Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.
Humans ; Bacterial Toxins/genetics* ; Enterotoxins/genetics* ; Clostridioides difficile/genetics* ; Multilocus Sequence Typing ; Coinfection ; Bacterial Proteins/genetics* ; China/epidemiology* ; Clostridium Infections/epidemiology* ; Diarrhea/microbiology*

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Child ; Cord Blood Stem Cell Transplantation ; Hematopoietic Stem Cell Transplantation ; Humans ; Primary Myelofibrosis/therapy* ; Thiotepa ; Transplantation Conditioning

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Angioplasty ; Angioplasty, Balloon ; Chronic Disease ; Humans ; Hypertension, Pulmonary ; Pulmonary Artery ; Pulmonary Embolism/complications* ; Thrombocythemia, Essential/complications*

Schistosomiasis is an important zoonotic parasitic disease, and is categorized as a neglected tropical disease by the World Health Organization. Following the concerted efforts for more than 70 years, great achievements have been made in the national schistosomiasis control program in China, and the prevalence, disability and mortality due to schistosomiasis has remarkably dropped. Nevertheless, the frequent identification of imported schistosomiasis and the resulting potential transmission risk in mainland China have been recently paid much attention following the implementation of the “Belt and Road Initiative” and the China-Africa Cooperation Forum. This review describes the advances in the diagnostic tools for schistosomiasis, including pathogenic techniques, immunodiagnostic techniques and nucleic acid assays, in order to consolidate schistosomiasis control achievements and promote the capability for detection of external biological safety risks.

Objective Serum total prostatic specific antigen (tPSA), free prostatic specific antigen (fPSA), fPSA/tPSA ratio, and prostate cancer-specific antigen density (PSAD) were determined to explore the best identification point, thus improving the specificity of early screening of prostate cancer. Methods The tPSA, fPSA, fPSA/tPSA, and PSAD of patients with benign prostatic hyperplasia group (n=250) and prostate cancer group (n=92) were tested, and the receiver operating characteristic (ROC) curve was drawn to determine the best cutoff value for the evaluation. Results When the cutoff values of tPSA, fPSA/tPSA, and PSAD were at 11.3 mg/L, 0.16, and 0.18 mg/(L·cm³), respectively, the specificity and sensitivity were the best:82.4% and 84.2% for tPSA, 76.9% and 81.7% for fPSA/tPSA, and 83.1% and 80.4% for PSAD.When the best cutoff values of tPSA, fPSA/tPSA, and PSAD were combined in analysis, the specificity and sensitivity of fPSA/tPSA and PSAD combination showed the best result (92.4% and 81.4%, respectively).When the tPSA value was in the range of 4-10 mg/L, the optimal cutoff values of PSAD and fPSA/tPSA were 0.21 mg/(L·cm³) and 0.15, and the specificity and sensitivity reach the best, which were 84.1% and 80.1%, 81.0 % and 80.3%, respectively. Conclusion Combination of tPSA, fPSA/tPSA and PSAD analysis is better than any single of them in early screening of prostate cancer.The specificity and sensitivity of combined use of fPSA/tPSA and PSAD could serve as an optimal screening reference value.