OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m²·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.
Humans ; Aged ; Azacitidine/therapeutic use* ; Prospective Studies ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols ; Leukemia, Myeloid, Acute/etiology* ; Proto-Oncogene Proteins c-bcl-2

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×10⁶ vs. 490 (210, 1 510)×10⁶/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.
Child ; Male ; Female ; Humans ; Infant ; Child, Preschool ; Retrospective Studies ; Respiratory Sounds ; Pneumonia, Mycoplasma ; Lung ; Respiratory Syncytial Virus Infections ; Mucus ; Pneumonia, Viral ; Risk Factors

ObjectiveTo investigate whether phosphodiesterase （PDE） 5 inhibitors sildenafil （SIL） or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction （UUO）. MethodsMale C57BL/6 mice were randomly divided into four groups （n =6）， namely the Sham group， 7UUO group， 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil （SIL） or LW1646， or vehicle was administered 1 hour before surgery， and the mice were continuously treated once daily （i. g.， 50 mg/kg） for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin （HE） and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis， apoptosis， endoplasmic reticulum （ER） stress， autophagy， and pro-fibrotic factors. Human proximal tubule epithelial cells （HK-2） were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours， respectively， to evaluate whether cyclic guanosine monophosphate （cGMP） or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7^th days after UUO， the body weight of the mice showed a significant decrease （P< 0.000 1） compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis， ER stress， autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice （P <0.05）. In contrast， SIL or LW1646 treatment was associated with attenuated tubular dilation， infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased， and the protein expression levels of apoptosis， endoplasmic reticulum stress， and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells， TGF-β1 induced increased expression levels of fibronectin and BiP， which was at least partially reversed by cGMP， a product of PDE inhibition. Additionally， PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion， PDE5 inhibitors， in particular， LW1646， can alleviate the progression of fibrosis by improving ER stress， apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

Humans ; Philadelphia Chromosome ; Neoplasms ; Myelodysplastic Syndromes/genetics* ; Disease Progression

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.
Animals ; Anti-Bacterial Agents/adverse effects* ; Diarrhea/drug therapy* ; Gastrointestinal Microbiome ; Ginger ; Plant Extracts ; Rats ; Rhizome

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.
Adrenocorticotropic Hormone ; China ; Cushing Syndrome/surgery* ; Female ; Gout ; Humans ; Hydrocortisone ; Iatrogenic Disease ; Male ; Skin, Artificial ; Wound Infection

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-κB/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1β（IL-1β） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（P<0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（P<0.05，P<0.01）. The uterine organ ratio were decreased significantly（P<0.01），while the ovarian organ ratio were significantly increased（P<0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（P<0.01）.The relative expression levels of inflammation-related protein IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein signaling pathway were significantly increased（P<0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（P<0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（P<0.05，P<0.01）. The uterine organ ratio were increased（P<0.05），while the ovarian organ ratio were decreased（P<0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（P<0.01）. The expression levels of IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein in the high dose group were significantly decreased（P<0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-κB/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．