This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.
Female ; Animals ; Humans ; Mice ; Candidiasis, Vulvovaginal/drug therapy* ; Inflammasomes/genetics* ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; 1-Butanol/pharmacology* ; Fluconazole/therapeutic use* ; Interleukin 1 Receptor Antagonist Protein/therapeutic use* ; Mice, Inbred C57BL ; Candida albicans ; Cytokines ; Drugs, Chinese Herbal/pharmacology* ; Ethanol ; RNA, Messenger ; Calcium-Binding Proteins/therapeutic use*

Objective To explore the application value of automatic cytomorphological analyzer in the morphological analysis of white blood cells(WBC)in peripheral blood.Methods A total of 306 venous blood samples from inpatients and outpatients were randomly selected and prepared with automatic cytomorphological analyzer for WBC pre-classification.The differences between automatic cytomorphological analyzer counting,automatic blood cell analyzer counting and manual counting were compared,and the correlation between automatic cytomorphological analyzer and manual counting method was analyzed.Results Compared with the other two methods,the automatic cytomorphologi-cal analyzer was able to detect more types of WBC,especially abnormal cells.There were no signifi-cant differences between automatic cytomorphological analyzer and manual counting method for 6 ma-ture WBC types(band neutrophils,segmented neutrophils,lymphocytes,monocytes,eosinophils,and basophils),immature cells at different stages and atypical lymphocyte counts(P＞0.05).Re-sults of the 6 mature WBC types counted by the automatic cytomorphological analyzer and manual counting had favorable correlations(r＞0.8).Conclusion The automatic cytomorphological analyzer can classify more types of WBC,provide WBC counting results that are highly consistent with manual microscopy,and the counting results of the two methods have a good correlation.

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.
Humans ; Atrial Fibrillation/drug therapy* ; Cardiovascular Diseases ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Atherosclerosis ; Dyslipidemias/drug therapy*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34⁺ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34⁺ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.
Humans ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/complications* ; Prognosis ; Recurrence ; Retrospective Studies

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

OBJECTIVE: To observe the effect of acupuncture combined with infantile tuina on intestinal flora and its efficacy in children with tic disorders (TD), and to explore its mechanism. METHODS: A total of 15 children with TD were recruited as an observation group and 10 healthy children as a healthy control group. Regulating spleen and stomach acupuncture combined with infantile tuina were received in the observation group. First, acupuncture was applied to Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Hegu (LI 4), Zusanli (ST 36), etc., and then abdominal massage and other tuina techniques were applied, once a day, 6 times a week, 2 weeks as a course of treatment, a total of 2 courses of treatment were required. No intervention was given in the healthy control group. In the observation group, Yale global tic severity scale (YGTSS) score and TCM syndrome score were compared before treatment and after 1 and 2 courses of treatment. 16S rRNA sequencing technology was used to detect the intestinal flora in the healthy control group and before and after treatment in the observation group. RESULTS: After 1 and 2 courses of treatment, the scores of YGTSS and TCM syndrome in the observation group were lower than those before treatment (P<0.01, P<0.05). Compared with the healthy control group, the number of operational taxonomic units (OTU) and indexes of Chao1, Sobs, Ace and Shannon were decreased in the observation group before treatment (P<0.05, P<0.01). Compared with before treatment, the number of OTU and indexes of Chao1, Sobs, Ace and Shannon were increased in the observation group after treatment (P<0.01, P<0.05). Compared with the healthy control group, the relative abundance of Firmicutes in the observation group before treatment was decreased (P<0.001), while the relative abundance of Bacteroidetes, Bacteroides and Erysipelatoclostridium was increased (P<0.001, P<0.05). Compared with before treatment, the relative abundance of Bacteroidetes in the observation group was decreased (P<0.001) after treatment, while the relative abundance of Actinobacteria, Bifidobacterium and Atopobium was increased (P<0.05, P<0.01). CONCLUSION Acupuncture combined with infantile tuina based on the principle of regulating spleen and stomach could effectively improve TD symptoms in children, which may be related to regulating the diversity of intestinal flora, increasing beneficial bacteria, maintaining intestinal microecological balance, and playing a role in improving neurological disorders.
Child ; Humans ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Acupuncture Therapy ; Spleen ; Tic Disorders

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Gitelman syndrome(GS),also known as familial hypokalemia and hypomagnesemia,is a hypokalemic renal tubular disease caused by mutation in gene encoding the renal thiazide-sensitive sodium-chloride cotransporter(NCC),which is expressed in the distal convoluted tubule(DCT).GS is characterized by hypokalemic alkalosis and hypomagnesemia.At present,the main pathogenic genes of GS are SLC12A3 gene,KCNJ10 gene,HNF1B gene and so on.Gitelman-like syndrome has the same clinical manifestation as GS,but no classic gene mutation.It has not exactly the same pathogenic mechanism as GS.This paper summarizes the pathogenesis of Gitelman-like syndrome from genetic factors(mitochondrial gene variation,SLC26A4 gene mutation,BSND gene mutation,etc.)and non-genetic factors(diuretic abuse,aminoglycosamine antibiotics,cisplatin,etc.),in order to provide theoretical basis for further understanding,diagnosis and treatment of the disease.

Objective To explore the application value of automatic cytomorphological analyzer in the morphological analysis of white blood cells(WBC)in peripheral blood.Methods A total of 306 venous blood samples from inpatients and outpatients were randomly selected and prepared with automatic cytomorphological analyzer for WBC pre-classification.The differences between automatic cytomorphological analyzer counting,automatic blood cell analyzer counting and manual counting were compared,and the correlation between automatic cytomorphological analyzer and manual counting method was analyzed.Results Compared with the other two methods,the automatic cytomorphologi-cal analyzer was able to detect more types of WBC,especially abnormal cells.There were no signifi-cant differences between automatic cytomorphological analyzer and manual counting method for 6 ma-ture WBC types(band neutrophils,segmented neutrophils,lymphocytes,monocytes,eosinophils,and basophils),immature cells at different stages and atypical lymphocyte counts(P＞0.05).Re-sults of the 6 mature WBC types counted by the automatic cytomorphological analyzer and manual counting had favorable correlations(r＞0.8).Conclusion The automatic cytomorphological analyzer can classify more types of WBC,provide WBC counting results that are highly consistent with manual microscopy,and the counting results of the two methods have a good correlation.