Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.

OBJECTIVE: To compare the effectiveness and shoulder function of reverse total shoulder arthroplasty (RTSA) and open reduction and internal fixation (ORIF) in the treatment of Neer three/four-part proximal humeral fractures in the elderly. METHODS: Randomized controlled analysis was conducted on 68 patients over 70 years old with Neer three/four-part proximal humeral fractures treated with RTSA or ORIF between January 2020 and June 2022. The patients were randomly divided into RTSA group ( n=32) and ORIF group ( n=36). There was no significant difference ( P>0.05) in the baseline data such as age, gender, body mass index, injured side, Neer classification, and preoperative Charlson comorbidity index, visual analogue scale (VAS) score, Constant shoulder score, Oxford shoulder score (OSS), and hemoglobin (Hb). The operation time, intraoperative blood loss, reduction of Hb on the 3rd day after operation, hospital stay, total cost of hospitalization, complication incidence, range of motion of shoulder joint at 2 years after operation, VAS score before operation and at 5 days and 1 month after operation, Constant shoulder score and OSS score before operation and at 2 years after operation, and imaging results during follow-up were recorded and compared between the two groups. RESULTS: Compared with the ORIF group, the RTSA group had longer operation time, less intraoperative blood loss, and higher total cost of hospitalization ( P<0.05). There was no significant difference in Hb reduction on the 3rd day after operation between the two groups ( P>0.05). The VAS scores significantly improved in both groups at 5 days and 1 month after operation ( P<0.05), but there was no significant difference between the two groups ( P>0.05). All patients were followed up 26-35 months, with an average of 31.2 months. In the RTSA group, there were 2 cases of poor healing of superficial incision and 1 case of transient nerve injury. There was no complication such as bone resorption around the prosthesis, lucent band, prosthesis loosening, or periprosthetic fracture in all patients. In the ORIF group, there was 1 case of poor healing of superficial incision, 3 cases of nonunion of fracture, 1 case of arthritis secondary to humeral head necrosis, and 1 case of bone absorption of large tuberosity, and no displacement or fracture failure of internal fixation was found in all patients. There was no significant difference in the incidence of complications [9.4% (3/32) vs 16.7% (6/36)] between the two groups [ OR (95% CI): 0.828 (0.171, 4.014), P=0.814]. In the RTSA group, 28 cases were graded 0 and 4 cases were graded 1 at 2 years after operation. Constant and OSS scores of RTSA group were significantly better than those of ORIF group ( P<0.05). The Constant score was significantly better than ORIF group in activity and strength, range of motion, lifting, abduction, and external rotation ( P<0.05), and there was no significant difference in pain, daily function, and internal rotation between the two groups ( P>0.05). The RTSA group had a significantly greater range of motion in lifting, abduction, and external rotation than ORIF group ( P<0.05), but there was no significant difference in internal rotation between the two groups ( P>0.05). CONCLUSION Application of RTSA as the initial treatment of Neer three/four-part proximal humeral fractures in the elderly can achieve better rehabilitation of joint activity and lower risk of early reoperation, and improve the quality of life of elderly fracture patients. However, the difficulty of revision and the high cost of treatment require the surgeon to pay full attention and strictly grasp the indications.
Humans ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Shoulder Fractures/surgery* ; Arthroplasty, Replacement, Shoulder/methods* ; Aged ; Bone Plates ; Open Fracture Reduction/methods* ; Range of Motion, Articular ; Treatment Outcome ; Shoulder Joint/physiopathology* ; Aged, 80 and over ; Operative Time ; Postoperative Complications/epidemiology* ; Length of Stay

Objective To investigate the role and mechanism of the zinc finger protein Kruppel-like transcription factor 9 (KLF9) in the stimulation of type I interferon expression induced by herpes simplex virus type 1 (HSV-1) in macrophages. Methods Agarose Gel electrophoresis, quantitative real-time PCR (qRT-PCR) and western blot analyses were employed to detect the KLF9 relative expression in bone marrow-derived macrophages (BMDMs) from Klf9^-/- (gKO) mice and wild-type (WT) mice. RNA-seq analysis was utilized to identify the potential targeted genes upon HSV-1 stimulation in BMDMs. ELISA was used to measure the potent of IFN-β in the supernatant of BMDMs derived from gKO and WT mice after HSV-1 stimulation. qRT-PCR analysis was employed to further confirm the changes of Ifnb1 and interferon-stimulated gene (ISG) such as interferon-induced protein with tetratricopeptide repeats 1 (Ifit1), interferon-stimulated exonuclease gene 20 (Isg20), cholesterol 25-hydroxylase (Ch25h) and 2'-5' oligoadenylate synthetase-like 1 (Oasl1). Western blot was used to detect the expression of phosphorylated interferon regulatory factor-3 (p-IRF3), IRF3, phosphorylated interferon regulatory factor-7 (p-IRF7), IRF7, phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) and NF-κB p65. CUT-Tag and ChIP-qPCR assay were utilized to confirm the binding region of KLF9 in Ifnb1. Results The KLF9 expression was significantly decreased in BMDMs from gKO mice compared with that from WT mice. The RNA-seq analysis showed that Klf9 deletion in BMDMs resulted in an impaired type I interferon signaling pathway. The qRT-PCR analysis revealed that Klf9 deletion in BMDMs led to a significant decrease of Ifnb1 and ISG such as Ifit1, Ch25h and Oasl1 except Isg20. Moreover, ELISA revealed that Klf9 knockout in BMDMs resulted in a significant decrease of IFN-β secreted from BMDMs. Mechanistically, KLF9 directly binds to the promoter of Ifnb1. Conclusion KLF9 is essential for macrophages to resist HSV-1 infection.
Animals ; Kruppel-Like Transcription Factors/physiology* ; Interferon-beta/metabolism* ; Macrophages/virology* ; Mice ; Herpesvirus 1, Human/physiology* ; Mice, Knockout ; Signal Transduction ; Mice, Inbred C57BL ; Interferon Regulatory Factor-3/genetics* ; Interferon Regulatory Factor-7/genetics* ; Gene Expression Regulation

OBJECTIVE: To design a series of geometric indexes, which can improve the correlation between geometric parameters and dosimetric parameters. METHODS: 48 cases of upper abdomen were selected. Manual and automatic segmentation were performed for two organs at risk, which were stomach and duodenum. Three overlapping structures, which were the overlaps with target expanded by 5 mm, 10 mm and 20 mm, were generated for each organ at risk. The geometric parameters of overlapping structures were calculated. The relationship between these geometric parameters and the dosimetric parameters of organs was investigated. RESULTS: When the geometric parameters of overlapping structures related to the target expand 5 mm, 10 mm and 20 mm were larger than 0.4, 0.6 and 0.8 respectively, the maximum dose differences of manual and automatic segmentation were less than 3 Gy. For the case with no overlaps between the organs and the target expansions, the overlap structure corresponding to target expanding 20 mm were recommended for safety considerations. CONCLUSIONS For organs at risk in the upper abdomen, the overlapping geometric parameters were closely related to the maximum dose of organs. Overlapping geometric parameters could predict whether the difference of maximum dose caused by automaticsegmentation was clinically acceptable or not.
Organs at Risk ; Radiometry ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated

Objective:To evaluate the effect of implementation of prevention from mother-to-child transmission of syphilis in Minhang district of Shanghai from 2013 to 2019.Methods:The data of 284 pregnant women with syphilis infection diagnosed by 6 midwifery medical institutions in Minhang District from January 2013 to December 2019, were collected from the database of national management information system for prevention of mother to child transmission of AIDS, syphilis and hepatitis B. Among them there were 1 case of spontaneous abortion, 4 cases of ectopic pregnancy, 42 cases of lost follow-up; the remaining 237 parturients were included in this study. The Implementation Program of prevention of mother-to-child transmission of AIDS, syphilis and hepatitis B (2015 edition) has been implemented since 2015 in Minhang district. The maternal and neonatal outcomes between the period of 2013-2015 (before program implemented, 123 cases) and the period of 2016-2019 (after program implemented, 114 cases) were compared. Results:Between 2013 and 2019, the syphilis detection rate of pregnant women remained 100.00% (100 761/100 761). The detection rates during pregnancy before and after program implementation were 95.92% (51 855/54 288) and 98.87% (45 949/46 473); the prevalence rate of syphilis was 2.93‰ (159/54 288) and 2.69‰ (125/46 473), respectively. The rate of anti-syphilis treatment was 62.60% (77/123) and 85.96% (98/114), the standard treatment rate was 20.33% (25/123) and 49.12% (56/114), the neonatal preventive treatment proportion/rate was 1/12 and 94.74% (72/76). The detection rate during pregnancy, anti-syphilis treatment rate, standardized treatment rate and neonatal preventive treatment rate after program implementation were significantly higher than those of before implementation (χ 2=988.88, 16.72, 21.81, 54.72, all P<0.01). The rate of non- Treponema pallidum antigen titer ≥ 1∶8 was 36.89% (38/103) and 17.48% (18/103), respectively in two periods; the incidence of neonatal adverse health problems was 21.49% (26/121) and 6.03% (7/116); congenital syphilis report incidence rate was 152.12/100 000 live births (83/54 562) and 23.46/100 000 live births (11/46 890), respectively. All these indicators showed a significant reduction (χ 2=9.81, 11.80, 45.10, all P<0.01). The treatment rate of pregnant women with previously diagnosed syphilis infection was 63.27% (62/98), which was lower than that of those with initially diagnosed (81.29%, 113/139) ( cOR=2.52, 95 %CI: 1.40-4.56, χ 2=9.672, P<0.01). Among whose with lost follow-up, the floating pregnant women accounted for 92.86% (39/42), 57.14% (24/42) of whom were unable to contact and 30.95% (13/42) refused to be followed up. Conclusions:After the implementation of prevention program, the rates of detection and diagnosis, standardized treatment, neonatal preventive treatment, as well as the maternal and neonatal outcomes of pregnant women with syphilis infection have been significantly improved in Minhang district of Shanghai.

BACKGROUND:Current research on mesenchymal stem cels (MSCs) is mostly focused on its immune regulatory function, while little is reported on the antioxidant capacity of the cels and culture supernatant.OBJECTIVE: To investigate the anti-oxidative capacity of the supernatant harvested from human fetal placenta MSCs (fPMSCs) under a condition of serum free culture. METHODS:fPMSCs were cultured with serum free media, and the supernatants of cels at passages 2-6 were colected at 48 hours after culture. Vitamin C was added into the culture medium, as a positive control, and its concentration was 100 μmol/L. The total antioxidant capacity, scavenging capacity of free radicals and antioxidant enzymatic activities of supernatants were measured. RESULTS AND CONCLUSION: By comparing anti-oxidative activities of vitamin C and na?ve culture medium, supernatants colected from fPMSCs cultures exhibited obvious antioxidant capacities at different extents between passages of cel cultures. The total antioxidant capacity of the culture supernatant was comparable to 40-80 μmol/L vitamin C. In addition, al supernatants derived from cels with different passages displayed capacities to scavenge free radicals, including 2,2-diphenyl-1-picrylhydrazyl radical (DPPH?), hydroxyl radical (?OH), superoxide anion radical (O2-). Even more, activities of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, were also detected in supernatants colected from different passages of fPMSCs. Under the serum-free condition, the culture supernatants of fPMSCs have antioxidant capacities at certain extent. However, the antioxidant components and underlying mechanisms need to be further studied.

Amyloidosis ; Cardiomyopathy, Hypertrophic ; Humans

Objective To explore the abnormal karyotype characteristics of myelodysplastic syndrome (MDS)patients and their correlation with clinical prognosis.Methods Analyzed the karyotypes of 281 MDS patients by use of G-banding tech-nique.Results Through analysis of the karyotypes of 281 MDS patients,found that the percentage of abnormal karyotypes was 48.75% (137/281),among 137 patients with abnormal karyotypes,43.07% (59 cases)presented with numerical aber-ration,31.39% (43 cases)with structural aberration,and 25.54% (35 cases)with both numerical and structural abnormali-ties.As for MDS subtypes,the occurrence rate of abnormal karyotype was 63.41% (26/41)in RAEB-2,58.73% (37/63)in RAEB-1,39.2% (49/125)in RCMD,15.38% (2/13)in RAS and 22.58% (7/31)in RA.The rates of abnormal karyotype in RAEB-1 and RAEB-2 were significantly higher than that in RA and RAS(P<0.01),and in RCMD (P <0.05).The fre-quent abnormal karyotypes were as follows:+8,-7/7q-,-20/20q-,complex karyotypes chromosomal translocation,i(17),-Y and +21.The follow-up study of 159 MDS patients indicated that the median survival time was 39 months for 68 patients with normal karyotypes and 21 months for 91 patients with abnormal karyotypes,the former was significantly prolonged than the latter (P < 0.05).As far as the leukemia transition rate was concerned,the patients with aberrant karyotypes (35.5%)were significantly higher than that with normal karyotypes (10.3%)(P < 0.01),among them,the cases with complex karyotypes and-7/7q-more easily transit into leukemia.Conclusion MDS was one kind of clonal hematological ma-lignancy with high heterogeneity.Chromosomal karyotype test plays an important role in the correct diagnosis,typing and prognosis evaluation of MDS.

Objective The purpose of this paper is to understand the advantages and disadvantages of the bone marrow smears and bone marrow biopsy in multiple myeloma diagnosis and efficacy judgment,explicit the value of bone marrow smears and bone marrow biopsy synchronous check in the diagnosis and treatment observation of multiple myeloma.Methods With two step-suction two biopsy specimens assay,obtained specimens of bone marrow smears and bone marrow biopsy,retrospective-ly analysed results of 283 multiple myeloma patients bone marrow smear and biopsy,and made a comparative study on the degree of bone marrow hyperplasia,myeloma cell morphology,the degree of tumor cell infiltration,proliferation pattern,bone marrow stromal pathological changes,and fibrosis cases.Results The degree of proliferation of bone marrow biopsy sections and infiltration of plasma cells was significantly higher than that of bone marrow smears,statistically there was a significant difference (P <0.01).Multiple myeloma diagnostic sensitivity by bone marrow biopsy sections was significantly higher than by the bone marrow smears,the difference was statistically significant (P < 0.05).Plasma cells in bone marrow biopsy tumor proliferation modes:clusterpiece nodular type 33 cases (11.66%),interstitial-type 86 cases (30.39%),among nodular interstitial type 112 cases (39.58%),diffuse cypriot real 52 cases (18.37%).Plasma cells in bone marrow smears tumor morphology:small mature plasma cell type 77 cases (27.21%),immature plasma cell type 148 cases (52.30%),protoplas-mic cell type 36 cases (12.72%),reticular plasma cell type 22 cases (7.77%).Conclusion Marrow biopsy can accurately reflect the degree of bone marrow hyperplasia,plasma cell tumor proliferation mode and infiltration degree,myelofibrosis sit-uation;bone marrow smears Wright-Giemsa staining,plasma cell tumor morphology was clear,typicalfeatured,and easily i-dentifiable.Bone marrow smear and biopsy synchronous check can improve the sensitivity and accuracy for multiple myeloma diagnosis,which has very important significance for multiple myeloma diagnosis and treatment observation.