ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

ObjectiveTo investigate the accuracy of multiple discriminant analysis （MDA） versus fibrosis-4 （FIB-4） in assessing liver fibrosis degree in patients with HBV infection， as well as the possibility of MDA as an indicator for disease progression. MethodsA total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included， and their clinical data were collected. According to the results of pathological examination， they were divided into non-significant fibrosis group （F<2） with 126 patients and significant fibrosis group （F≥2） with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed， and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up， and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit， they were divided into progressive group with 21 patients and non-progressive group with 41 patients； the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up， and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic （ROC） curve was used to investigate the diagnostic efficacy of indicators， the Z-test was used for comparison of the area under the ROC curve （AUC）， and the paired chi-square test was used for comparison of the sensitivity， specificity， and accuracy of the two indicators. ResultsThe correlation coefficient between FIB-4 and liver fibrosis degree was 0.378， while the correlation coefficient between MDA and liver fibrosis degree was -0.325 （both P<0.001）. FIB-4 had an AUC of 0.688， a sensitivity of 64.96%， a specificity of 68.87%， a positive predictive value of 67.42%， a negative predictive value of 63.36%， an accuracy of 65.40%， and a cut-off value of 1.01， while MDA had an AUC of 0.653， a sensitivity of 52.55%， a specificity of 78.57%， a positive predictive value of 72.73%， a negative predictive value of 60.37%， an accuracy of 65.02%， and a cut-off value of 0.29， suggesting that compared with FIB-4， MDA had a lower sensitivity （P=0.004） and a higher specificity （P=0.001）. The progressive group had a significantly higher age than the non-progressive group at baseline （t=2.611， P=0.011）. For the progressive group， there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up （both P<0.001）， while the non-progressive group showed no significant changes （both P>0.05）. The multivariate Logistic regression analysis showed that aspartate aminotransferase （odds ratio ［OR］=0.940， 95% confidence interval ［CI］： 0.885‍ ‍—‍ ‍0.998， P<0.05） and MDA （OR=0.445， 95%CI： 0.279‍ ‍—‍ ‍0.710， P<0.001） were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. ConclusionMDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis， and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis， which can help to reduce the need for liver biopsy in clinical practice.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN)，so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted，followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes，including visual analogue score (VAS)，patient health questionnaire-9 (PHQ-9)，and quality of life (QoL) scores were compared preoperatively，post-stage Ⅰ，and at 3，6，and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase，the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20，80%) chose the second-phase PNM implantation surgery，3 (3/20，15%) chose second-phase SNM implantation，and 1 (1/20，5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS，PHQ-9，and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3，6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation，the operation is simple and safe，and offers stable therapeutic effects.It is worthy of clinical promotion and application.

OBJECTIVE: To compare clinical effects of external fixation and minimally invasive percutaneous plate osteosynthesis (MIPPO) after external fixation in treating open fractures of tibial shaft. METHODS: From January 2020 to June 2022, 151 patients with open fracture of tibial shaft treated with external fixation stenting were divided into external fixation group and combined group according to different surgical methods. There were 81 patients in external fixation group, including 48 males and 33 females, aged from 21 to 68 years old with an average of (42.58±7.44) years old;according to Gustilo classification, 49 patients with typeⅡ, 32 patients with type ⅢA;the time from injury to treatment ranged from 2.5 to 10 h with an average of (4.25±0.74) h;external fixed stenting was performed. There were 70 patients in combined group, including 42 males and 28 females, aged from 20 to 69 years old with an average of (41.39±7.02) years old;35 patients with type Ⅱ and 35 patients with type ⅢA according to Gustilo classification;the time from injury to treatment ranged from 3 to 9 h with an average of (4.31±0.85) h;MIPPO treatment was performed after external fixed stenting. The time of callus formation, fracture healing and complications were compared between two groups. Rasmussen score and Hospital for Special Surgery (HSS) score were used to evaluate functional recovery of knee joint at 6 months after operation. RESULTS: Both groups were followed up for 6 to 13 months with an average of (10.17±2.33) months. The time of callus formation and fracture healing were (13.98±4.02) d and (70.26±12.15) d in combined group, and (18.56±4.37) d and (79.87±15.41) d in external fixation group, respectively. Combined group was better than external fixation group in the time of callus formation and fracture healing (P<0.05). At six months after operation, Rasmussen and HSS scores in combined group were (26.79±3.11) and (83.36±9.44), which were higher than those in external fixation group (24.51±4.63) and (79.63±8.46) (P<0.05). In external fixation group, there were 2 patients with incision infection, 2 patients with nail tract infection, 1 patient with stent loosening, fracture displacement, delayed union and malunion, and 1 patient with biocompatibility reaction in combined group, with statistical significance between two groups (P<0.05). CONCLUSION MIPPO could accelerate callus formation and fracture healing, improve knee function, improve clinical effects and reduce complications in patients with open tibial shaft fractures after external and external fixation.
Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Bone Plates ; External Fixators ; Fractures, Open/physiopathology* ; Stents ; Young Adult

OBJECTIVES: To study the clinical and genetic characteristics of children with congenital adrenal hyperplasia (CAH). METHODS: Clinical data, laboratory findings, and genetic test results of 63 children diagnosed with CAH at Henan Children's Hospital from January 2017 to December 2024 were retrospectively reviewed. RESULTS: Of the 63 patients, the mean age at the first visit was (21 ± 14) days; 29 (46%) were of male sex and 34 (54%) were of female sex. The predominant clinical manifestations were poor weight gain or weight loss (92%, 58/63), poor feeding (84%, 53/63), skin hyperpigmentation (83%, 52/63), and female external genital anomalies (100%, 34/34). Laboratory abnormalities included hyponatremia (87%, 55/63), hyperkalemia (68%, 43/63), metabolic acidosis (68%, 43/63), and markedly elevated 17-hydroxyprogesterone (92%, 58/63), testosterone (89%, 56/63), and adrenocorticotropic hormone (81%, 51/63). Among 49 patients who underwent genetic testing, CYP21A2 variants were identified in 90% (44/49), with c.293-13A/C>G (33%, 30/91) and large deletions/gene conversions (29%, 26/91) being the most frequent; STAR (8%, 4/49) and HSD3B2 (2%, 1/49) variants were also detected. Following hormone replacement therapy, electrolyte disturbances were corrected in 57 cases, with significant reductions in 17-hydroxyprogesterone, adrenocorticotropic hormone, and testosterone levels (P<0.001). CONCLUSIONS CAH presenting in neonates or young infants is characterized by electrolyte imbalance, external genital anomalies, and abnormal hormone levels. Genetic testing enables definitive subtype classification; in CYP21A2-related CAH, c.293-13A/C>G is a hotspot variant. These findings underscore the clinical value of genetic testing for early diagnosis and genetic counseling in CAH. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(11): 1367-1372.
Humans ; Adrenal Hyperplasia, Congenital/diagnosis* ; Male ; Female ; Retrospective Studies ; Infant ; Infant, Newborn

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis