OBJECTIVE To investigate the effect of Huangqin decoction （HQD）-based self-assembled nanoparticles （SAN） co-loaded with terbinafine （TBF） （TBF-HQD-SAN NPs） on the transdermal absorption of TBF. METHODS High-speed centrifugation combined with dialysis was used to separate HQD-SAN， and TBF-HQD-SAN NPs were obtained by loading TBF using the ultrasound magnetic stirring method； the particle size distribution， Zeta potential and polydispersity index （PDI） of the nanoparticle were characterized， and the encapsulation efficiency （EE） and drug loading （DL） of TBF were determined； using in vitro and in vivo transdermal experiments， the differences in transdermal performance between TBF-HQD-SAN NPs and TBF raw materials， as well as TBF and HQD-SAN physical mixture （TBF-HQD-SAN PM）， were compared and analyzed. RESULTS TBF- HQD-SAN NPs were spherical with a particle size of （177.60±2.57） nm， a PDI of 0.197 4±0.007 9， and a Zeta potential of （－14.63±0.85） mV. The EE and DL of TBF were （99.49±0.71）% and （3.22±0.10）% ， respectively. In vitro transdermal experiments， compared with TBF raw materials， the steady-state permeation rate （Jss） and skin retention of TBF-HQD-SAN NPs increased by 3.34 times and 27.56 times， respectively （P＜0.05）； compared with TBF-HQD-SAN PM， its Jss and skinretention were increased by 2.04 times and 7.44 times， respectively （P＜0.05）. In vivo transdermal experiments 69号） showed that， the area under the drug-time curve and the maximum concentration of TBF-HQD-SAN NPs increased by 2.13 times and 2.06 times respectively compared to TBF raw materials， and increased by 1.59 times and 1.65 times respectively compared to TBF-HQD-SAN PM （P＜0.05）. CONCLUSIONS TBF-HQD-SAN NPs can significantly enhance the in vitro and in vivo transdermal absorption efficiency and skin retention of TBF.

Objective: To understand the epidemiological characteristics of a pertussis outbreak in Guangzhou, so as to provide references for outbreak response and prevention strategies. Methods: From April 5 to June 9, 2024, case screening was conducted among 246 preschool children, 35 staff members, and one full time school nurse in a kindergarten in Guangzhou based on case definition. Field epidemiological investigation methods were employed to collect relevant information, and screening samples were collected from individuals involved in the outbreak. The clinical manifestations, epidemiological characteristics, and risk factors for transmission of the outbreak were analyzed, with rate comparisons performed using the χ 2 test. Results: There were a total of 15 confirmed cases of pertussis in the kindergarten. The main clinical manifestations included intermittent cough in 14 cases ( 93.33 %), sputum production in 5 cases (33.33%), fever in 2 cases (13.33%), paroxysmal spasmodic cough in 1 case (6.67%), and vomiting in 1 case (6.67%). There was no statistically significant difference in the reporting rates of interrupted cough symptoms between pertussis cases (93.33%) and non pertussis cases (92.86%)( χ 2=3.74, P >0.05). The cases were aged 4-5 years, including 5 males and 10 females. The interval between symptom onset and diagnosis ranged from 2 to 25 days, with a median of 10 days. The outbreak involved two classes, with attack rates of 48.28% and 3.45%, respectively. Laboratory testing confirmed 14 close contacts positive for Bordetella pertussisnucleic acid. Among close contacts, only one received prophylactic medication as required. Conclusion The outbreak is a pertussis outbreak in a kindergarten caused by Bordetella pertussis infection, demonstrating distinct temporal and spatial clustering characteristics.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

Objective To report the diagnosis,treatment,and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent,and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders.Methods A 14-year-old patient presented with primary amenorrhea on April 3,2020,at the First Affiliated Hospital of Hebei North University,exhibiting female sexual characteristics.The patient underwent ultrasonic/magnetic resonance imaging of gonads,assessment of gonadal axis function,chromosomal karyotype,and molecular genetic testing,as well as pelvic exploration,malignant gonads resection,and hormone replacement therapy,resulting in drug-induced menstruation.During the diagnosis and treatment,it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results.Subsequently,samples from the three germ layer cells were taken,and fluorescence in situ hybridization(FISH)was used to detect the sex chromosomes in each germ layer cell.XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads,and changes in anti-Müllerian hormone(AMH)levels before and after surgery were compared.Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease.Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues.The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30%(6/20),in peripheral blood lymphocytes derived from the mesoderm was 9.7%(11/114),and in bladder shed cells derived from endoderm was 20.4%(22/108).The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome;where the epididymal structure area had a 45,X cell line mosaic of 50.0%,and the malignant area had a normal"Y"content.After gonadal resection,AMH levels significantly dropped from 7.28 pmol/L to＜0.07 pmol/L.Literature review revealed that patients with 45,X/46,XY have a complex phenotype spectrum,most with features of Turner syndrome,and female phenotypes are at risk of gonadal tumors.Conclusions In the diagnosis of difficult cases of sex development disorders,when performing peripheral blood karyotype testing,the number of counted cells and analyzed cells should be increased as much as possible,and multi-germ layer cell sampling should be performed.Gonads with a high"Y"mosaic rate are more prone to malignancy in the abdominal cavity.Detecting AMH levels can distinguish cryptorchidism and anorchidism in sexual development disorders with Y chromosomes.

This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Abelmoschus/chemistry* ; Macrophages/metabolism* ; Colitis, Ulcerative/immunology* ; Flavones/administration & dosage* ; Male ; Depression/genetics* ; Glycerophospholipids/metabolism* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

OBJECTIVES: To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor (MR) and the development of tubulointerstitial nephritis (TIN), and to evaluate the impact of MR on dyslipidemia, particularly secondary hyperlipemia, in patients with diabetic kidney disease. METHODS: We conducted a two-sample Mendelian randomization study using genome-wide association study (GWAS) summary data. Genetic variants associated with MR levels were selected as exposures, with TIN and lipid profiles [including low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol] as outcomes. A two-step Mendelian randomization approach was used to assess TIN as a mediator, employing inverse variance weighted regression as the primary analysis, supplemented by Mendelian randomization-Egger, weighted median, and sensitivity analyses. RESULTS: Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN (OR = 0.8598, 95% CI [0.7775-0.9508], P < 0.001). Although no significant causal relationship was identified between MR level and secondary hyperlipemia, a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed (OR = 0.9901, 95% CI [0.9821-0.9983], P = 0.018). Additionally, TIN exhibited causal links with secondary hyperlipemia (OR = 1.0016, 95% CI [1.0002-1.0029], P = 0.020) and elevated LDL-C (OR = 1.0111, 95% CI [1.0024-1.0199], P = 0.012), particularly LDL-C in European males (OR = 1.0230, 95% CI [1.0103-1.0358], P < 0.001). Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride (OR = 0.7027, 95% CI [0.6189-0.7978], P < 0.001), high-density lipoprotein cholesterol (OR = 1.1247, 95% CI [1.0019-1.2626], P = 0.046), and LDL-C (OR = 0.8423, 95% CI [0.7220-0.9827], P = 0.029). Notably, TIN mediated 16.7% of the causal association between MR and LDL-C levels. CONCLUSIONS MR plays a critical role in the development of TIN and lipid metabolism, highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.
Humans ; Mendelian Randomization Analysis ; Nephritis, Interstitial/metabolism* ; Receptors, Mineralocorticoid/genetics* ; Lipid Metabolism/genetics* ; Genome-Wide Association Study ; Male ; Female ; Polymorphism, Single Nucleotide ; Dyslipidemias/metabolism*

OBJECTIVE: To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (, YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy. METHODS: Fifty adult SD female rats were randomly divided into control group, sham group, model group, YSYSF group and positive drug group by using randomized numerical table method. In the model group, YSYSF group and positive drug group, polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group, the sham group and the model group were given equal amounts of saline by gavage, the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg^-1 once a day, and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg^-1 once a day. The motor function of the rats was assessed by the BBB method after 1, 3, 7, and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration, and the morphological changes of the spinal cord compression site were observed by HE staining, and the expression levels of Caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 were detected in the area of spinal cord injury by Western blot method. RESULTS: The BBB scores of the control group and the sham group were normal at all time points after modeling, which were higher than the BBB scores of the model group, the YSYSF, and the positive drug group (P<0.05). From the 3rd day after gavage, at all time points, the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group, and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths, whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001), and the expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05). CONCLUSION YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease, alleviate the pathological changes, and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD, the reduction of the release of inflammatory factors IL-1β and IL-18, the reduction of the expression of caspase-1 and GSDMD, the reduction of cellular death, and the inhibition of inflammatory response.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Spinal Cord/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Spinal Cord Diseases/drug therapy* ; Interleukin-1beta/metabolism*

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

This study aims to retrospectively analyze the distribution of human papillomavirus (HPV) subtypes and cervical lesion characteristics in female patients at Shenzhen Cancer Hospital. Adopting a retrospective observation research method. Using convenience sampling, the study subjects were selected from women who visited the Shenzhen Hospital of the Chinese Academy of Medical Sciences Cancer Hospital from September 2020 to December 2023.HPV genotyping was performed on cervical exfoliated cells from 6 402 women using rapid nucleic acid hybridization. Additionally, thinprep cytologic test (TCT) was conducted on 845 HPV-positive samples. High-grade squamous intraepithelial lesions (HSIL) were further classified as cervical intraepithelial neoplasia grades 2 or 3 (CIN2/3) through histopathological examination via cervical biopsy or conization. Data were statistically analyzed using χ2 test and two-sided test. The results showed that HPV testing identified 1 205 HPV-positive cases, with an overall positivity rate of 18.8% (1 205/6 402). Among these, the positivity rate for high-risk(HR) HPV was 14.34%(918/6 402), low-risk(LR) HPV was 3.58%(229/6 402), and other HPV types accounted for 0.91% (58/6 402). The most prevalent high-risk HPV subtypes were HPV16, HPV52, HPV39, HPV58, and HPV53, with positivity rates of 3.16% (202/6 402), 2.92% (187/6 402), 1.34% (86/6 402), 1.30%(83/6 402), and 1.05%(67/6 402), respectively. HPV16 had the highest infection rate in cervical malignancies, CIN3, and CIN2/3 groups, with rates of 53.18%(92/173), 47.37%(27/57), and 34.78%(8/23), respectively. Conversely, HPV52 showed the highest infection rate in the atypical squamous cells(ASC), Low-grade squamous intraepithelial lesion(LSIL), and CIN2 groups, at 29.68%(19/64), 23.50%(43/183), and 37.93%(11/29), respectively. Among 845 HPV positive female patients, the pathological diagnosis was squamous cell carcinoma, accounting for 22.13% (187/845), and adenocarcinoma accounting for 1.42%(12/845). HPV infection rates increased with age: 16.39%(97/592) in the ≤30 age group, 14.46%(301/2 082) in the 31-40 group, 17.26%(318/1 842) in the 41-50 group, 23.98%(300/1 251) in the 51-60 group, and 29.76%(189/635) in those over 60. In conclusion,in the female patient population of the Shenzhen Hospital of the Chinese Academy of Medical Sciences Cancer Hospital, HPV16 is associated with cervical cancer and high-grade cervical lesions, while HPV52 is related to low-to moderate-grade cervical lesions. Enhancing HPV screening among adult women is essential for preventing cervical cancer and associated lesions.