Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVES: To explore the risk factors of feeding intolerance (FI) in critically ill children receiving enteral nutrition (EN) and to construct a prediction nomogram model for FI. METHODS: A retrospective study was conducted to collect data from critically ill children admitted to the Pediatric Intensive Care Unit of Xiangya Hospital, Central South University, between January 2015 and October 2020. The children were randomly divided into a training set (346 cases) and a validation set (147 cases). The training set was further divided into a tolerance group (216 cases) and an intolerance group (130 cases). Multivariate logistic regression analysis was used to screen for risk factors for FI in critically ill children receiving EN. A nomogram was constructed using R language, which was then validated on the validation set. The model's discrimination, calibration, and clinical net benefit were evaluated using receiver operating characteristic curves, calibration curves, and decision curves. RESULTS: Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition were identified as independent risk factors for FI in critically ill children receiving EN (P<0.05). Based on these factors, a nomogram prediction model for FI in critically ill children receiving EN was developed. The area under the receiver operating characteristic curve for the training set and validation set was 0.934 (95%CI: 0.906-0.963) and 0.852 (95%CI: 0.787-0.917), respectively, indicating good discrimination of the model. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit (χ 2=12.559, P=0.128). Calibration curve and decision curve analyses suggested that the model has high predictive efficacy and clinical application value. CONCLUSIONS Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition are independent risk factors for FI in critically ill children receiving EN. The nomogram model developed based on these factors exhibits high predictive efficacy and clinical application value.
Humans ; Critical Illness ; Enteral Nutrition/adverse effects* ; Male ; Risk Factors ; Female ; Child, Preschool ; Infant ; Nomograms ; Retrospective Studies ; Child ; Logistic Models

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To explore the efficacy of using drug combination and sublingual immunotherapy（SLIT） for pediatric obstructive sleep apnea（OSA） and allergic rhinitis（AR） after adenotonsillectomy, in order to provide a more optimized treatment plan after the surgery. Methods:A total of 95 pediatric OSA combined with AR were selected. According to the treatment plan, they were divided into the SLIT group（postoperative medication combined with SLIT） and the control group（postoperative medication treatment only）. The comparisons were made between the two groups regarding the scores of the 18-item Quality of Life Questionnaire for Obstructive Sleep Apnea（OSA-18） and the Visual Analogue Scale（VAS） before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment; the monthly total medication scores（TMS） from 1 month to 3 months, 4 months to 6 months, 7 months to 1 year, and 1 year to 2 years after treatment, as well as the number of acute attacks of AR in the 1st year and 2nd year after treatment; and the Lund-Kennedy scores and nasal resistance grading of nasal endoscopy before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment. The effectiveness and safety were also analyzed. Results:After one year of treatment, the OSA-18 score, VAS score, TMS and Lund-Kennedy score in the SLIT group were significantly better than those in the control group. The nasal resistance was significantly reduced（P<0.05）, and the frequency of AR attacks was significantly lower than that in the control group（P<0.05）. After 2 years of treatment, the VAS score, Lund-Kennedy score and nasal resistance classification in the SLIT group tended to stabilize, while the OSA-18 score continued to decline. Conclusion:After surgery for pediatric OSA combined with AR, the use of drugs combined with SLIT can effectively alleviate AR symptoms, further improve OSA-related symptoms and quality of life, reduce drug dependence, decrease the frequency of AR attacks, and enhance the long-term efficacy of the surgery.
Humans ; Sleep Apnea, Obstructive/surgery* ; Rhinitis, Allergic/therapy* ; Quality of Life ; Child ; Tonsillectomy ; Treatment Outcome ; Adenoidectomy ; Sublingual Immunotherapy ; Drug Therapy, Combination ; Male ; Female

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

This study aimed to investigate the role and mechanism of sappanone A (SA) in regulating renal ischemia-reperfusion injury (IRI) in rats. The animal experiment has been approved by the Ethics Committee of Suzhou Wujiang District Children's Hospital (approval number: 2022010). First, hematoxylin-eosin (H&E) staining was used to evaluate the effects of SA on IRI, and renal damage was scored. Serum creatinine (SCr), blood urea nitrogen (BUN) and cystatin C (Cystatin C) were analyzed. The effect of sappanone A on the apoptosis of renal tubular epithelial cells induced by IRI was analyzed by TUNEL staining. Protein expression levels of p-JNK/JNK, p-ERK/ERK, Bcl2, Bax and cleaved-caspase 3 in renal tissues were detected by Western blot. Finally, H&E staining, serological analysis, TUNEL staining and Western blot were used to determine whether JNK activator anisomycin could reverse the effect of SA on IRI in rats. The results showed SA significantly reduced the renal tubule injury caused by ischemia-reperfusion, and decreased the level of SCr, BUN and Cys C in serum. TUNEL staining showed that SA significantly reduced the apoptosis of renal tubular epithelial cells induced by IRI. Western blot analysis of kidney tissue showed that SA significantly promoted the expression of apoptosis inhibiting protein Bcl2 and inhibited the expression of apoptosis-promoting proteins Bax and cleaved-caspase 3. Further analysis elucidated that SA did not affect the phosphorylation of ERK but decreased the phosphorylation of JNK. Finally, H&E staining, serological analysis, TUNEL staining and Western blot confirmed that JNK activator anisomycin could reverse the alleviating effect of SA on IRI in rats. The above findings suggest that SA could alleviate IRI in rats by inhibiting JNK phosphorylation.

BACKGROUND:Our previous experimental results have shown that hyaluronic acid hydrogel can act as a vehicle for bone marrow mesenchymal stem cell delivery to improve the cardiac function of rats with myocardial infarction. OBJECTIVE:To explore the molecular mechanism of bone marrow mesenchymal stem cells and hyaluronic acid hydrogel in promoting damaged heart repair. METHODS:Bone marrow mesenchymal stem cells from male Sprague-Dawley rats were isolated and cultured,and then hyaluronic acid-encapsulated bone marrow mesenchymal stem cells were cultured in vitro in a three-dimensional manner.A model of myocardial infarction was made by ligating the left anterior descending artery of female Sprague-Dawley rats.After 1 week,the model rats were screened by ultrasonic testing and then eligible ones were randomly divided into four groups:PBS group(n=12),hyaluronic acid group(n=12),bone marrow mesenchymal stem cell group(n=15),and hyaluronic acid-encapsulated bone marrow mesenchymal stem cell group(n=15).At 1 week after ligation,the model rats underwent the secondary thoracotomy followed by corresponding injections into the infarcted region and its marginal zone.The expression levels of matrix metalloproteinase-2,vascular endothelial growth factor,thymosin β4 and c-Kit were examined at post-injection day 1,week 1 and week 2 by western blot assay.At post-injection week 2,immunofluorescence staining was used to detect the differentiation of transplanted cells. RESULTS AND CONCLUSION:(1)The expression levels of matrix metalloproteinase-2 and vascular endothelial growth factor protein in the infarct zone in the bone marrow mesenchymal stem cell group were significantly up-regulated at week 1 compared with the other three groups(P<0.05).At week 2,the hyaluronic acid group had a lower expression of matrix metalloproteinase-2 and vascular endothelial growth factor protein than the other three groups(P<0.05).However,the expression of matrix metalloproteinase-2 and vascular endothelial growth factor protein in the hyaluronic acid+bone marrow mesenchymal stem cell group was not significantly different compared with the bone marrow mesenchymal stem cell group.This was primarily attributable to a prolonged paracrine effect via the controlled release of the hyaluronic acid hydrogel.This prolonged paracrine effect offsets the inhibitory effect induced by hyaluronic acid hydrogel at 2 weeks.(2)Compared with the PBS group,thymosin β4 and c-Kit expression levels in the hyaluronic acid group,bone marrow mesenchymal stem cell group and bone marrow mesenchymal stem cell+hyaluronic acid group were significantly increased(P<0.05).(3)No differentiation of transplanted cells into cardiomyocytes or blood vessels was detected 2 weeks after transplantation.(4)It is indicated that transplanted bone marrow mesenchymal stem cells promote myocardial repair through the paracrine effect,and hyaluronic acid hydrogel prolongs the paracrine effect of transplanted bone marrow mesenchymal stem cells.

The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.

Objective:To evaluate the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) for refractory glaucoma.Methods:A prospective multicenter observational case series study was conducted.A total of 63 refractory glaucoma patients (67 eyes) who underwent MP-TSCPC treatment were enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Chengdu First People's Hospital (Chengdu Integrated TCM& Western Medicine Hospital), and Changsha Aier Eye Hospital from August 2022 to April 2023.Among these cases, there were 40 eyes (59.7%) with unreduced intraocular pressure (IOP) after glaucoma surgery, 4 eyes (6.0%) with secondary glaucoma after vitrectomy, 2 eyes (3.0%) with secondary glaucoma after keratoplasty, 8 eyes (11.9%) with neovascular glaucoma, 3 eyes (4.5%) with secondary glaucoma due to iridocorneal endothelial syndrome, 6 eyes (9.0%) with primary open-angle glaucoma and 4 eyes (6.0%) with primary angle-closure glaucoma.Best corrected visual acuity (BCVA) was measured using the ETDRS chart and the IOP was measured using the Goldmann applanation tonometry before and 6 months after the surgery.The usage of anti-glaucoma medications before and after surgery and postoperative complications were recorded.Surgical success rate was calculated and surgical success was defined as an IOP reduction of more than 20% from baseline or a reduction in the number of ocular hypotensive medications with no change in IOP.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2022KYPJ225).Written informed consent was obtained from each subject.Results:There was a statistically significant overall difference in IOP at different time points before and after surgery ( F=60.10, P<0.001), and the IOP at different time points after surgery was significantly lower than that before surgery, with statistically significant differences (all at P<0.001).IOP reduction at 6 months after surgery was (43.7±20.7)%.The number of anti-glaucoma medications used postoperatively was 2(0, 3) types, which was significantly less than the 3(2, 3) types used preoperatively ( Z=-2.70, P=0.007).The 6-month postoperative BCVA (LogMAR) was 1.40(0.52, 2.70), which showed no significant change compared to the preoperative 1.40(0.70, 2.70) ( Z=-0.10, P=0.952).The surgical success rate was 83.6%(56/67) at 6 months postoperatively.Postoperative complications included mydriasis (11/67), conjunctival hemorrhage (11/67), mild anterior chamber inflammation (1/67), mild ciliary body detachment (3/67), local choroidal detachment (1/67), and cystoid macular edema (1/67), all of which were reversible after treatment. Conclusions:MP-TSCPC appears to be a safe and effective treatment option for refractory glaucoma.