Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

ObjectiveTo explore the risk factors for liver injury in sepsis， so as to provide a reference for the diagnosis and treatment of sepsis patients with liver injury. MethodsA retrospective analysis was conducted on the clinical data of 402 patients with sepsis. According to the occurrence of acute liver injury during ICU stay， the patients were divided into a sepsis with liver injury group and a sepsis without liver injury group. Univariate analysis was used to screen clinical indicators potentially associated with liver injury， and a multivariate Logistic regression model was then established to identify the independent risk factors for acute liver injury in sepsis patients. ResultsA total of 229 sepsis patients who met the inclusion criteria were enrolled， among whom 110 cases （48.03%） had liver injury， and 52 patients （47.27%） in the liver injury group died. There were statistically significant differences between the two groups in APACHE Ⅱ score， SOFA score， platelet count， lactate level， fibrinogen content， diabetes mellitus， abdominal infection， vasoactive drug therapy， continuous renal replacement therapy， and mechanical ventilation therapy （P<0.05）. Multivariate Logistic regression analysis showed that SOFA score （OR=1.19， 95%CI： 1.06 - 1.33）， diabetes mellitus （OR=3.27， 95%CI： 1.65 - 6.48）， abdominal infection （OR=2.74， 95%CI： 1.33 - 5.62）， and mechanical ventilation therapy （OR=5.24， 95%CI： 1.58 - 17.41） were independent risk factors. ConclusionDiabetes， mellitus， abdominal infection， SOFA score， and mechanical ventilation therapy are independent risk factors for acute liver injury in sepsis patients.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To investigate the factors influencing the persistence of prostate specific antigen(PSA) following radical prostatectomy, and to develop and validate a predictive model for PSA persistence.Methods:Clinical data from 1 828 patients who underwent radical prostatectomy at Shanghai Changhai Hospital between January 2015 and December 2023 were retrospectively analyzed. Of these, 1 295 patients from January 2015 to April 2021 comprised the modeling group, while 533 patients from May 2021 to December 2023 formed the validation group. Additionally, 109 patients who underwent radical surgery at the Third Affiliated Hospital of Naval Medical University between March and December 2023 were included as an external validation group. Patients with incomplete clinical information, serum PSA levels exceeding 100 ng/ml, or those who received preoperative neoadjuvant therapy were excluded. Ultimately, 1 003, 369, and 86 patients were included in the modeling, validation, and external validation groups, respectively. The modeling group had serum PSA of 19.29 (8.43, 23.73) ng/ml; the clinical stages were distributed as T 1, T 2, T 3, and T 4 in 191, 673, 123, and 16 patients, respectively; the primary Gleason scores of biopsy were 3, 4, and 5 in 460, 466, and 77 patients, respectively; and the secondary Gleason scores were 3, 4, and 5 in 363, 486, and 154 patients, respectively. The validation group had serum PSA of 12.80 (6.82, 14.40) ng/ml; the clinical stages were distributed as T 1, T 2, T 3, and T 4 in 40, 289, 37, and 3 patients, respectively; the primary Gleason scores of biopsy were 3, 4, and 5 in 218, 145, and 6 patients, respectively; and the secondary Gleason scores were 3, 4, and 5 in 140, 184, and 45 patients, respectively. The external validation group had serum PSA of 12.84 (7.11, 12.97) ng/ml; the clinical stages were distributed as T 1, T 2 and T 3 in 9, 68, and 9 patients, respectively; the primary Gleason scores of biopsy were 3, 4, and 5 in 58, 27, and 1 patient, respectively; and the secondary Gleason scores were 3, 4, and 5 in 28, 50, and 8 patients, respectively. Logistic regression analysis was used to identify independent risk factors for PSA persistence after radical prostatectomy in the modeling group and a prediction model was constructed. The predictive performance of the model was analyzed using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve, the calibration curve, and the clinical decision curve. The predictive performance of the model was verified by the ROC curve in the validation group and the external validation group. Results:The incidence of persistent PSA after surgery in the modeling group, validation group, and external validation group was 8.97% (90/1 003), 7.32% (27/369), and 17.4% (15/86), respectively. In the modeling group, univariate and multivariate logistic regression analysis revealed that serum PSA, percentage of positive needle cores, primary Gleason score on biopsy, and secondary Gleason score on biopsy were independent risk factors for PSA persistence ( P<0.05), and a prediction model was constructed based on these factors. The AUC value of this model was 0.790 (95% CI 0.745-0.835). Calibration curve and clinical decision curve analyses showed that the model's predicted probabilities aligned well with actual risks within the 0-40% prediction interval, providing clinical benefit. The AUC values of the ROC curves in the validation group and external validation group were 0.808 (95% CI 0.719-0.897) and 0.822 (95% CI 0.714-0.929), respectively, indicating that the model had good predictive performance. Conclusions:The predictive model for PSA persistence, constructed based on serum PSA, percentage of positive needle cores, primary and secondary Gleason score on biopsy, demonstrated good clinical predictive performance, exhibiting high accuracy in both internal and cross-center validation.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

AIM To investigate the effects of Liangxue Heying Formula-medicated serum(LXHY-MS)on human umbilical vein endothelial cells(HUVECs)induced by lipopolysaccharide(LPS).METHODS CCK-8,DCFH-DA fluorescence probe and Western blot method were used to screen the LPS concentration in modeling and the serum LXHY concentration for treatment.The HUVECs divided into the normal group,the model group and the LXHY-MS group had their SOD activity detected by automatic biochemical analyzer;their MDA level detected by colorimetry;their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 detected by Western blot;and their mROS expression and recruitment effect on THP-1 photographed with high connotation.With the use of JAK2/STAT3 pathway inhibitor(AG490),the HUVECs divided into the normal group,the AG490 group,the LPS group,the LPS+AG490 group,the LPS+LXHY-MS group,and LPS+LXHY-MS+AG490 group were subjected to the corresponding treatment,followed by the detection of their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 by Western blot.RESULTS Compared with the normal group,the model group displayed decreased SOD activity(P＜0.01),increased MDA level(P＜0.05),increased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),and increased mROS expression and THP-1 cells recruitment.Compared with the model group,the LXHY-MS group shared increased SOD activity(P＜0.05),decreased MDA level(P＜0.01),decreased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),reduced mROS expression and THP-1 cells recruitment.Given the use of AG490,the model group displayed increased protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 in contrast to the normal group(P＜0.05,P＜0.01);each intervened group showed decreased expressions of related proteins in contrast to the model group(P＜0.05,P＜0.01).CONCLUSION LXHY-MS may protect the injury due to the activation of HUVECs by inhibiting the JAK2/STAT3 signaling pathway.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.