With the increasing recognition of myelin oligodendrocyte glycoprotein(MOG)antibody and N-methyl-D-aspartate receptor(NMDAR)antibody overlap syndrome(MNOS),the hypothesis on the mechanism of double antibody positivity has gradually been refined.It is believed that both antibodies can appear simultaneously or successively.When they appear successively,the disease spectra mediated by the two antibodies overlap,leading to the diversity of such disease syndromes and making clinical identification challenging.Initially,NMDAR-IgG often appears first,NMDAR encephalitis(NMDARE)is diagnosed primarily.Later,when the disease recurs or exhibits clinical features of MOG-IgG associated disorders,it suggests the coexistence of both antibodies.NMDARE patients with MOG-IgG positivity tend to have a younger age of onset,are more prone to recurrence,are more likely to have prodromal infection,are highly sensitive to hormones,and rarely have comorbidities with tumors,indicating a good prognosis.This may suggest a new disease entity.This article summarizes the current research progress on the pathophysiology and clinical features of MNOS.

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

OBJECTIVE: To investigate the effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the surgical efficacy of short-segment percutaneous pedicle screw fixation for thoracolumbar burst fractures with high rate of spinal canal encroachment. METHODS: From January 2016 to January 2022, 38 patients with thoracolumbar burst fractures with high rate of spinal canal encroachment (spinal canal encroachment rate >40%, complete posterior longitudinal ligament, no flipping bone block in the posterior marginal of the vertebra) without spinal cord injury who were were treated with short-segment percutaneous pedicle screw fixation were retrospectively analyzed. During the operation, 18 cases were used distraction-reduction first and then intermediate instrumentation on injured vertebral and sequential distraction-reduction again(the distraction-reduction first group) including 8 females and 10 males with a mean age of 46.5 (38.5, 50.0) years old, and the other 20 cases were used intermediate instrumentation on injured vertebral first and then direct distraction-reduction(the intermediate instrumentation first group) including 10 males and 10 females with a mean age of 46.0 (35.8, 50.8) years. The anterior height ratio of the injured vertebra, local Cobb's angle of the injured vertebrae, the spinal canal encroachment rate, and the improvement rate of spinal canal encroachment were compared and evaluated. RESULTS: All patients were followed up for more than 1 year, and no complications such as spinal cord and root injury, screw loosening and screw rod fracture were found. The anterior height ratio of the injured vertebra, local Cobb' angle of the injured vertebra in the two groups were significantly improved compared with preoperative data(P<0.05), and those at 3 months and 1 year after operation was lost compared with that at the previous time point(P<0.05). Although the spinal canal encroachment rate of the two groups 1 day and 1 year after operation was improved compared with that before operation(P<0.05), the improvement of spinal canal volume in the distraction-reduction first group was significantly better than that in the intermediate instrumentation first group (P<0.01). CONCLUSION In the treatment of patients with thoracolumbar fractures with high rate of spinal canal encroachment, short-segment percutaneous pedicle screw internal fixation with distraction-reduction first and then intermediate instrumentation and sequential distraction-reduction again can more effectively reduce the bony encroachment in the spinal canal and achieve indirect decompression effect better.
Humans ; Female ; Male ; Adult ; Middle Aged ; Spinal Fractures/surgery* ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Fracture Fixation, Internal/instrumentation* ; Pedicle Screws ; Retrospective Studies ; Spinal Canal/surgery*

BACKGROUND:Currently,there are various rat models of lumbar disc herniation used in experiments,each with its own advantages and disadvantages.The most common modeling methods include autologous nucleus pulposus transplantation and annulus fibrosus puncture models.OBJECTIVE:To establish two autologous nucleus pulposus transplantation models(with spinous process and mastoid process excision and with transverse process and mastoid process excision)as well as an annulus fibrosus puncture model,and to compare and evaluate the characteristics of the three models.METHODS:Forty male adult Sprague-Dawley rats were randomly divided into four groups(n=10 per group):sham surgery group,spinous process group,transverse process group,and annulus fibrosus puncture group.In the sham surgery group,surgical preparation was performed,the skin was incised,and the spinous process was exposed,and then sutured.In the spinous process group,L5 spinous process and transverse process were excised,and two pieces of tail nucleus pulposus were placed in the intervertebral foramen.In the transverse process group,L5 transverse process and transverse process were excised,and two pieces of tail nucleus pulposus were placed in the intervertebral foramen.In the annulus fibrosus puncture group,the transverse process was excised and annulus fibrosus puncture and intervertebral disc injection of interleukin 1β were then performed.Thermal paw withdrawal latencies were tested before and after modeling.Lumbar spine MRI was performed 2 weeks after modeling.Pathological changes in the intervertebral discs were observed using hematoxylin-eosin staining and safranin-O-fast green staining.Immunofluorescence was used to observe CD68+positive expression.RESULTS AND CONCLUSION:(1)Thermal withdrawal threshold testing results showed that compared with the sham surgery group,pain sensitivity and tolerance time of rats decreased significantly after modeling(P<0.05).(2)Lumbar spine MRI images showed that the spinous process and transverse process groups had obvious protrusion of nucleus pulposus tissue,which more closely resembled MRI images of patients with common lumbar disc herniation.(3)Hematoxylin-eosin staining revealed that compared with the sham surgery group,nucleus pulposus tissues in the model groups showed varying degrees of degeneration,inflammatory cell infiltration,and degradation of spinal cord cells,with the appearance of cystic changes,among which the annulus fibrosus puncture group had the most severe pathological changes.(4)Safranin-O-fast green staining showed that compared with the sham surgery group,the boundaries of nucleus pulposus tissues in the three model groups were blurred,with extensive inflammatory reactions and varying degrees of degeneration in the annulus fibrosus.(5)CD68+immunofluorescence staining results showed that compared with the sham surgery group,the expression of CD68+in the model groups was higher and more widespread,with the annulus fibrosus puncture model showing the highest expression.All the three methods could be used to effectively establish rat models of lumbar disc herniation,with the annulus fibrosus puncture model established after excision of the transverse process being superior to the autologous nucleus pulposus transplantation model(spinous process+mastoid process),and the first two models being superior to the autologous nucleus pulposus transplantation model(transverse process+mastoid process).

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Purpose To explore the value of quantitative parameters(T2* value,R2* value)of three-dimensional multi-echo ultrashort echo time technique for the differential diagnosis of benign and malignant pulmonary nodules and masses(PNMs).Materials and Methods The MRI data of 68 patients with PNMs in Xi'an Gaoxin Hospital from July 2021 to October 2022 were retrospectively analyzed,and PNMs were grouped into benign(34 cases)and malignant(34 cases)categories using histopathology or clinical follow-up as the reference standard.Two observers respectively outlined the regions of interest on three-dimensional multi-echo ultrashort echo time-T2* and R2* maps,and quantitatively measured the T2* and R2* values.The intraclass correlation coefficient(ICC)was used to evaluate the consistency of the measured values.Differences in the above indicators between the two groups of PNMs were analyzed,and their diagnostic efficacy was assessed.The predictive probability of the combined two indicators was computed,the receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated.Results The measurement results of each parameter of PNMs in the benign and malignant groups by the two observers were consistent(ICC>0.75).The T2* value of the malignant group was higher than that of the benign group(Z=-5.158,P<0.001),and the R2* value was lower than that of the benign group(Z=-4.845,P<0.001),and the differences were statistically significant.The AUC of the T2* value was 0.864(95%CI 0.775-0.953,P<0.001),with a maximum Youden index of 0.677,a threshold of 9.675 ms,a sensitivity of 76.5%,and a specificity of 91.2%.The AUC of the R2* value was 0.842(95%CI 0.746-0.937,P<0.001),with a maximum Youden index of 0.647,and a threshold of 109.15/s,with a sensitivity of 73.5%and a specificity of 91.2%.The AUC of the combined diagnosis of T2* and R2* values was 0.867(95%CI 0.779-0.955,P<0.001),with a maximum Youden index of 0.677,a sensitivity of 82.4%,and a specificity of 85.3%.There was no statistically significant difference in the pairwise comparison of T2* values,R2* values,and their combined AUC(all P>0.05).Conclusion The T2* value and R2* value of the three-dimensional multi-echo ultrashort echo time technique,as well as the combination of the two indicators,are all helpful in differentiating benign and malignant PNMs,providing imaging support for the preoperative non-invasive and precise differentiation of PNMs and optimizing clinical diagnosis and treatment decisions.

Rectal cancer is one of the most common gastrointestinal malignant tumors,and patients with early rectal cancer can achieve radical tumor resection by surgical treatment alone,while most patients with rectal cancer are in the locally advanced stage when admitted to hospital.For this group of people,it is difficult to obtain a good prognosis through surgical treatment alone,and interventional chemoradio-therapy before surgery is of important clinical significance.A large number of clinical studies have proved that preoperative neoadjuvant therapy can effectively reduce tumor stage,increase pathological complete response(pCR)rate,thereby greatly improving the prognosis of patients.At present,the core methods of neoadjuvant therapy for locally advanced rectal cancer are radiotherapy and chemotherapy,as well as the emerging targeted therapy and immunotherapy,while the optimal combination order of various treatments remains in dispute.This article summarizes various neoadjuvant therapy regimens in recent years,in order to provide evidence for the multidisciplinary and comprehensive treatment of rectal cancer.

Objective:To explore the protective mechanism of dexmedetomidine (Dex) in a model of broncho-pulmonary dysplasia (BPD) in mice exposed to hyperoxia.Methods:Neonatal rats were randomly assigned to four groups:air control group,hyperoxia injury group,Dex control group,and hyperoxia+Dex group,with six animals in each group.The air control and Dex control groups were exposed to ambient air,while the hyperoxia injury and hyperoxia+Dex groups were exposed to 90% O 2.The Dex control and hyperoxia+Dex groups received daily intraperitoneal injections of Dex at a dosage of 500 μg/kg.Lung tissue samples were collected after 7 days.Histomorphological changes in lung tissue were evaluated using hematoxylin and eosin (HE) staining,and mitochondrial ultrastructural changes in type I epithelial cells of neonatal rat lung tissue were observed via transmission electron microscopy.The activity of Complex Ⅰ in neonatal rat lung tissue was assessed.The expression levels of PINK1 and Parkin in neonatal rat lung tissue were measured using quantitative PCR (qPCR).Western blot analysis was conducted to determine the protein expression levels of PINK1 and Parkin in lung tissues. Results:Under transmission electron microscopy,mitochondrial structures were intact in the lung tissues of both the air control group and the Dex control group.However,significant mitochondrial damage was observed in the hyperoxia injury group,while the hyperoxia+Dex group exhibited some relief from mitochondrial damage compared to the hyperoxia injury group.The activity of the oxidized respiratory chain Complex Ⅰ in the hyperoxia injury group was significantly lower than that in the air control group (4.824±0.804 vs.15.276±0.804, P<0.05) and the hyperoxia+Dex group(4.824±0.804 vs.9.648±0.804, P<0.05).After qPCR analysis,the expression levels of PINK1 and Parkin in the hyperoxia injury group were higher than those in the air control group(1.80±0.06 vs.1.00±0.07,2.10±0.14 vs.1.00±0.09, P<0.05),but lower than those in the hyperoxia+Dex group(1.80±0.06 vs.3.61±0.19,2.10±0.10 vs.4.24±0.43, P<0.05).Western blot analysis revealed that the expression levels of PINK1 and Parkin in the hyperoxia injury group were higher than those in the air control group(2.16±0.11 vs.1.00±0.01,3.82±0.13 vs.1.00±0.01, P<0.05),but lower than those in the hyperoxia+Dex group(2.16±0.11 vs.3.35±0.14,3.82±0.13 vs.5.48±0.15, P<0.05).There were no significant differences in mitochondrial structure integrity,Complex Ⅰ enzyme activity,or the expression levels of PINK1 and Parkin,as assessed by qPCR and Western blot analysis,between the air control and Dex control groups( P>0.05). Conclusion:Dex effectively mitigates mitochondrial ultrastructural damage in BPD model mice,enhances the activity of Complex Ⅰ in the oxidative respiratory chain,reduces mitochondrial damage,and increases the activation of the PINK1-Parkin-mediated mitophagy pathway,thereby promoting lung protection.

Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.