Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Delayed diagnosis of alpha-1-antitrypsin deficiency following post-hepatectomy liver failure: A case report

Post-hepatectomy liver failure(PHLF) is a leading cause of morbidity and mortality following major liver resection. The development of PHLF is dependent on the volume of the remaining liver tissue and hepatocyte function. Without effective pre-operative assessment, patients with undiagnosed liver disease could be at increased risk of PHLF. We report a case of a 60-year-old male patient with PHLF secondary to undiagnosed alpha-1-antitrypsin deficiency(AATD) following major liver resection. He initially presented with acute large bowel obstruction secondary to a colorectal adenocarcinoma, which had metastasized to the liver. There was no significant past medical history apart from mild chronic obstructive pulmonary disease. After colonic surgery and liver directed neo-adjuvant chemotherapy, he underwent a laparoscopic partially extended right hepatectomy and radio-frequency ablation. Post-operatively he developed PHLF. The cause of PHLF remained unknown, prompting reanalysis of the histology, which showed evidence of AATD. He subsequently developed progressive liver dysfunction, portal hypertension, and eventually an extensive parastomal bleed, which led to his death; this was ultimately due to a combination of AATD and chemotherapy. This case highlights that formal testing for AATD in all patients with a known history of chronic obstructive pulmonary disease, heavy smoking, or strong family history could help prevent the development of PHLF in patients undergoing major liver resection.

3-Dimensional Kinematic Comparison of Arm Movements between an Individual with NGLY1 Deficiency and a Neurotypical Individual

NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.

Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease

AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.

Role of bisphosphonates in osteoporosis caused by adult growth hormone deficiency

In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Study on improving hematopoietic function of rats with blood deficiency syndrome by Shengxuebao mixture

Background:Shengxuebao mixture(SXBM)is a novel herbal drug approved by China State Food and Drug Administration for the treatment of Leukopenia and iron deficiency anemia caused by radiotherapy and chemotherapy.Methods:To explore the mechanism of SXBM in treating blood deficiency syndrome(BDS).Firstly,network pharmacology and in vivo experiments were used to screen candidate targets and important signaling pathways of SXBM,GO functional enrichment and KEGG pathway analysis were performed.Secondly,a BDS rat model was established to verify the results of the analysis of network pharmacological enrichment.Histopathology and routine peripheral blood examination were observed.The expressions of tumor necrosis factor-α,interleukin(IL)-6,HIF-1αand NF-κB were detected by Western blot,and the expressions of IL-6,IL-1βwere detected by ELISA.Results:62 bioactive components,66 potential targets and 131 signaling pathways of BDS were successfully identified by network pharmacology.Molecular docking simulation techniques showed that key targets tumor necrosis factor-α,IL-6,IL-1βcan dock well with crucial components,and the BDS-related signaling pathways HIF-1 and JAK-STAT play a vital role.The combined model experiment of acetylphenylhydrazine and cyclophosphamide showed that the model group had obvious blood deficiency,and the histopathology and blood routine were effectively restored after administration.Our findings indicate that SXBM’s therapeutic effect on BDS primarily involves the mediation of the HIF-1α/NF-κB signaling pathway and the regulation of hematopoietic factor expression.Conclusion:This study not only affirmed the protective properties of SXBM against BDS but also provided insights into a potential mechanism for blood replenishment in the treatment of BDS using SXBM.

Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

AIM： To test the hypothesis that the variant UDP- glucuronosyltransferase 1A1 （UGT1A1） gene, glucose-6- phosphate dehydrogenase （G6PD） deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS： A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS： Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A（TA）6 TAA/A（TA）TTAA （6/7）, heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene （P = 0.012, Z2 test）, but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia （2.7% vs 2.4% and 5.1% vs 5.1%, respectively）. The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog （18.0±6.5 and 12.7±2.9 μmol/L, respectively; P〈0.001, Student＇s ttest）.CONCLUSION： Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese. 2005 The WJG Press and Elsevier Inc. All rights reserved

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum:Two case reports

BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Study on the Expression of Organic Anion Transporting Polypeptide (oatp2a1) in Rat with Spleen Deficiency Syndrome and the Exploration of Clinical Significance

Objective: to explore the mechanism of transportation and transformation of dampness by the way of the expression of organic anion transporting polypeptide (oatp) superfamily member 2a1 (oatp2a1) mRNA in rat with spleen deficiency syndrome and the significance in transportation and transformation of dampness. Methods: 32 wistar male rats were divided randomly into four groups: normal group (n = 6), normal + AA group (n = 6), spleen deficiency group (n = 10), Spleen deficiency + AA group (n = 10). After reserpine-induced spleen deficiency model was made, intragastric administration of aristolochic acid (AA) was adopted for three days, the expression of oatp2a1 mRNA were detected in the tissues of lung, liver, kidney, stomach, small intestine and large intestine in four groups by using Fluorescent Quantitative-Polymerase Chain Reaction (FQ-PCR). Results: the expression of oatp2a1 mRNA in above six tissues could be detected. The ex-pression of oatp2a1 mRNA in liver tissue of rat with spleen deficiency syndrome was up-regulated compared to normal group (P = 0.035, P < 0.05), the expression of oatp2a1 mRNA in small intestinal tissue of rat with spleen deficiency syndrome was down-regulated compared to normal group (P = 0.004, P < 0.01), the expression of oatp2a1 in intestinal tissue in normal + AA group is down-regulated compared to normal group (P = 0.032, P < 0.05). Conclusions: oatp2a1 might be one of the material basis involved in transportation and transformation of dampness. The changes of expression of oatp2a1 mRNA in small intestine, liver tissue suggests that small intestine, liver might play an important role in the transportation and transformation of dampness in the state of spleen deficiency. We further concluded that the function of spleen’s governing transportation and transformation of dampness was not only including the function of the gastrointestinal, but also part of the liver function in some degree, which needs to be further studied.

Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients

BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.

A critical role of HMGB1 in liver tumor development under autophagy deficiency

Objective:Autophagy is important for cellular homeostasis.It has been well documented that while autophagy can be important for cancer cell survival,it can also be a tumorsuppressing mechanism in normal cells.Mice with hepatic autophagy deficiency develop liver tumors,but the mechanisms of tumorigenesis are not known.Methods:Atg7-or Atg5-deficient mice and their counterparts with additional genetic deficiencies in other genes.

Improvement in human immunodeficiency virus-1/acquired immune deficiency syndrome patients' well-being following administration of “Phyto V7”

AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not undergoing antiretroviral treatment.METHODS:Two hundred and thirty nine HIV-1 seropositive male and female voluntary inmates were recruited through the Uruguay National Program of AIDS.The study participants received for 90 consecutive days every eight hours two tablets(760 mg/each) of Phyto V7,containing a mix of the following phytochemicals:flavonols(Kaempferol,Quercetin),flavones(Apigenin,Luteolin),hydroxycinnamic acids(ferrulic acid),carotenoids(Lutein,Lycopene,Beta carotene) and organosulfur compounds,all from vegetal origin.The participants did not receive any antiretroviral treatment during the study.At days 0,30,60 and 90(± 2 d) the participants were evaluated for body mass index(BMI),tolerance to Phyto V7 and Index of Quality of Life based on the Karfnosky scale.ANOVA,Tukey Post-test,χ2 test and Wilcoxon Signed Rank test were used to analyze the effect of treatment.RESULTS:One hundred and nighty nine study participants finished the study.Already after 30 d of Phyto V7 consumption,the weight,BMI and Karnofsky score statistically significantly improved(P < 0.001),and continued to improve until the end of the study.The mean weight gain per participant during the 90 d wasof 1.21 kg(approximately 2% of body weight).The overall increase in the mean Karnofsky score after 90 d was 14.08%.The lower the BMI and Karnofsky score of the participants were at the beginning of the study,the more notorious was the improvement over time.For example,the mean increment of Index of Quality of Life,among the participants with an initial Karnofsky score of 5 or below(n = 33) from day 0 to day 90,was of 35.67%(0.476 ± 0.044 vs 0.645 ± 0.09; P < 0.001).The tolerability to Phyto V7 was very good and no adverse reactions were recorded or reported.CONCLUSION:Administration of the Phyto V7 can be an important tool to improve the well-being of HIV-1 seropositive individuals and AIDS patients,not undergoing antiretroviral treatment.

Managing panniculitis in alpha-1 antitrypsin deficiency: Systematic review of evidence behind treatment

AIM To systematically review literature for management of alpha-1 antitrypsin deficiency(AATD) panniculitis. METHODS Multiple databases were searched using combinations of pertinent terms. Articles were selected describing panniculitis treatment in patients with AAT < 11 μmol and/or PiZZ genotype, with no language limitation. All relevant articles were accessed in full text. Independent review of abstracts and full manuscripts was conducted by 2 reviewers, and quality assessment by one reviewer(checked by a second). Data extraction was conducted byone reviewer(checked by a second). Narrative synthesis only was conducted, as data were unsuitable for metaanalysis.RESULTS Thirty-two case reports and 4 case series were found. Augmentation therapy(infusions of plasma-derived AAT) was the most successful, with complete resolution of symptoms in all patients. Dapsone is a less expensive option, and it achieved clinical resolution in 62% of patients, but it is very poorly tolerated. Among other single-agent antibiotics, doxycycline was the most successful with complete clinical resolution seen in 33% of patients. Immunosuppressants were largely unsuccessful; 80% of patients exhibited no response. Liver transplantation and therapeutic plasma exchange displayed complete resolution in 66% of patients. Other strategies, such as non-steroidal anti-inflammatory drugs or antibiotics other than dapsone did not show sufficient response rates to recommend their use. Authors note the risk of bias imposed by the type of evidence(case reports, case series) available in this field.CONCLUSION Dapsone is the recommended first line therapy for AATD panniculitis, followed by augmentation therapy. Plasma exchange may be an alternative in the setting of rapidly progressive disease.

Association of Vitamin D Deficiency with Diabetic Retinopathy in Young People with Type 1 Diabetes Mellitus

Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy. Univariate and multivariate logistic regression showed vitamin D deficiency was independently associated with diabetic retinopathy with a crude odds ratio of 5.69 with a p value of 0.008 and adjusted odds ratio of 16.08 with a p value of 0.002 respectively. Conclusion: Result of the study revealed that vitamin D deficiency was strongly associated with diabetic retinopathy in young people with type 1 diabetes mellitus.

Yiqi Huoxue Decoction in the treatment of Qi and yin deficiency and stasis type diabetic nephropathy in stageⅢ and its effect on VEGF and TGF-β1

Objective:To observe the efficacy of Yiqi Huoxue Decoction in the treatment of patients with diabetic nephropathy(DN)stageⅢwith qi and yin deficiency and stasis and its effects on vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β1).Methods:Sixty patients with stage DN of Qi-yin deficiency and stasis type DN who were treated in the Endocrinology Department of the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from September 2018 to December 2019 were selected as the research subjects.The remainder method was used to divide them into 30 cases in the observation group and 30 cases in the control group.Patients in both groups were referred to the guidelines and expert consensus for general treatment of DN(hypogl-ycemic,antihypertensive,lipid-lowering,etc.).The control group was given pancreatic kallikrein enteric-coated tablets orally once,120U,3 times a day,and the observation group was given The traditional Chinese medicine Yiqi Huoxue Decoction was taken orally,one dose daily,twice a day in the morning and evening;the two groups intervened continuously for 8 weeks.Detect blood FPG,PBG,HbA1c,β2-MG,BUN,SCr,VEGF,TGF-β1,and urine mALB and UACR levels before and after treatment,and calculate eGFR before and after treatment in both groups;observe changes in TCM syndrome scores in the two groups,Compare its clinical efficacy.Results:After 8 weeks of treatment,the total clinical effective rate of patients in the observation group was 93.3%,which was significantly different from the control group of 76.6%(P<0.05);the TCM syndrome scores in the observation group were significantly lower than those before treatment and in the control group(P<0.05);The levels of FPG,HbA1c,PPG,mALB,β2-MG,UACR,VEGF,and TGF-β1 in the observation group were significantly lower than those in the control group,with significant differences(P<0.05).The levels of SCr and BUN in the observation group were significantly lower.Compared with before treatment,eGFR increased,but there was no signi-ficant difference(P>0.05).Conclusion:Yiqi Huoxue Decoction for the treatment of patients with DN typeⅢqi-yin deficiency and stasis type,not only helps to lower blood sugar levels,improve TCM syndromes,but also can reduce early renal damage,reduce urine albumin,and delay kidney function It may be further worsened and has better safety.The mechanism may be related to reducing the levels of VEGF and TGF-β1,thereby delaying the fibrosis of tubulointerstitial scar and inhibi-ting glomerular capillary sclerosis.

Alpha-1 Antitrypsin Deficiency Family Study

According to the latest World Health Organization report 64 million people suffer from Chronic Obstructive Pulmonary Disease （COPD）, 3 million people died from COPD and it is predicted that COPD will become the third leading cause of death worldwide by 2030. The alpha-1 antitrypsin deficiency is a rarely diagnosed hereditary disease caused by a genetic mutation and it is one of the most prevalent genetic disorders primarily affecting the lungs, especially in the form of COPD or emphysema, but in some cases also the liver or skin. The Global Initiative for Chronic Obstructive Lung Disease recommends all patients with COPD at a young age or significant family history to be examined for alpha-1 antitrypsin deficiency. This article presents the case of a 42 year old, female patient, Portuguese, with history of Chronic Obstructive Pulmonary Disease, 40 pack units/year smoker, with unknown family history, coming to her family doctor with breath shortness, especially during physical activities, with unsatisfying response to pharmacological prescribed therapy. Physical examination was normal. Alpha- 1 antitrypsin deficiency was confirmed by blood testing. All patient＇s first degree relatives were investigated showing low alpha-1 antitrypsin blood concentrations thus genetic tests were later performed. This case reinforces the need for primary care physicians to be aware of alphal-antitrypsin deficit as an underdiagnosed clinical entity.

α_1-ANTITRYPSIN ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

Objective To investigate whether pretreatment with α 1-AT can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. Methods Thirty-two New Zealand rabbits were randomly assigned to four groups(n=8):1.Infusion of endotoxin(Lipopolysaccharide,LPS 500μg/kg)without α 1-AT (group LPS).2.Infusion α 1-AT 120mg/kg at 15min before challenge with LPS(group LAV).3.Infusion of α 1-AT 120mg/kg(group AAT).4 Infusion of saline 4ml/kg as control (group NS).Arterial blood gases,peripheral leukocyte counts and airway pressure were recorded every 1h.Physiologic intrapulmonary shunting (Qs/Qt) was measured every 4h.After 8h the bloods were collected for measurement of plasma concentration and activity of α 1-AT.Then bronchoalveolar lavage fluid (BALF)was collected for measurement of concentrations of total protein (TP),interleukin-8(IL-8),tumor necrosis factor(TNF-α),the activities of elastase-like and α 1-AT,total phospholipids(TPL) and disaturated phosphatidylcholine (DSPC).In addition,the wet-to-dry lung weight ratio(W/D) was measured. Results After infusion of endotoxin,it was observed that PaO 2,peripheral luekocyte counts,total respiratory compliance progressively decreased and P peak and Qs/Qt increased comparing with the baseline values.In contrast to group NS,the increased plasma concentration but reduced activity of α 1-AT was found in group LPS.In the BALF,the activity of α 1-AT,TPL,DSPC/TPL were lower,but the concentrations of albumin,IL-8,TNF-α,and the activity of NE were higher.The ratio of W/D also increased.The pretreatment of α 1-AT attenuated the deterioration of oxygenation,the reduction of compliance and the deterioration of other physiological,biochemical parameters mentioned above. Conclusion Pretreatment with α 1-AT could attenuate endotoxin-induced lung injury in rabbits.Those beneficial effects of α 1-AT might be due in part to the inhibitory effect on neutrophil elastase.

加味补阳还五汤对2型糖尿病周围神经病变气虚血瘀型患者血清FGF21、25(OH)D、ET-1水平及高凝状态的影响

【目的】探讨加味补阳还五汤治疗2型糖尿病周围神经病变气虚血瘀型患者的疗效及其对血清成纤维细胞生长因子21(FGF21)、25-羟维生素D[25(OH)D]、内皮素1(ET-1)水平和高凝状态的影响。【方法】将2019年12月至2022年12月海口市中医医院收治的124例2型糖尿病周围神经病变气虚血瘀型患者按随机数字表法随机分为对照组和观察组,每组各62例。对照组给予西医常规治疗,观察组在对照组的基础上联合加味补阳还五汤治疗,疗程为12周。观察2组患者治疗前后中医证候积分、血糖指标、血液流变学指标、神经传导速度及血清FGF21、25(OH)D、ET-1和白细胞介素6(IL-6)水平的变化情况,并评价2组患者的临床疗效。【结果】(1)疗效方面,治疗12周后,观察组的总有效率为96.77%(60/62),对照组为83.87%(52/62),组间比较(χ^(2)检验),观察组的疗效明显优于对照组(P<0.05)。(2)中医证候方面,治疗后,2组患者的肢体疼痛、感觉减退、多食易饥、肢体麻木等各项中医证候积分及总积分均较治疗前降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.05)。(3)血液流变学方面,治疗后,2组患者的血细胞比容、全血高切黏度、血浆黏度等各项血液流变学指标均较治疗前降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.05)。(4)神经传导速度方面,治疗后,2组患者的腓总神经和正中神经运动传导速度均较治疗前升高(P<0.05),且观察组的升高幅度均明显优于对照组(P<0.05)。(5)血糖指标方面,治疗后,2组患者的血清空腹血糖(FBG)、糖化血红蛋白(HbA1C)水平均较治疗前降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.05)。(6)血清FGF21、25(OH)D、ET-1、IL-6水平方面,治疗后,2组患者的血清FGF21、ET-1、IL-6水平均较治疗前降低(P<0.05),血清25(OH)D水平均较治疗前升高(P<0.05),且观察组对血清FGF21、ET-1、IL-6水平的降低幅度及对血清25(OH)D水平的升高幅度均明显优于对照组(P<0.05)。【结论】对于2型糖尿病周围神经病变气虚血瘀型患者,在西医常规治疗基础上联合加味补阳还五汤治疗,有助于减轻炎症反应,减轻血管内皮功能损伤,调节血糖水平,改善神经机能,提高临床疗效。

广州市汉族哮喘儿童α_1-抗糜蛋白酶杂合缺失分析

目的探讨α1 -抗糜蛋白酶 (α1-antichymotrypsin,α1-ACT )杂合缺失是否为广州市儿童哮喘发病的遗传机制以及地理环境是否影响α1-ACT杂合缺失在儿童哮喘中的分布。方法应用火箭免疫电泳技术对广州市50例哮喘儿童、50例健康儿童及100例健康成人血浆α1 -ACT含量进行检测 ;经家系调查确定3组α1-ACT杂合缺失频率 ;比较了哮喘组α1-ACT杂合缺失及非缺失患儿的临床资料。结果α1-ACT杂合缺失频率哮喘组、儿童对照组以及成人对照组依次为14 %、2 %、1 % ,哮喘组较儿童对照组明显增高 (χ2=4.891,P<0.05) ;广州市哮喘儿童α1-ACT杂合缺失频率 (14 % )明显高于重庆市哮喘儿童 (4.4 % ) ,χ2 =4.054,P<0.05 ;哮喘组α1 -ACT杂合缺失与非缺失患儿比较 ,前者哮喘住院次数多 ,放射性过敏原吸附试验阳性率显著增高。结论α1-ACT杂合缺失与儿童哮喘发病存在一定的联系 ;地理环境影响α1 -ACT杂合缺失频率分布。

益肾养阴固精方对2型糖尿病肾病气阴两虚证患者TGF-β1、S1P、NLRP3炎症小体及胰岛β细胞功能的影响

【目的】探讨益肾养阴固精方(左归丸化裁)在2型糖尿病肾病气阴两虚证治疗中的应用价值,观察其对炎症反应、胰岛β细胞功能及肾功能的影响。【方法】将2020年5月至2023年7月在陕西中医药大学附属医院就诊的162例2型糖尿病肾病气阴两虚证患者按随机数字表法随机分为观察组和对照组,每组各81例。对照组给予降压、护肾等西医常规治疗,观察组在对照组的基础上联合益肾养阴固精方治疗,疗程为12周。观察2组患者治疗前后中医证候总积分、胰岛素敏感指数、胰岛素分泌指数、24 h尿蛋白定量(24hUTP)及血清糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、空腹血糖(FBG)、血肌酐(SCr)、尿素氮(BUN)、转化生长因子β1(TGF-β1)、NLRP3炎症小体、白细胞介素6(IL-6)、超氧化物歧化酶(SOD)、1-磷酸鞘氨醇(S1P)水平的变化情况,并比较2组患者的临床疗效。【结果】(1)治疗12周后,观察组的总有效率为93.83%(76/81),对照组为83.95%(68/81),组间比较,观察组的疗效明显优于对照组(χ^(2)=9.163,P<0.05)。(2)治疗后,2组患者的胰岛素敏感指数、胰岛素分泌指数均较治疗前升高(P<0.05),中医证候总积分均较治疗前降低(P<0.05),且观察组对胰岛素敏感指数、胰岛素分泌指数的升高幅度及对中医证候总积分的降低幅度均明显优于对照组(P<0.05)。(3)治疗后,2组患者的血清HbA1c、FINS、FBG、SCr、BUN及24hUTP水平均较治疗前降低(P<0.05),且观察组对血清HbA1c、FINS、FBG、SCr、BUN及24hUTP水平的降低幅度均明显优于对照组(P<0.05)。(4)治疗后,2组患者的血清TGF-β1、IL-6、NLRP3炎症小体水平均较治疗前降低(P<0.05),血清S1P、SOD水平均较治疗前升高(P<0.05),且观察组对血清TGF-β1、IL-6、NLRP3炎症小体水平的降低幅度及对血清S1P、SOD水平的升高幅度均明显优于对照组(P<0.05)。【结论】对于2型糖尿病肾病气阴两虚证患者而言,联合益肾养阴固精方治疗有助于减轻炎症反应,改善胰岛β细胞功能,调节血糖水平,改善肾功能,提高临床疗效。