Sepsis is a multi-organ dysfunction syndrome caused by infection and immune dysfunction, with a high mortality rate. It affects multiple important organs such as the heart, lungs, kidneys, liver, and brain. Establishing corresponding animal models of organ dysfunction syndrome is an essential step in clarifying its pathogenesis, researching potential effective drugs, and evaluating the effectiveness and safety of treatment plans. This article first summarizes classic modeling methods for sepsis related organ injury, including the destruction of intestinal barrier tissue integrity and the implantation of pathogens or toxic drugs. The former mainly includes cecal ligation and puncture, ascending colon stent implantation, and cecal ligation incision. The latter is divided into intraperitoneal injection, intravenous injection, and intratracheal administration based on the clinical infection route being simulated. Cecal ligation and puncture and lipopolysaccharide intraperitoneal injection are the most commonly used methods. Secondly, this article summarizes the common modeling methods and evaluation methods for animal models of sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction. It points out that almost all organ injuries use classic modeling methods, and different organ injury models have additional modifications according to their different pathogenesis. For example, in addition to the classic modeling methods, lipopolysaccharide instillation in the trachea is more effective in modeling acute lung injury as it better simulates lung barrier dysfunction. Cecal ligation and puncture followed by Pseudomonas instillation in the trachea in a secondary challenge model better represents sepsis-induced acute kidney injury. Intraperitoneal injection of galactosamine is a mature modeling method of sepsis-induced acute liver injury. Intracerebral injection of lipopolysaccharide is a feasible model of sepsis-associated encephalopathy. In addition to the different modeling methods, there are differences in the administration time, dosage and experimental time points according to the different experimental purposes. This article reviews the research progress of animal experimental models for sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction, aiming to provide a reference for the selection of animal experimental models and optimization of experimental design.

Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Benzofurans/therapeutic use* ; Double-Blind Method ; Treatment Outcome

Objective:Charcot-Marie-Tooth disease (CMT) comprises a group of clinically and genetically heterogeneous inherited neuropathies with an estimated prevalence of 1 in 2500. This study aimed to analyze the clinical and mutational characteristics of Chinese CMT patients with MFN2, BSCL2 and LRSAM1 variants.Methods:In this study, genetic analysis was performed in 206 Chinese patients at Chinese PLA General Hospital from December 2012 to March 2020 with clinical diagnosis of CMT, and reported variants of MFN2, BSCL2 and LRSAM1 related to CMT2.Results:We reported ten MFN2 mutations in ten unrelated patients (7 male, 3 female), two of whom had positive family history. Three novel mutations were detected including c.475-2A>G (splicing); c.687dupA (p.E230Rfs*16) and c.558dupT (p.S186fs). We reported three BSCL2 mutations of four unrelated patients, including c.461C>G (p.S154W), c.461C>T(p.S154L), and novel variants of c.1309G>C (p.A437P) and c.845C>T (p.A282V). Furthermore, two novel variants of LRSAM1, including c.1930G>T (p.G644C) and c.1178T>A (p.L393Q) were detected in two unrelated patients.Conclusion:Mutational spectrum of MFN2-, BSCL2-and LRSAM1-related CMT disease is expanded with the identification of novel variants in Chinese patients.

Objective:To study the effect of Helicobacter pylori (HP) infection on the standardized dose of postoperative thyrotropin suppression of differentiated thyroid carcinoma.Methods:A total of 82 patients diagnosed with differentiated thyroid carcinoma and receiving total thyroidectomy in Beijing Rehabilitation Hospital affiliated to Capital Medical University from Jan. 2019 to Jun. 2020 were enrolled in this study prospectively.19 patients with higher standardized dose of the thyrotropin suppression (>2.5 μg·kg -1·d -1) were selected as the experimental group, and 63 patients with the lower standardized dose of the thyrotropin suppression (≤2.5 μg·kg -1·d -1) were selected as the control group. The presence of HP infection was measured by C13 method, and the HP infection rate was compared between the two groups. The patients with HP infection in the experimental group received standard quadruple therapy to eradicate Helicobacter pylori. The standardized dose before and after treatment were observed and compared. Results:The HP infection rate in the experimental group (73.7%, 14/19) were significantly higher ( P<0.05) than those in the control group (31.7%, 20/63). In the experimental group, 14 patients with HP infection in the experimental group received standard quadruple therapy to eradicate HP. HP was successfully eradicated in 11 patients after the treatment (one patient quit the treatment before completion, the actual eradication rate was 84.6%) ; Eight weeks after the treatment, the dose adjustment of thyrotropin suppression reached steady-state in 13 patients completed the therapy. The average standardized dose was (2.15±0.25) μg·kg -1·d -1, significantly lower than that before treatment [ (2.89±0.21) μg·kg -1·d -1] ( P<0.05) . Conclusions:HP infection may be an important factor affecting the standardized dose of thyrotropin suppression in postoperative patients with thyroid cancer. For those patients with HP infection, eradication treatment of HP can significantly reduce the standardized dose and treatment-related complications.

Objective:To assess the long-term outcome and influencing factors of laparoscopic Heller myotomy plus Dor fundoplication(LHM+ Dor) for achalasia by a single operator.Methods:Fifty-four patients who underwent LHM+ Dor consecutively from January 2011 to December 2019 were retrospectively reviewed. Those who had already undergone surgical or endoscopic myotomy and who were complicated with cancer were ruled out. Symptom inquiry and esophagogram were conducted both before and after surgery for assessing surgical results. Esophagoscopy, esophageal manometry and 24 h pH monitoring were performed before surgery, and the effects of these preoperative factors on the long-term outcome were analyzed.Results:All patients had dysphagia for average 6.5 years, ranging from 0.5-30.0 years. Intra-operative mucosal perforation occurred in 4(7.4%) patients, and there were no postoperative morbidity and mortality. At a median follow-up of 5.2 years, the morbidity of dysphagia decreased from 100% before surgery to 5.5% after surgery( P<0.001), Eckardt scores from 4.85±1.64 to 0.71±1.08( P=0.000). After surgery, 94.4% of patients had excellent and good relief of symptoms and good control of gastroesophageal reflux, the morbidity of heartburn being 3.7%. At 5 years after surgery, the probability of being symptoms free(Eckardt score≤1) was 91.7% in patients without preoperative night cough, compared to 54.6% in those with preoperative night cough( P=0.047). The probability was 92.3% in patients with grade Ⅰ and Ⅱ dilation of the esophagus and 79.0% in patients with grade Ⅲ and Ⅳ dilation( P=0.027). At multivariate analysis, heavier esophageal dilation was the independent predicator for poor symptom control after surgery. Conclusion:LHM+ Dor can be safely performed and durably relieve achalasia symptoms. Severe esophageal dilation before surgery is an independent predictor of a poor response to surgery.

Objective:To explore the effective method for treatment of small and short penis after hypospadias surgery.Method:s From November 2017 to November 2018, 57 children aged 4 to 14[mean age(7.91±2.89)years] with hypospadias who met the diagnostic criteria of small penis were reexamined at the First Affiliated Hospital of Xin-xiang Medical University.They were randomly divided into the physical treatment group and the drug treatment group according to the order of visits, and the untreated patients were included in the control group.Among them, 21 patients in the physical treatment group were treated with penile rehabilitation therapy apparatus, supplemented by Salvia mil-tiorrhiza bath (30 minutes/time, once/day, 10 days), and 20 patients in the drug treatment group were treated with Testosterone cream topically (3 times/day, 10 days). Penile relaxation length, stretch length, transverse and longitudinal diameters of glans in 2 groups before and after the treatment were measured.The relevant indexes of 16 patients in the control group measured before and after 10 days and compared with those in the treatment group.Result:s (1)The penile relaxation length in the physical treatment group increased from (25.48±6.13) mm to (30.72±6.49) mm, the length of stretch increased from (34.90±7.71) mm to (41.08±8.43) mm, the transverse diameter of glans increased from (14.81±3.40) mm to (16.57±3.42) mm, and the longitudinal diameter increased from (13.94±3.15) mm to (15.82±3.52) mm, and the differences were statistically significant (all P<0.05). (2)The penile relaxation length in the drug treatment group increased from (21.07±4.26) mm to (31.32±4.72) mm, the length of stretch increased from (31.94±7.96) mm to (45.39±7.24) mm, the transverse diameter of glans increased from (13.38±1.77) mm to (16.64±2.10) mm, and the longitudinal diameter increased from (13.09±1.77) mm to (16.62±1.86) mm, and the differences were statistically significant (all P<0.05). (3)There was no significant difference in penile relaxation length, the length of stretch, transverse diameter and longitudinal diameters of glans before and after 10 days in the control group (all P>0.05). (4) Compared with the control group, the penile relaxation length, the length of stretch, transverse diameter and longitudinal diameters of glans in the physical treatment group increased significantly, and the differences of growth values between the two groups were statistically significant (all P<0.05). (5) Compared with the control group, the penile relaxation length, the length of stretch, transverse diameter and longitudinal diameters of glans in the drug treatment group also increased significantly, and the difference of growth values between the two groups were statistically significant (all P<0.05). (6) The growth of penile relaxation length, the length of stretch and transverse and longitudinal diameters in the drug treatment group were higher than those in the physical treatment group, and the difference of growth values were statistically significant (all P<0.05). Conclusions:Both the negative pressure suction method and topical application of Testosterone cream are effective in the treatment of small and short penis after hypospadias surgery.However, Testosterone cream is difficult to obtain, and the treatment of negative pressure suction is simple, noninvasive, painless and free of adverse reactions.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered MSC accumulated in the lung. Both MSC/A549 cell experiments and MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.