference between the two groups ( P>0.05). Results of non-inferiority statistical analysis showed that the 95% confidence interval of the difference of recurrence rate of hernia between the two groups was -19.54% to 9.72%, with the upper limit as 9.72%, which was less than 10%. ② The secondary endpoint of study. There were 2 patients in the control group occurred seroma at postoperative day 14, and none of the rest of patient in the two groups occurred seroma during the follow-up, showing no significant difference in the occurrence of seroma between the two groups ( P>0.05). There was 1 patient in the control group feeling discomfort or foreign body sensation in groin area at postoperative month 2, and none of the rest of patient in the two groups feeling discomfort or foreign body sensation in groin area during the follow-up, showing no significant difference in the feeling discomfort or foreign body sensation in groin area between the two groups ( P>0.05). There was no patient occurred surgical site infection in the experiment group, and there was 1 patient in the control group occurred postoperative skin infection, which had no relationship with mesh. There was no patient in both two groups occurred fever, anaphylaxis and patch related serious adverse reaction during the follow-up. The resting visual analogue scale score, active visual analogue scale score of patients at postoperative 2 days and postoperative 18 months were 0.44±1.00, 1.28±1.46 and 0, 0 in the experiment group, versus 0.40±0.76, 1.28±1.14 and 0.24±1.20, 0.44±1.29 in the control group, respectively. There was a significant difference in the time effect of postoperative active visual analogue scale score of patients between the two groups ( Ftime=10.19, P<0.05). The thickness of the novel non-crosslinked biological mesh before implantation was 0.5?0.7 mm. Two months after operation, results of B-ultrasonic examination in groin area of 10 patients from the experiment group showed a strong echo area at the patch implant area with a thickness as 2 mm. Conclusion:Application of novel non-crosslinked biological mesh in laparoscopic inguinal hernia repair is safe and effective.
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For patients with chronic hepatitis B, the indications of antiviral treatment are gradually expanding, and the pursuit of various degrees of cure (partial cure, functional cure and complete cure) is consistently improving, which enhances the urgent clinical need for improving the detection sensitivity of hepatitis B virus (HBV) surface antigen and DNA. Based on the availability of commercial highly sensitive hepatitis B surface antigen and HBV DNA detection reagents, we summarized their applications in the diagnosis of HBV infection, their role on guiding selection of antiviral treatment agents and treatment plans, their prediction efficacy and indication for drug withdrawal, their role on monitoring therapy efficacy and the prediction of disease outcomes. Taken together, highly sensitive hepatitis B virus surface antigen and DNA assays and related detection technology play an important role in the whole management process of chronic HBV infection.
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Objective To systematically review the epidemiological studies on primary biliary cholangitis (PBC), and to investigate the prevalence rate of PBC in the Chinese general population and its influencing factors. Methods PubMed, Embase, The Cochrane Library, CNKI, and Wanfang Data were searched for articles on the epidemiology of PBC in China published up to 31th March 2022. Two researchers independently performed screening and data extraction, and then related analyses were performed. Results A total of 9 articles were included. The positive rate of AMA was 1 049.05/100 000 (ranging fr om 159.65/100 000 to 2287.40/100 000), and the prevalence rate of PBC was 123.68/100 000 (ranging from 42.70/100 000 to 276.59/100 000). The positive rate of AMA was 636.51/100 000 (ranging from 52.55/100 000 to 1 164.33/100 000) in men and 1 265.47/100 000 (ranging from 225.23/100 000 to 1 704.93/100 000) in women, with a male/female ratio of 1∶1.99 for the prevalence rate of AMA. The prevalence rate of PBC was 40.81/100 000 (ranging from 23.54/100 000 to 75.10/100 000) in men and 148.71/100 000 (ranging from 77.36/100 000 to 214.91/100 000) in women, with a male/female ratio of 1∶3.64 for the prevalence rate of PBC. Conclusion Different studies show great differences in the positive rate of AMA and the prevalence rate of PBC in the Chinese general population, which is mainly affected by sex, age, and region. The positive rate of AMA and the prevalence rate of PBC increase with age, and the patients aged ≥50 years have a significantly higher positive rate of AMA than those aged < 50 years. The positive rate of AMA is significantly higher than the prevalence rate of PBC. There are significantly more women than men in the AMA-positive population and the PBC patients, and the influence of sex on AMA is lower than that on PBC.
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The extent of D3 lymphadenectomy for right colon cancer, especially the medial border of central lymph node dissection remains controversial. D3 lymphadenectomy and complete mesocolon excision (CME) are two standard procedures for locally advanced right colon carcinoma. D3 lymphadenectomy determines the medial border according to the distribution of the lymph nodes. The mainstream medial border should be the left side of superior mesenteric vein (SMV) according to the definition of D3, but there are also some reports that regards the left side of superior mesenteric artery (SMA) as the medial border. In contrast, the CME procedure emphasizes the beginning of the colonic mesentery and the left side of SMA should be considered as the medial border. Combined with the anatomical basis, oncological efficacy and technical feasibility of D3 lymph node dissection, we think that it is safe and feasible to take the left side of SMA as the medial boundary of D3 lymph node dissection. This procedure not only takes into account the integrity of mesangial and regional lymph node dissection, but also dissects more distant lymph nodes at risk of metastasis. It has its anatomical basis and potential oncological advantages. However, at present, this technical concept is still in the exploratory stage in practice, and the related clinical evidence is not sufficient.
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Humanos , Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Mesocolon/cirugíaRESUMEN
In recent years, human beings are constantly facing the threat of emerging infectious diseases. Forensic technology plays a unique role in responding to the emergencies and new epidemics. In epidemic prevention and control, forensic partitioners can provide important clues for the identification of vector animal species and the traceability of pathogen regions based on non-human DNA testing technology. In epidemic-related judicial practice, forensic partitioners bear more and more evidence responsibilities in dealing with biosafety laws-related issues, such as improper handling of epidemics and vaccine safety issues, which require forensic evidence. In terms of pathogen tracing, forensic physical evidence examinations identify species and individuals through biological materials extracted from the scene of death and autopsy of infectious diseases, are expected to provide informative clues for epidemiological investigations and point out the direction for pathogen tracing. In addition, forensic pathological examination can provide an important pathophysiological basis for determining the cause of death and the mechanism of death through autopsy, also offer necessary scientific evidence for clarifying the epidemiological characteristics of the epidemic and predicting the development trend of the epidemic.
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Animales , Humanos , Urgencias Médicas , Medicina Legal , Autopsia , Examen Físico , ADNRESUMEN
The succession of microbiota is closely associated with several essential factors, including race, sex, health condition, lifestyle, postmortem interval, etc., and it has great potential application value in forensic medicine. This paper summarizes recent studies on the forensic applications of the microbiome, including individual identification, geographical feature identification, origin identification of the tissue or body fluid, and postmortem interval estimation, and introduces the current machine learning algorithms for microbiology research based on next-generation sequencing data. In addition, the current problems facing forensic microbiomics such as the extraction and preservation of samples, construction of standardization and database, ethical review and practical applicability are discussed. Future multi-omics studies are expected to explore micro ecosystems from a comprehensive and dynamic perspective, to promote the development of forensic microbiomics application.
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Humanos , Medicina Legal , Autopsia , Microbiota/genética , Algoritmos , Secuenciación de Nucleótidos de Alto Rendimiento , Cambios Post MortemRESUMEN
OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.
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Animales , Ratones , Autofagia , Calcio/metabolismo , Condrocitos , Retículo Endoplásmico/metabolismo , Endorribonucleasas/farmacología , Homeostasis , Inositol , Ratones Noqueados , Proteínas Serina-Treonina Quinasas , ARN Mensajero/metabolismo , Sirolimus/farmacología , Tunicamicina/farmacologíaRESUMEN
Stimulator of interferon genes(STING)is a key protein in cGAS-STING signaling pathway and plays an important role in immune response mediated by the exogenous or endogenous DNA.This review describes the biological function of STING, the process of cGAS-STING pathway, the classification and administration of STING agonists, and summarizes the currently reported drug delivery systems.The delivery of STING agonists through appropriate drug carriers can overcome the lack of difficult entry, easy enzymatic hydrolysis, short half-life and poor targeting, improve the body's innate and adaptive immunity, and enhance the therapeutic effect of drugs.In conclusion, this paper mainly reviews the research progress of drug delivery system for STING agonists to provide basis for the development of drug delivery system and promote the clinical transformation and application of STING agonists.
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Objective To study the anatomical structure of normal and scoliotic thoracic vertebrae in adolescents aged 12-15 years in Northern Shanxi Province, to provide detailed information for pedicle screw placement, and to provide data references for screw size design. Methods Totally 120 cases of normal thoracolumbar CT of 120 adolescents aged 12 to 15 years and 30 cases of adolescent idiopathic scoliosis were collected in Northern Shaanxi Province. The raw data of thoracolumbar tomographic images scanned continuously were imported into Mimics16. 0 software for analysis and measurement in DICOM format. Measurement indicators: pedicle width, pedicle height, pedicle length, transverse diameter of spinal canal, longitudinal diameter of spinal canal, transverse pedicle angle,maximum transverse pedicle angle, sagittal pedicle angle and pedicle area. Results Pedicle width:12-13 years old, T
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Objective:To explore the effects of Tiaoren Tongdu Acupuncture on motor function and corticospinal tract (CST) remodeling after cerebral infarction. Methods:From February, 2017 to December, 2020, 54 patients with cerebral infarction were randomly divided into control group (n = 27) and acupuncture group (n = 27), each group was divided into subgroups 1, 2 and 3 according to the impairment of corticospinal tract, with nine cases for each subgroup. All the patients received routine medicine, while the acupuncture group received Tiaoren Tongdu Acupuncture, for four weeks. They were assessed with Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI) before and after treatment, and scanned with diffusion tensor imaging and diffusion tensor tractography, to obtain the fractional anisotropy (FA) and the bilateral FA ratio (rFA). Results:The scores of FMA and MBI, and FA and rFA increased in both groups (t > 2.841, P < 0.05) after treatment, and increased more in the acupuncture group than in the control group (t > 2.140, P < 0.05). Conclusion:Tiaoren Tongdu Acupuncture can promote the recovery of CST to improve motor function for patients with cerebral infarction.
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Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of <2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of <2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.