ObjectiveTo investigate the possible mechanism of Pibai Yucuo Formula （枇柏愈痤方， PYF） in treating acne from the perspective of skin barrier damage. MethodsThirty-two mice were randomly divided into blank group， model group， minocycline group， and PYF group， with 8 mice in each group. Except for the blank group， mice were induced by intradermal injection of Cutibacterium acnes （C.acnes） combined with topical application of artificial sebum to establish acne model. The blank group and model group received intragastric administration of 0.2 ml of distilled water， while the PYF group received intragastric administration of 22.75 g/（kg·d）of PYF， and the minocycline group received 0.013 g/（kg·d）of minocycline suspension， all once daily for 5 consecutive days. On day 0 and day 6 of the experiment， the body weight of mice in each group was recorded， and the absolute value of the body weight difference during the experiment was calculated. Skin conditions were assessed with multifunctional skin imaging system on the 2nd， 4th and 6th day of the experiment. Skin barrier function indicators including transepidermal water loss （TEWL）， and the water content of the stratum corneum and epidermis on day 0， 2， 4 and 6 of the experiment. Optical coherence tomography （OCT） was used to observe stratum corneum and skin thickness on the 1st， 3rd and 5th day of the experiment. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes， while ELISA was used to detect interleukin-17A （IL-17A） levels， and immunofluorescence staining was used to assess skin barrier-related proteins filaggrin （FLG） and loricrin （LOR） levels of skin lesions on day 6 of the experiment. ResultsCompared to the blank group， the model group showed a decrease in body weight on day 6， and an increase in the absolute value of the difference in body weight before and after the experiment （P＜0.05）. On day 4 and 6， TEWL values increased， while water content in the skin stratum corneum and epidermis decreased （P＜0.05）， accompanied by elevated IL-17A level and reduced immunofluorescence intensity of FLG and LOR proteins （P＜0.05）. The model group mice showed papules or pustules at the skin modeling site with progressively worsening desquamation under multifunctional skin imaging system. OCT revealed focal epidermal protrusions， blurred epidermal-dermal boundaries， and disorganized structural layers. HE staining showed significant epidermal hyperkeratosis and incomplete keratinization in the skin， with keratin plug formation in hair follicles and glandular lumens， thickened stratum corneum， hyperplasia of the stratum spinosum， as well as dense dermal inflammatory cell infiltration， and capillary dilation. Compared to the model group， both the minocycline group and the PYF group showed a reduced difference in body weight before and after experiment （P＜0.05）. On day 4 and 6， the TEWL value decreased， and water content of the skin stratum corneum increased （P＜0.05）； on day 6， the IL-17A level in the skin lesions decreased and immunofluorescence intensity of FLG and LOR proteins increased （P＜0.05）. On day 4 and 6， the severity of the skin lesions and range of redness and swelling were lighter than those in the model group， with reverted epidermal thickness， smoother surface and clearer epidermis-dermis boundary. HE staining showed that the degree of skin keratinization was reduced， and the inflammatory infiltration and vascular dilation in the dermis were improved compared to the model group. The PYF group showed better results than the minocycline group in reducing TEWL value on day 4 （P＜0.05）. ConclusionPYF may improve inflammation and skin barrier damage by downregulating IL-17A levels in lesion tissue and increasing skin barrier-related proteins， which could be one of the potential mechanism of action on acne.

Objective:To explore the independent risk factors for predicting the right adrenal dominant secretory side in patients with primary hyperaldosteronism (PHA), so as to construct and verify the prediction model of the dominant secretory side, and provide evidence for the diagnosis and treatment of PHA patients.Methods:Clinical data of 82 PHA patients undergoing adrenal vein sampling (AVS) admitted to the Second Affiliated Hospital of Guangzhou Medical University from January 2015 to July 2023 were retrospectively analyzed, and divided into the training set (58 cases) and the verification set (24 cases) according to the ratio of 7∶3. Single factor and multiple factor logistic regression analysis were used to screen out the risk factors for predicting the right adrenal dominant secretory side, and then combined with the risk factors to build the prediction model of the dominant secretory side. The predictive efficiency and clinical applicability of the predominance secretory nomogram prediction model were verified by drawing receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA curve).Results:(1) Univariate and multivariate logistic analysis showed that the concentration of aldosterone (ALD2) in inferior vena cava and the results of adrenal CT imaging suggested that the right adrenal unilateral nodule (RJJ) were independent risk factors for the occurrence of right adrenal dominant secretion in PHA patients undergoing AVS (all P<0.05). (2) The area under ROC curve (AUC) corresponding to ALD2 variable was 0.898(95% CI: 0.735 7-0.986 1), and the sensitivity and specificity were 95.2% and 81.1%, respectively. The corresponding AUC of RJJ variable was 0.750(95% CI: 0.683 1-0.976 3), and the sensitivity and specificity were 90.5% and 86.7%, respectively. The AUC of the two variables in the verification set were 0.926 and 0.778, respectively. (3) Calibration curve and DCA curve showed that the prediction model had good consistency and clinical applicability, and can produce good clinical benefits. Conclusions:ALD2 and adrenal CT results suggest that RJJ is an independent risk factor for the prediction of the right adrenal dominant secretory side, and the prediction model based on these risk factors has good predictive efficacy and clinical applicability.

Objective:To investigate the application and effect of a competency-oriented teaching model in standardized nutritional diagnosis and treatment training for clinical physicians.Methods:A blended teaching method combining online and offline lectures was used to teach core knowledge and skills of clinical nutrition among clinical physicians by implementing a step-by-step "popularization-strengthening-deepening" strategy. The number of nutritional consultations, the improvement in nutritional diagnosis and treatment among clinical physicians, and the degree of satisfaction after training were used as assessment indices.Results:Compared with the data in 2021, the number of annual nutritional consultations was increased by 21.41% in 2022 and 53.18% in 2023. A total of 281 clinical physicians received online deepening course training, among whom 237 (84.34%) completed the online clinical nutrition knowledge test, with a mean score of (86.17±5.48) points and a pass rate of 81.86% (194/237). The online training received a satisfaction rate of 80.39%.Conclusions:The training program designed with competency-based objectives, systematic content, and diverse methodologies can significantly enhance the standardized thinking and capabilities of clinical physicians in nutritional diagnosis and treatment.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.

Objective:To explore the independent risk factors for predicting the right adrenal dominant secretory side in patients with primary hyperaldosteronism (PHA), so as to construct and verify the prediction model of the dominant secretory side, and provide evidence for the diagnosis and treatment of PHA patients.Methods:Clinical data of 82 PHA patients undergoing adrenal vein sampling (AVS) admitted to the Second Affiliated Hospital of Guangzhou Medical University from January 2015 to July 2023 were retrospectively analyzed, and divided into the training set (58 cases) and the verification set (24 cases) according to the ratio of 7∶3. Single factor and multiple factor logistic regression analysis were used to screen out the risk factors for predicting the right adrenal dominant secretory side, and then combined with the risk factors to build the prediction model of the dominant secretory side. The predictive efficiency and clinical applicability of the predominance secretory nomogram prediction model were verified by drawing receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA curve).Results:(1) Univariate and multivariate logistic analysis showed that the concentration of aldosterone (ALD2) in inferior vena cava and the results of adrenal CT imaging suggested that the right adrenal unilateral nodule (RJJ) were independent risk factors for the occurrence of right adrenal dominant secretion in PHA patients undergoing AVS (all P<0.05). (2) The area under ROC curve (AUC) corresponding to ALD2 variable was 0.898(95% CI: 0.735 7-0.986 1), and the sensitivity and specificity were 95.2% and 81.1%, respectively. The corresponding AUC of RJJ variable was 0.750(95% CI: 0.683 1-0.976 3), and the sensitivity and specificity were 90.5% and 86.7%, respectively. The AUC of the two variables in the verification set were 0.926 and 0.778, respectively. (3) Calibration curve and DCA curve showed that the prediction model had good consistency and clinical applicability, and can produce good clinical benefits. Conclusions:ALD2 and adrenal CT results suggest that RJJ is an independent risk factor for the prediction of the right adrenal dominant secretory side, and the prediction model based on these risk factors has good predictive efficacy and clinical applicability.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

Objective To investigate the clinical effect of percutaneous injection of calcitonin and methylprednone in the treatment of aneurysmal bone cyst in children.Methods From June 2020 to March 2023,19 patients with aneurysmal bone cysts were admitted and all were treated with percutaneous puncture injection of calcitonin and methylprednisolone.After percutaneous puncture biopsy,200 iu of calcitonin and 120 mg of methylprednone were injected into the cyst of aneurysmal bone cyst.Compare the volume of the cyst cavity and the thinnest cortical bone thickness around the cyst cavity before and after the operation.All patients were followed up,while preoperative and postoperative tumor cavity and the thinnest peritumor cortical thickness were compared.Results 19 patients were followed up for an average of 16 months(12-52 months).Of the 19 patients,17 were effective,the effective rate was 89.5％,and no serious complications occurred in all cases.At the last follow-up,the volume of the tumor cavity was significantly lower than that before surgery[(37.05±21.17)cm3,(110.95±45.67)cm3],and the difference was statistically significant(P＜0.05).The average thinnest cortical bone thickness around the tumor cavity was(0.71±0.37)mm before surgery and(1.87±0.60)mm after surgery.The difference was statistically significant(P＜0.05).Conclusion Percutaneous injection of calcitonin and methylprednone in the treatment of aneurysmal bone cysts in children is minimally invasive,safe and effective.It can be used as the first-line treatment for aneurysmal bone cyst in children.

Objective To investigate the clinical effect of percutaneous injection of calcitonin and methylprednone in the treatment of aneurysmal bone cyst in children.Methods From June 2020 to March 2023,19 patients with aneurysmal bone cysts were admitted and all were treated with percutaneous puncture injection of calcitonin and methylprednisolone.After percutaneous puncture biopsy,200 iu of calcitonin and 120 mg of methylprednone were injected into the cyst of aneurysmal bone cyst.Compare the volume of the cyst cavity and the thinnest cortical bone thickness around the cyst cavity before and after the operation.All patients were followed up,while preoperative and postoperative tumor cavity and the thinnest peritumor cortical thickness were compared.Results 19 patients were followed up for an average of 16 months(12-52 months).Of the 19 patients,17 were effective,the effective rate was 89.5％,and no serious complications occurred in all cases.At the last follow-up,the volume of the tumor cavity was significantly lower than that before surgery[(37.05±21.17)cm3,(110.95±45.67)cm3],and the difference was statistically significant(P＜0.05).The average thinnest cortical bone thickness around the tumor cavity was(0.71±0.37)mm before surgery and(1.87±0.60)mm after surgery.The difference was statistically significant(P＜0.05).Conclusion Percutaneous injection of calcitonin and methylprednone in the treatment of aneurysmal bone cysts in children is minimally invasive,safe and effective.It can be used as the first-line treatment for aneurysmal bone cyst in children.