OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective:To analyze the clinical efficacy of electrolysis of depigmented hair using a trichiasis electrolyzer combined with hair follicle transplantation in the treatment of vitiligo-associated leukotrichia.Methods:Clinical data were retrospectively collected from 25 patients with stable vitiligo-associated leukotrichia in the Department of Dermatologic Surgery, Hangzhou Third People′s Hospital from January 2019 to January 2021. All the patients received electrolysis of depigmented hair using a trichiasis electrolyzer combined with hair follicle transplantation. Outpatient follow-up visits were conducted in the first week, as well as the first, third and sixth months after surgery. The texture and growth status of transplanted hair were observed, and the survival rate of transplanted hair follicles and the proportion of newborn white hair in white hair in the original lesions were recorded.Results:Among the 25 patients with stable vitiligo, there were 14 males and 11 females, and their disease duration ranged from 2 to 15 years, with the average duration being 5.8 years. A total of 30 white patches accompanied by leukotrichia were included, including 9 on the scalp, 7 on the eyebrows and 14 on the eyelashes. One week after surgery, the transplanted hair survived well in all patients, without obvious shedding or local infection. Six months after surgery, repigmentation was observed in most hair in the original lesion area, and only a small amount of white hair grew out, without obvious scarring; the survival rate of transplanted hair follicles was 76.5% ± 10.0%, and the proportion of newborn white hair in white hair in the original lesions was 16.7% ± 7.8%.Conclusion:Electrolysis of depigmented hair using a trichiasis electrolyzer combined with hair follicle transplantation was effective in the treatment of vitiligo-associated leukotrichia, with a simple treatment process and few postoperative complications, which provided a reliable choice for the clinical treatment of vitiligo-associated leukotrichia.

Objective To compare the differences in the clinical application of Sijunzi Decoction,a classical formula for tonifying qi,in ancient and modern literature,so as to provide a reference for its clinical application and research and development.Methods The clinical application of Sijunzi Decoction in ancient times was analyzed by retrieving the database of Zhong Hua Yi Dian(Collection of Traditional Chinese Medical Books),and the clinical application of Sijunzi Decoction in modern times was analyzed by retrieving the database of China National Knowledge Infrastructure(CNKI).Results In the record of ancient traditional Chinese medicine books,Sijunzi Decoction was indicated for the syndromes characterized by the pathogenesis of"deficiency of nutrient qi and defensive qi,and weakness of zang-fu organs",and was widely used to treat various diseases related to internal medicine,surgery,gynecology and pediatrics,including dysentery,consumptive disease,diarrhea,jaundice,smallpox,metrorrhagia and carbuncle.Moreover,Sijunzi Decoction was used for the management of patients who was weakness due to chronic diseases,elderly and insufficiency of qi,or at the late stage of exogenous cold disease,cholera,and malaria.In the modern clinical practice,Sijunzi Decoction was indicated for digestive system diseases,surgical diseases,tumor-related diseases,pediatric diseases,gynecological diseases,respiratory diseases and hepatobiliary diseases,in particular for chronic gastritis,adverse reactions related to radiotherapy and chemotherapy for tumors,postoperative period of cancer and diabetes mellitus during pregnancy.Conclusion The analysis of ancient and modern literatures indicated that the indications of Sijunzi Decoction is expanded from the predominated spleen-stomach system diseases(digestive system diseases)in antient times to multiple system diseases such as surgical diseases,tumor-related diseases,pediatric diseases,gynecological diseases,respiratory diseases and hepatobiliary diseases in modern times.And the pathogenesis of the indications of Sijunzi Decoction is characterized by the"deficiency of nutrient qi and defensive qi,and weakness of the zang-fu organs".

Background: Cerebral vasospasm has been reported following various forms of bacterial meningitis; however, there have been no prior reports of meningitis caused by the non-K1 strain of Escherichia coli. Case Report: A 63-year-old man with chronic thrombocytopenia presented with new-onset seizures that progressed to coma. Cerebrospinal fluid (CSF) analysis showed Gram-negative rods, but CSF culture and the Biofire FilmArray Meningitis/Encephalitis Panel were negative. Additional 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction and sequencing of the CSF sample indicated E. coli meningitis when correlated with the results of urine culture. The patient eventually developed diffuse cerebral arterial vasospasms with multifocal brain infarcts that progressed to brain death. Conclusion E. coli meningitis in adults may be missed if diagnostic tests include only K1 strains. Clinicians should be aware of cerebral vasospasm as a potentially serious complication of E. coli meningitis, and should consider screening for it, particularly in patients with associated risk factors.

Background: Cerebral vasospasm has been reported following various forms of bacterial meningitis; however, there have been no prior reports of meningitis caused by the non-K1 strain of Escherichia coli. Case Report: A 63-year-old man with chronic thrombocytopenia presented with new-onset seizures that progressed to coma. Cerebrospinal fluid (CSF) analysis showed Gram-negative rods, but CSF culture and the Biofire FilmArray Meningitis/Encephalitis Panel were negative. Additional 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction and sequencing of the CSF sample indicated E. coli meningitis when correlated with the results of urine culture. The patient eventually developed diffuse cerebral arterial vasospasms with multifocal brain infarcts that progressed to brain death. Conclusion E. coli meningitis in adults may be missed if diagnostic tests include only K1 strains. Clinicians should be aware of cerebral vasospasm as a potentially serious complication of E. coli meningitis, and should consider screening for it, particularly in patients with associated risk factors.

Background: Cerebral vasospasm has been reported following various forms of bacterial meningitis; however, there have been no prior reports of meningitis caused by the non-K1 strain of Escherichia coli. Case Report: A 63-year-old man with chronic thrombocytopenia presented with new-onset seizures that progressed to coma. Cerebrospinal fluid (CSF) analysis showed Gram-negative rods, but CSF culture and the Biofire FilmArray Meningitis/Encephalitis Panel were negative. Additional 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction and sequencing of the CSF sample indicated E. coli meningitis when correlated with the results of urine culture. The patient eventually developed diffuse cerebral arterial vasospasms with multifocal brain infarcts that progressed to brain death. Conclusion E. coli meningitis in adults may be missed if diagnostic tests include only K1 strains. Clinicians should be aware of cerebral vasospasm as a potentially serious complication of E. coli meningitis, and should consider screening for it, particularly in patients with associated risk factors.

Objective:To evaluate the effect of intrathecal exosomes derived from human amniotic fluid (hAF exo) on neuropathic pain induced by spared nerve injury (SNI) in mice.Methods:Eighteen clean-grade healthy male Kunming mice, aged 7-8 weeks, weighing 30-35 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SNI group, and SNI+ hAF exo group. Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized mice. Another three mice were selected to develop the model of neuropathic pain after anesthesia. PKH-26 labeled hAF exo 7 μl was intrathecally injected on days 1, 2 and 3 after developing the model. The mice were sacrificed at 10 h after the end of administration, and the uptake of hAF exo by the dorsal horn of the injured lumbar enlargement of the spinal cord was observed with the fluorescence microscope. On 1, 2 and 3 days after developing the model, 1 μg/μl hAF exo 7 μl was intrathecally injected in SNI+ hAF exo group, and PBS 7 μl was intrathecally injected in Sham group and SNI group. The mechanical paw withdrawal threshold (MPWT) was measured at 1 day before and 1, 3, 5 and 7 days after operation. And then the mice were sacrificed after measurement of the pain threshold at 7 days after developing the model, and the ipsilateral lumbar enlargement of the spinal cord was taken for determination of the expression of CD11b, interleukin-1beta (IL-1β) and IL-10 by Western blot. Results:The dorsal horn of the lumbar enlargement of the spinal cord on the injured side could absorb hAF exo with the fluorescence microscope. Compared with Sham group, the MPWT was significantly decreased at 3-7 days after developing the model, the expression of CD11b and IL-1β was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10 in SNI group ( P>0.05). Compared with SNI group, the MPWT was significantly increased at 3-7 days after developing the model, the expression of CD11b and IL-1β was down-regulated, and the expression of IL-10 was up-regulated in SNI+ hAF exo group ( P<0.05). Conclusions:Intrathecal exosomes derived from human amniotic fluid can alleviate neuropathic pain in mice, and the mechanism may be related to mediation of the polarization of microglia from M1 type to M2 type and attenuation of neuroinflammation.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.
Child ; Humans ; Adult ; Lymphohistiocytosis, Hemophagocytic/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning/methods*

Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.
Animals ; Mice ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor ; Apoptosis/genetics* ; bcl-2-Associated X Protein ; Caspase 3 ; Cognition ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondrial Dynamics/genetics*

Objective To establish an efficient method for isolating migrasomes from RAW264.7 macrophages and identifying these isolated migrasomes. Methods Scanning electron microscopy was used to observe the morphological characteristics of migrasomes produced by RAW264.7 cells. A 0.45 μm filter was employed for reverse filtration and elution to isolate the migrasomes. The morphological characteristics of the migrasomes were then observed using transmission electron microscopy. Western blot analysis was performed to determine the expression of characteristic markers of the migrasomes. The RNA carried by the migrasomes was analysed by using LabChip bioanalyzer. Results Scanning electron microscopy revealed that the migrasomes, with membranous structures, were attached to the tip or bifurcation of the retraction fiber formed in the tail of RAW264.7 cells. Transmission electron microscopy showed that the isolated migrasomes had a typical oval vesicle-like structure with wrinkled membrane surfaces. Western blot analysis confirmed the expression of the characteristic markers phosphatidylinositol glycan anchor biosynthesis class K (PIGK), epidermal growth factor domain-specific O-linked N-acetylglucosamine transferase (EOGT) and tetraspanin 4 (TSPAN4) in the migrasomes, while the EV (extracellular vesicle) markers tumor susceptibility gene 101 (TSG101) and Arabidopsis homolog of apoptosis-linked gene 2-interacting protein X (ALIX) were not detected. Furthermore, the isolated migrasomes were found to be rich in small RNA, which were approximately 25-200 nt in length. Conclusion A method for the extraction of well-structured and high quality migrasomes from macrophages is established.
Extracellular Vesicles ; Microscopy, Electron, Transmission ; RNA ; Macrophages