OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11％)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74％)of the 47 PZ lesions,8(47.06％)of the 17 TZ le-sions,and 40(90.91％)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P＜0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8％,57.6％and 62.1％,and sensitivities of 57.2％,78.4％and 93.2％,respectively.The negative predictive values were 46.5％,85.7％and 79.2％,and the positive predictive values 76.2％,43.4％and 84.8％,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.

Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the β-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317-318 del/del), rs11467497 (163-166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.
Male ; Humans ; Asthenozoospermia/metabolism* ; Sperm Motility/genetics* ; Homozygote ; Polymorphism, Single Nucleotide ; Semen ; Sequence Deletion/genetics* ; Spermatozoa/metabolism* ; Nucleotides/metabolism* ; beta-Defensins/metabolism*

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

ObjectiveTo establish a chronic stress inducing depressive disorder mouse model via chemical genetics， that helps to optimize the animal modeling method of chronic stress-induced depressive disorder. MethodsTo continuously stimulate the rostral ventrolateral medulla （RVLM） of mouse by chemical genetic method to mimic the response to chronic stress. The changes about behavior， blood pressure and major inflammatory factors of the animal models were correspondingly observed. ResultsThe mouse model was established successfully. One hour after intraperitoneal administration of CNO， diastolic blood pressure and mean blood pressure were significantly increased in the model group compared with the control. After four weeks of continuous administration， the total distance of movement， the total entering bouts， the distance and duration of the central area in the model group were significantly decreased compared with the control in the open field experiment. The results of sucrose preference and rotarod experiment suggested anhedonia and weakened motor coordination ability in the model group. The heart rate， blood pressure， expressions of IFN-γ and IL-10 in the model group were higher than those in the control. ConclusionsOur model developed classic symptoms of depressive disorder efficiently and stably， as well as accompanying symptoms such as high blood pressure and mussy release of inflammatory factors. It provides a valuable scientific basis for improving the efficiency and stability of animal modeling of chronic stress-induced depressive disorder.

OBJECTIVE: To explore the clinical effect of bio lengthened stem arthroplasty replacement in the treatment of unstable intertrochanteric fractures in the elderly. METHODS: From January 2015 to January 2018, 64 elderly patients with unstable intertrochanteric fractures were analyzed retrospectively. According to the surgical treatment, patients were divided into arthroplasty replacement group (bio-lengthened stem arthroplasty replacement) and internal fixation group (PFNA). In the arthroplasty group, there were 34 cases, including 19 males and 15 females, with an average age of (81.32±3.81) years old. The Evans classification of fracture was type Ⅲ in 15 cases, type Ⅳ in 16 cases and type Ⅴ in 3 cases. In the internal fixation group, there were 30 cases, including 14 males and 16 females, with an average age of (79.90±3.61) years old. The Evans classification of fracture was type Ⅲ in 10 cases, type Ⅳ in 15 cases and type V in 5 cases. X ray and CT showed unstable intertrochanteric fracture of femur. The operation time, intraoperative blood loss and complications were observed. Harris hip function score and SF-36 life quality score were used to evaluate the clinical effect. RESULTS: All the incisions healed in stage Ⅰ. All patients were followed up for 13 to 39 months with an average of 23.4 months. The operation time and bleeding volume of the patients in the arthroplasty replacement group were more than those in the internal fixation group (<0.05). At the final follow-up, Harris function score of hip joint in the arthroplasty group was better than that in the internal fixation group (< 0.05);SF-36 life quality score in the arthroplasty group was better than that in the internal fixation group (<0.05). CONCLUSION The treatmentof unstable intertrochanteric fractures with bio-lengthened stem arthroplasty replacement and internal fixation can achieve good clinical results, but with bio-lengthened stem arthroplasty replacement, the postoperative complications are less, the function of hip joint is better, and the life quality and satisfaction of patients are higher.
Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Bone Nails ; Female ; Fracture Fixation, Internal ; Hip Fractures ; surgery ; Humans ; Male ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism. METHODS: Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium. RESULTS: Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment. CONCLUSIONS Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
Animals ; Blood Urea Nitrogen ; Cardiomegaly ; prevention & control ; Cardiomyopathies ; complications ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; Heart Ventricles ; Indican ; blood ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Nephrectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Objective To explore the relationship between interleukin (IL)-10 gene polymorphisms and the susceptibility or the outcomes of HCV infection among high-risk populations in Jiangsu province.Methods IL-10 gene SNPs were detected in 1555 subjects including 264 self-limited HCV infections.371 persistent HCV infections and 920 healthy controls were selected through Taqman-MGB.Results After adjusted for cofounders as sex,age and high-risk population,data from logistic regression analysis showed that the distribution of IL-10 genotypes among the controls,spontaneous clearances and those with persistent infections did not show much differences.Results from further stratified analysis showed that,at the position of-819T/C,when compared with TT genotype,TC genotype had a significantly increasing chance of self-limited HCV infection among middle-aged,females and paid blood doners (adjusted OR values and 95％ CI were:2.160,1.163 4.011 ；1.693,1.066-2.688 and 4.084,1.743-9.570).It also had a lower risk of progressing to persistent HCV infection among those paid blood doners (the adjusted OR values and 95％CI were:0.312,0.130-0.747 ).CC genotype had a higher chance of self-limited HCV infection among people underwent blood dialysis (the adjusted OR values and 95％CI were:2.120,1.071 -4.197).Results also showed a decreased risk of progressing to persistent infection among paid blood doners (the adjusted OR values and 95％CI were:0.156,0.043-0.566).At the position of -592A/C,when compared to AA genotypc,the AC genotype had a significantly increasing chance of self-limited HCV infection among middle-aged,femalcs and paid blood doners (the adjusted OR values and 95％ CI were:2.176,1.173-4.037；1.659,1.055-2.607;3.704,1.625-8.443) but had an increased risk of persistent HCV infection among females (the adjusted OR values and 95％CI were:1.525,1.017-2.286).AC genotype showed an increased opportunity to progress to HCV persistent infection among drug users (the adjusted OR values and 95％CI were:1.845,1.122-3.034) but had a reduced risk of progressing to HCV persistent infection among paid blood doners (the adjusted OR values and 95％CI were:0.361,0.155-0.841 ).CC genotype had an increased opportunity to self-linited HCV infection as well as having a dccreased risk of progressing to persistent infection among paid blood donets (the adjusted OR values and 95％CI were:3.125,1.016-9.605；0.218,0.063-0.748).At the position of-1082A/G,AG/GG genotypcs had an increased chance of self-limited infection among blood doners (the adjusted OR values and 95％CI were:3.780,1.620-8.820).Conclusion IL-10-819T/C,-592A/C,-1082A/G SNPs might be related with the susceptibility and the outcomes of HCV infection among populations at high risk.

Objective To introduce a novel technique of intracolonic shunt procedure used in the anus - preserving operation for acute intestinal obstruction resulted from cancer at low and middle portions of rectum and assess the clinical significance. Methods In total, 81 patients with acute obstruction of low and middle portion of rectum caused by cancer were randomly ( random number) divided into control group and study group. In control group, 42 patients were operated with preventive transverse colonostomy or terminal ileum stoma after low proximal resection of rectum involved in cancer, while 39 patients were operated with intracolonic shunt procedure by using a biodegradable anastomosis ring and a condom placed 5 cm above anastomosis for protection in study group. Results There were no significant differences in sex, age, tumor site, tumor size and the distance from anstomosis to anal-edge between two groups. In both groups, the bowel movement resumed in 2 ~ 5 days after operation (P > 0.05). In study group, the rate of anastomosis leakage was 7.7% (3/39), and leakages were treated with drainage for 7.1 days in average to be healed, and the biodegradable anastomosis ring detached and were discharged in 14 -23 days (17 days in average), and there were no complications of drainage happened. The anastomotic stenosis occurred in three patients (7. 7% ) within 6 months after operation. In control group, 11.9% patients (5/42) had anastomosis leakage and they treated with drainage for 18.2 days in average to get the leakage healed, and 35. 7% patients (15/42) had stoma complications, and anastomotic stenosis happened in 28.6% patients (12/42) within 6 months after operation, and 7. 1% patients need another operation because of severe anastomosis stenosis. There were no significant differences in rate of anastomosis leakage between tow groups ( P > 0. 05), but there were significant differences in drainage days after anstomosis leakage happened and 6 - months anastomosis stenosis between two groups (P<0.05). Conclusions In the anus -preserving operation for acute intestinal obstruction at low and middle portions of rectum caused by cancer , the intracolonic shunt procedure is convenient and safty, and reduces the hazard incurred by anastomosis leakage and anastomosis stenosis compared with classic stoma operation.