ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

The number of patients with reduced blood volume due to haemorrhage, fractures, severe infections, extensive burns and tumours is increasing, and traditional blood products are no longer able to meet the increasing clinical demand. Therefore, plasma substitutes have become particularly important in fluid resuscitation, especially artificial colloidal solutions, which have a sustained volume expansion time and a good volume expansion effect, and can significantly improve the circulatory status of patients. This article aims to review the classification of artificial colloidal plasma substitutes and their research progress in clinical practice, in order provide a more rigorous, professional and standardized reference for medicine.

OBJECTIVE: To re-analyze a likely pathogenic variant in the Xq28 region identified by copy number variation sequencing (CNV-seq) through whole genome sequencing (WGS). METHODS: A fetus found to harbor a duplication in the Xq28 region by CNV-seq at Shengjing Hospital Affiliated to China Medical University in May 2023 was selected as the study subject. WGS was carried out for the fetus and its parents. Bioinformatic software was used to analyze the chromosomal structure and CNVs. Quantitative PCR (qPCR) was applied to determine the expression level of the MECP2 gene. This study has been approved by the Ethics Committee of Shengjing Hospital (Ethic No. 2013PS33K). RESULTS: A duplication (ChrX:153302641_153503563) and four breakpoints were identified on the X chromosome of the fetus' father. Bioinformatic analysis revealed that the duplicated region has involved exons 1 to 3 and part of the 5'-UTR of the MECP2 gene, which was inserted into the Xp11 region. Additionally, an inversion was detected in the Xp11 region adjacent to the duplicated segment. RT-PCR results showed normal level of MECP2 mRNA expression. The Xq28 duplication has not encompassed the entire MECP2 gene, nor disrupted its structure or altered its expression. CONCLUSION WGS has enabled more precise diagnosis of chromosomal structural variants and provided guidance for accurate genetic counseling for the affected families.
Humans ; Female ; Chromosomes, Human, X/genetics* ; DNA Copy Number Variations/genetics* ; Whole Genome Sequencing/methods* ; Methyl-CpG-Binding Protein 2/genetics* ; Pregnancy ; Male ; Adult

Objective:To re-analyze a likely pathogenic variant in the Xq28 region identified by copy number variation sequencing (CNV-seq) through whole genome sequencing (WGS).Methods:A fetus found to harbor a duplication in the Xq28 region by CNV-seq at Shengjing Hospital Affiliated to China Medical University in May 2023 was selected as the study subject. WGS was carried out for the fetus and its father. Bioinformatic software was used to analyze the chromosomal structure and CNVs. Quantitative PCR (qPCR) was applied to determine the expression level of the MECP2 gene. This study has been approved by the Ethics Committee of Shengjing Hospital (Ethic No. 2013PS33K). Results:A duplication (ChrX: 153302641_153503563) and four breakpoints were identified on the X chromosome of the fetus′ father. Bioinformatic analysis revealed that the duplicated region has involved exons 1 to 3 and part of the 5′-UTR of the MECP2 gene, which was inserted into the Xp11 region. Additionally, an inversion was detected in the Xp11 region adjacent to the duplicated segment. RT-PCR results showed normal level of MECP2 mRNA expression. The Xq28 duplication has not encompassed the entire MECP2 gene, nor disrupted its structure or altered its expression. Conclusion:WGS has enabled more precise diagnosis of chromosomal structural variants and provided guidance for accurate genetic counseling for the affected families.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.