Objective:To evaluate the extracorporeal membrane oxygenation (ECMO) related outcomes during hospitalization during the intensive care unit (ICU) in idiopathic pulmonary fibrosis (IPF) patients with high body mass index (BMI, >25 kg/m 2) undergoing lung transplantation with ECMO support. Methods:A retrospective observational study was conducted. IPF patients who received ECMO during lung transplantation admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from 2019 to 2020 were enrolled. Preoperative indicators including, demographics, comorbidities, arterial blood gas, and laboratory indicators; intraoperative indicators, such as lung lobe volume reduction, surgical type, surgical time, cold ischemia time, blood loss and transfusion volume; immediate indicators upon admission to the ICU, such as blood gas analysis and laboratory indicators; ECMO related outcomes, such as ECMO mode, ECMO support time, ECMO related complications (bleeding at the catheterization site, intraductal thrombosis, lower limb ischemia), and the length of ICU stay, duration of mechanical ventilation, and 30-day survival rate were collected. According to BMI, patients were divided into three groups: light weight group (BMI < 18.5 kg/m 2), normal weight group (BMI 18.5-24.9 kg/m 2), and overweight group (BMI ≥ 25.0 kg/m 2). Mainly to compare the relevant outcomes of ECMO among patients during ICU. Results:A total of 114 IPF patients who received ECMO support during lung transplantation were collected, including 23 cases in the light weight group, 63 cases in the normal weight group, and 28 cases in the overweight group. Compared with patients with underweight and normal weight, overweight patients were more likely to have hypertension (46.4% vs. 8.7%, 23.8%, P < 0.01) and coronary heart disease (32.1% vs. 4.3%, 20.6%, P < 0.05) before surgery, which was consistent with international guidelines for obesity. Other clinical data (preoperative, intraoperative, ICU characteristics) showed no statistically significant differences and were comparable. There was no statistically significant difference in terms of ECMO related outcomes, such as ECMO related complications [veno-venous (V-V) mode: 78.3%, 77.8%, 78.6%, veno-arterial (V-A) mode: 21.7%, 22.2%, 21.4%], ECMO support time (hours: 61.70±20.03, 44.57±5.76, 41.77±7.26), ECMO related complications (bleeding at the catheterization site: 4.3%, 7.9%, 14.3%; intraductal thrombosis: 8.7%, 12.7%, 17.9%; lower limb ischemia: 8.7%, 12.7%, 14.3%), and the length of ICU stay (days: 11±3, 7±1, 9±1), duration of mechanical ventilation [days: 2 (2, 11), 2 (2, 6), 3 (2, 8)] among the light weight group, normal weight group, and overweight group (all P > 0.05). Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 30-day cumulative survival rate among the three groups (Log-Rank test: χ2 = 0.919, P = 0.632). Conclusions:High BMI does not worsen ECMO-related outcomes or adversely affect early prognosis in IPF patients undergoing lung transplantation. BMI as a single parameter should not be a contraindication for the use of ECMO in lung transplantation surgery for IPF patients.

Houttuynia cordata,which can be taken as a food and medicine,is one of the traditional Chinese herbs in China.Houttuynia cordata is rich in chemical components like volatile oils,flavonoids,alkaloids,phenylpropanoids,and steroids etc.Modern studies have shown that Houttuynia cordata has anti-inflammatory,anti-tumor,antibacterial,antiviral,and other pharmacological effects.In this paper,herbal textual research,chemical composition and pharmacological effects of Houttuynia cordata were integrated and summarized.The quality markers of Houttuynia cordata were predicted and analyzed according to the concept of quality markers of traditional Chinese medicine in terms of phytopharmacology,medicinal properties and medicinal efficacy,different production areas and harvesting period,constituents absorbed in the blood and chemical components measurability.The aim is to provide references for the quality control study of Houttuynia cordata.

With the maturity and development of surgical techniques,as well as the improvement of perioperative management level,the success rate of kidney transplantation has been significantly improved.However,due to evident differences in heredity and antigenicity between donors and recipients,rejection will occur after kidney transplantation,which will affect the survival of renal grafts.Immunosuppression is an important treatment for rejection,which is of significance to reduce the risk of rejection and enhance graft survival rate.Nevertheless,immunosuppressants may cause multiple complications while lowering the incidence of rejection,such as infection,cardiovascular diseases and tumors,etc.,which seriously affect the quality of life of patients and may even lead to their death.Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts.In this article,the development history of organ transplantation,immune induction therapy and immune maintenance therapy was reviewed,and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed,aiming to provide reference for improving clinical prognosis of kidney transplant recipients.

Objective To summarize the modeling methods and standards of thyroid cancer,to provide reference for the establishment of thyroid cancer animal model close to the clinical syndrome of Chinese and Western medicine,and to promote the progress of clinical diagnosis and treatment.Methods The modeling methods and characteristics of animal models of thyroid cancer in CNKI,Wanfang,Web of Science and PubMed databases were analyzed and summarized.The advantages and disadvantages were evaluated,and the coincidence degree with the clinical characteristics of traditional Chinese and Western medicine was analyzed.Results There are many modeling methods for thyroid cancer animal models,which are mainly divided into four types:spontaneous,induced,genetic engineering and transplantation models.Genetic engineering mouse models include transgenic models,gene knockout models,gene replacement models and the latest reported restricted mouse models.Among them,the genetic engineering mouse model and the transplanted mouse model have a high clinical coincidence,and the spontaneous and induced tumor model have a low clinical coincidence.Conclusion It is one of the important directions for future research on thyroid cancer to establish an animal model consistent with"TCM syndrome"and"Western medicine diagnostic criteria".

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

ObjectiveTo explore the mechanism of Dendrobium huoshanense polysaccharide （DHP） against inflammatory damage of neurons in Parkinson's disease （PD） model. MethodSH-SY5Y cells were randomized into blank group， model group， and DHP group. The survival rate of cells was measured by thiazole blue（MTT） assay， and the levels of lactate dehydrogenase （LDH）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） were measured by colorimetric analysis. BV-2 microglia were classified into blank group， model group， DHP group， and MCC950 group （positive control group）， and enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. The expression of NOD-like receptor protein 3 （NLRP3）， adaptor protein apoptosis-associated dot protein （ASC）， cysteine aspartic protease-1 （Caspase-1）， and IL-1β was measured by Western blot. A total of 50 C57BL/6 mice were randomized into blank group， model group， DHP low-dose （100 mg·kg^-1） group， DHP equivalent-dose （350 mg·kg^-1） group， and MCC950 group （positive control group）， 10 mice in each group. The motor balance and coordination of C57BL/6 mice were observed by beam walking test， tail suspension test and rotarod test. The levels of Iba-1 and tyrosine hydroxylase （TH） were detected by immunofluorescence staining. The damage of dopaminergic neurons in the substantia nigra was detected by FJB staining. The levels of inflammatory factors such as IL-1β， IL-18， and TNF-α in mouse midbrain tissues were detected by ELISA and the protein levels of NLRP3， ASC， Caspase-1， and IL-1β protein were measured by Western blot. ResultCompared with the blank group， the SH-SY5Y model group showed decreased cell survival， increased levels of LDH， ROS， and MDA （P<0.05）， and decreased levels of SOD （P<0.05）. Compared with the model group， the DHP group demonstrated increased cell survival， decreased levels of LDH， ROS， and MDA （P<0.01）， and increased level of SOD （P<0.01）. Compared with the blank group， BV-2 model group had high levels of IL-1β， IL-18， and TNF-α （P<0.05） and high protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.05）. Compared with the model group， DHP and MCC950 groups demonstrated low levels of IL-1β， IL-18， and TNF-α （P<0.01） and low protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.01）. Compared with the blank group， the C57BL/6 model group displayed long time to pass the balance wood （P<0.05）， short time spent on the rod in the rotarod test （P<0.05）， high levels of IL-1β， IL-18， and TNF-α （P<0.05） and expression of Iba-1 in the midbrain substantia nigra （P<0.05）， low TH expression （P<0.05）， more positive neurons in the FJB staining （P<0.05）， and high expression of NLRP3， Caspase-1， ASC， and IL-1β proteins （P < 0.05）. Compared with the model group， the mice in the DHP and MCC950 groups had short time to pass the balance beam （P<0.01）， long time spent on the rod （P<0.01）， low levels of IL-1β， IL-18， and TNF-α （P<0.01）， low Iba-1 expression in midbrain substantia nigra （P<0.01）， high TH expression （P<0.01）， and small number of positive neurons in the midbrain substantia nigra （P<0.01）. The expression of NLRP3， ASC， and IL-1β proteins was lower in the MCC950 group （P<0.01）， and the expression of NLRP3， ASC， Caspase-1 and IL-1β proteins was lower in the DHP equivalent-dose group （P<0.01） than in the model group. ConclusionDHP has anti-oxidative stress effect. It regulates the expression of NLRP3 inflammasome and inhibits the overactivation of microglia， thereby alleviating the neuroinflammatory injury in PD and exerting the neuroprotective effect.

ObjectiveTo explore the macroscopic medication pattern of traditional Chinese medicine （TCM） in treating esophageal cancer （EC） and provide medication references for the clinical application of TCM in EC treatment. MethodRelevant literature on TCM treatment of EC was retrieved from three major Chinese databases： China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP. Information about Chinese herbal medicines was entered into Excel to establish a prescription database for EC. The data were standardized， summarized， and subjected to frequency analysis， association rules， and cluster analysis of medication in the prescriptions. Based on the TCM classification of EC syndromes， clinical indications corresponding to each syndrome were identified， and high-frequency drugs and drug pairs were analyzed correspondingly with syndromes. ResultA total of 136 prescriptions containing 240 Chinese herbal medicines were screened， with a cumulative frequency of 1 853 times. The top 5 frequently used Chinese herbal medicines were Glycyrrhizae Radix et Rhizoma， Poria， Atractylodis Macrocephalae Rhizoma， Astragali Radix， and Pinelliae Rhizoma. In terms of functions， the Chinese herbal medicines were mainly deficiency-tonifying， urination-promoting and dampness-draining， deficiency-tonifying， deficiency-tonifying， and phlegm-resolving and cough and dyspnea-relieving ones. The statistical analysis of flavor， property， and meridian tropism showed that Chinese herbal medicines were mainly bitter and sweet， warm， cold， and neutral， and acted on the spleen， lung， and stomach meridians. Association rule analysis yielded nine potential drug combinations， and cluster analysis of high-frequency drugs resulted in four combination categories. The four TCM syndromes for EC corresponded to respective clinical indications， treatment drugs， and drug pairs. ConclusionTonifying deficiency， reinforcing healthy Qi， descending adverse Qi， resolving phlegm， activating blood， and resolving stasis are the basic principles of TCM treatment for EC， which are supplemented by clearing heat and dissipating mass while focusing on regulating and smoothing the qi movement. The drug combinations obtained from high-frequency drug and association rule analysis provide references for different TCM syndrome treatments of EC， offering valuable insights for clinical medication.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Objective To explore the major risk factors of post transplantation diabetes mellitus (PTDM) and analyze the correlation between tacrolimus and PTDM after kidney transplantation. Methods Clinical data of 123 kidney transplant recipients were collected. All recipients were divided into the PTDM group (n=19) and non-PTDM group (n=104). Clinical data of all recipients in two groups were analyzed. The risk factors of PTDM were analyzed by binary logistic regression. Twenty-four mice were evenly divided into the control group (normal saline), low-dose tacrolimus (0.1 mg/kg), medium-dose tacrolimus (0.75 mg/kg) and high-dose tacrolimus groups (1.5 mg/kg). The solutions were given twice a day. The effect of tacrolimus on blood glucose metabolism in mice was evaluated. Results The incidence of PTDM was 15.4% (19/123) within 1 year after kidney transplantation. Age≥48 years old and the trough concentration of tacrolimus≥9 ng/mL within 3 months after kidney transplantation were the risk factors for PTDM after kidney transplantation (both P < 0.05). The fasting blood glucose levels of mice after administration in the low-, medium- and high-dose tacrolimus groups were significantly lower than those before administration (all P < 0.05) in a dose-independent manner (P=0.750). In the low-, medium- and high-dose tacrolimus groups, the postprandial blood glucose levels of mice after administration were significantly higher than those before administration (all P < 0.05) in a dose-dependent manner (P=0.012). Conclusions Tacrolimus is intimately correlated with the incidence of PTDM after kidney transplantation. Age≥48 years old and the trough concentration of tacrolimus ≥9 ng/mL within 3 months after kidney transplantation are the independent risk factors of PTDM. Tacrolimus affects the postprandial blood glucose levels of mice in a dose-dependent manner.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.