Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

OBJECTIVE To optimize the stir-frying process of Platycodon grandiflorum， compare the protective effect of P. grandiflorum on lung injury in mice before and after stir-frying， and preliminarily explore the characteristics of “enhanced efficacy through processing” of stir-frying P. grandiflorum. METHODS On the basis of single-factor experiment， the stir-frying time， temperature and frequency were taken as factors， and the comprehensive scores of appearance traits， platycodin D content and alcohol extract content were taken as indexes. Box-Behnken response surface experiment was designed to optimize the stir-frying process of P. grandiflorum and verify it. The mice were divided into blank control group， model group， dexamethasone group （positive control drug， 5 mg/kg）， P. grandiflorum low-dose and high-dose groups （0.6，1.2 g/kg）， fried P. grandiflorum low and high dose groups （0.6， 1.2 g/kg）， with 8 mice in each group. The treatment was given once a day for 10 consecutive days. After the last administration， acute lung injury model was established by intratracheal instillation of lipopolysaccharide. The levels of interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α） in serum and superoxide dismutase （SOD）， myeloperoxidase （MPO） and malondialdehyde （MDA） in lung tissue were detected， lung wet/dry weight ratio and thymus index were calculated， and the pathological changes of lung tissue were observed. RESULTS The optimum processing conditions were as follows：stir- frying temperature of 120 ℃， stir-frying time of 12 min， stir-frying frequency of 19 r/min； the comprehensive scores of the three batches of process verification were all greater than 97 points， RSD＜3% （n＝3）. The results of pharmacodynamic experiments showed that compared with blank control group， the lung dry-wet weight ratio as well as the levels of IL-6， IL-1β， TNF-α， MPO and MDA in the model group were significantly increased （P＜0.01）， the thymus index and SOD level were significantly decreased （P＜0.01）， and the lung tissue was significantly damaged. Compared with model group， above indexes of the mice in each administration group were significantly improved （P＜0.01）， and the lung tissue injury was significantly reduced. At the same dose， except for the lung dry-wet weight ratio， the above indexes of the mice in the stir-fried P. grandiflorum groups were significantly improved compared with P. grandiflorum 涵。E-mail：495758271@qq.com groups （P＜0.05）， and the lung tissue damage was further reduced. CONCLUSIONS The optimized stir-frying process is stable and feasible. The protective effect of stir-fried P.grandiflorum on acute lung injury in mice is better than that of raw products at the same dosage.

Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

This study investigated the primary pathogenesis and syndrome evolution of different heart failure with preserved ejection fraction(HFpEF)stages based on the classical and clinical experience of traditional Chinese medicine(TCM),combined with the clinical characteristics of pre-heart failure,symptomatic heart failure,and advanced heart failure.This study summarizes and refines the three core syndrome factors:water,deficiency and blood stasis.Water-fluid retention was observed throughout these three stages,from the beginning to the end.With the advancement of the disease,the heart yang changes from stagnation to deficiency,water-fluid retention gradually increases,blood stasis becomes increasingly prominent,and the disease location develops dynamically from the upper to the middle and lower jiao.This study proposes three methods of treating HFpEF.The main pathogenesis of pre-heart failure is lung qi dysfunction-induced water retention,which can be treated by dispersing lung qi and transforming water retention using Fuling Xingren Gancao Decoction.The primary pathogenesis of symptomatic heart failure is yang and qi deficiency-induced water retention,which can be treated with tonifying yang,supplementing qi,and transforming water retention using Shengxian Decoction combined with Linggui Zhugan Decoction.The primary pathogenesis of advanced heart failure is yang deficiency with blood stasis and water retention affecting the heart,which can be treated with tonifying yang,circulating blood,and expelling water retention using Zhenwu Tingli Decoction.Chinese medicine can be flexibly added or subtracted according to the patients'concurrent patterns.However,the daily care of patients should be considered.This study explores the staging treatment of HFpEF from water,deficiency and blood stasis to provide a TCM clinical reference for treating HFpEF.

Objective To compare the short-term efficacy and safety of inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE) and minimally invasive transthoracic esophagectomy (MITE) in the treatment of esophageal cancer. Methods The Cochrane Library, EMbase, PubMed, Wanfang Database, VIP, and CNKI were searched. Literatures related to the short-term efficacy and safety of IVMTE and MITE in the treatment of esophageal neoplasms published from the establishment of the database to December 2023 were searched and meta-analysis was conducted by using RevMan5.4. Quality of case control study or cohort study was assessed by the Newcastle-Ottawa Scale (NOS) and quality of randomized controlled trial was assessed by Cochrane Handbook. Results A total of 14 studies (12 case control studies and 1 prospective cohort study wiht NOS score more than 7 points and 1 randomized controlled trial wiht low bias risk) were included, comprising 1 163 patients, with 525 in the IVMTE group and 638 in the MITE group. The results of meta-analysis revealed that the IVMTE group exhibited significantly shorter operative time [MD=−60.42, 95%CI (−83.78, −37.07), P<0.001] and postoperative hospital stay [MD=−2.44, 95%CI (−2.93, −1.94), P<0.01] compared to the MITE group. Moreover, intraoperative blood loss [MD=−34.67, 95%CI (−59.11, −10.23), P=0.005], three-day postoperative drainage [MD=−286.66, 95%CI (−469.93, −103.40), P=0.002], incidence of postoperative pulmonary infection [OR=0.38, 95%CI (0.26, 0.56), P<0.001], lung leakage rate [OR=0.12, 95% CI (0.02, 0.63), P=0.01] and overall complication rate [MD=0.41, 95%CI (0.22, 0.75), P=0.004] were all lower in the IVMTE group compared to those in the MITE group. However, the MITE technique demonstrated superiority over IVMTE regarding intraoperative lymph dissection number [MD=−3.52, 95%CI (−6.36, –0.68), P=0.02] and intraoperative recurrent laryngeal nerve injury [OR=1.78, 95%CI (1.22, 2.60), P=0.003]. No significant difference was observed between both methods concerning anastomotic fistula. Conclusion Compared to MITE, IVMTE has advantages such as shorter operation time, less intraoperative blood loss, shorter hospital stay, less postoperative drainage within 3 days, and a lower incidence of pulmonary complications. In terms of laryngeal recurrent nerve injury and lymphatic dissection, MITE operation offers more benefits.

Objective To systematically evaluate the efficacy of adjuvant radiotherapy after thymoma resection. Methods The PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang, VIP, CNKI databases were systematically searched to find relevant literature comparing the efficacy and effectiveness of thymoma resection and thymoma resection+postoperative radiation therapy (PORT) for treating thymoma published from inception to January 2024. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included retrospective studies, and Review Manager 5.4 software was used to perform meta-analysis. Results A total of 23 articles were included, all of which were retrospective studies. There were a total of 13742 patients, including 6980 patients in the simple surgery group, with 3321 males and 3659 females, and an average age of 54.08 years; 6762 patients in the surgery+PORT group, with 3385 males and 3377 females, and an average age of 53.76 years. The NOS scores of the included literature were all≥7 points. The results of the meta-analysis showed that compared with the simple surgery group, the surgery+PORT group had higher 1-year overall survival rate [OR=0.32, 95%CI (0.25, 0.42), P<0.001], 3-year overall survival rate [OR=0.55, 95%CI (0.48, 0.64), P<0.001], 5-year overall survival rate [OR=0.66, 95%CI (0.58, 0.75), P<0.001], 10-year overall survival rate [OR=0.71, 95%CI (0.57, 0.88), P=0.002], 1-year disease-free survival rate [OR=0.47, 95%CI (0.23, 0.93), P=0.030], 5-year disease-free survival rate [OR=0.61, 95%CI (0.45, 0.84), P=0.003], 3-year disease-specific survival rate [OR=0.44, 95%CI (0.35, 0.55), P<0.001], 5-year disease-specific survival rate [OR=0.53, 95%CI (0.44, 0.63), P<0.001] and 10-year disease-specific survival rate [OR=0.53, 95%CI (0.35, 0.82), P=0.004]. But there was no statistically significant difference between the two groups in terms of 3-year disease-free survival rate [OR=0.86, 95%CI (0.61, 1.22), P=0.400], 10-year disease-free survival rate [OR=0.70, 95%CI (0.47, 1.05), P=0.080] and 1-year disease-specific survival rate [OR=0.83, 95%CI (0.55, 1.26), P=0.380]. Conclusion PORT after thymoma resection has more advantages than simple surgical treatment in terms of 1-, 3-, 5-, and 10-year overall survival, 1- and 5-year disease-free survival, and 3-, 5- and 10-year disease-specific survival.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.