Factors associated with early failure of the femoral neck system (FNS) in patients with femoral neck fractures.

BACKGROUND: Femoral neck system (FNS) is a new type of internal fixation system which has been widely used for treating femoral neck fractures (FNFs).Compared with other internal fixation methods, FNS is minimally invasive and stable, and often achieves satisfactory short-term efficacy.Early failure of FNS (EFFNS) is not uncommon, however, there are few literatures and reports on factors associated with EFFNS.This study aimed to survey the prevalence and risk factors of EFFNS. METHODS: We retrospectively analysed 62 patients with FNFs and underwent FNS fixation between 2019 and 2021. Demographic data, clinical characteristics, radiographic features and treatment process were described. Multifactor logistic regression analysis was used to analyse the different influencing factors. RESULTS: Out of the 62 FNFs patients, 10 patients (16.1%) developed EFFNS, including 6 cases of severe femoral neck shortening, 2 cases of screw-out, 1 case of avascular necrosis of the femoral head and 1 case of nonunion. In the failure group, all patients were younger than 65 years old, which was significantly higher than 59.6% in the healing group (P = 0.012). There were no significant differences in sex(P = 0.490), BMI (P = 0.709), injured side (P = 0.312), injury mechanism (P = 0.617), reduction method(P = 0.570),femoral neck-shaft angle(P = 0.545), Pauwels classification (P = 0.564) and Garden classification (P = 0.195). Moreover, we not found that Garden classification (P = 0.464) and age (P = 0.128) were statistically significant risk factors for EFFNS at multivariate analysis. CONCLUSION: In this study, sex, BMI, injury side, injury mechanism, reduction method, Pauwels angle, femoral neck-shift angle, Pauwels classification and Garden classification were excluded as EFFNS risk factors. Moreover, our study demonstrated that age and Garden classification were not significant risk factors at multivariate analysis. TRIAL REGISTRATION: ChiCTR, ChiCTR2100051360. Registered on 21 September, 2021. https://www.chictr.org.cn/index.aspx .

[Study of R2* value to evaluate regulation of liver regeneration by hepatic warm ischemia-reperfusion injury after partial hepatectomy in rabbits].

Objective: To investigate the effect of R2* value on the evaluation of different degrees of hepatic warm ischemia-reperfusion injury (WIRI) and liver regeneration after partial hepatectomy in rabbits. Methods: Thirty healthy adult male New Zealand White rabbits were randomly divided into five groups. Hepatic caudal lobectomy was performed in both the control and the warm ischemia time-dependent variation group. After reperfusion, routine MRI and BOLD MRI scans were performed for each group at 6 h, 3 d, 7 d, 14 d and 30 d, respectively, and then R2* value and liver regeneration rate (LRR) were measured and calculated. After 30 days of scanning, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) were detected in frozen rabbit liver tissues, and the pathological sections were collected. Repeated measures analysis of variance was used to evaluate the changes of R2* value, LRR and its influencing factors at different follow-up time and warm ischemia time in each group. Pearson's or Spearman's correlation analysis was used to evaluate the correlation of R2* value with LRR and various biochemical indexes. Results: The interaction between different follow-up time and warm ischemia time (F = 24.600, P < 0.001) and the single effect of the both on the R2* value had statistically significant difference (P < 0.05). The interaction of different follow-up time and different warm ischemia time had no effect on LRR, and the difference was not statistically significant (F = 0.925, P = 0.528), but the difference in the main effect of the both on LRR was statistically significant (P < 0.05). At the same follow-up time, except for the 40-min ischemia group, the R2* values ​​were significantly positively correlated with LRR (3, 7, 14, 30 days after operation, r = 0.510, 0.681, 0.612, 0.541 respectively, P < 0.05). At the same warm ischemia time, the R2* value were significantly negatively correlated with LRR (3, 7, 14, 30 and 40 days after operation, r = - 0.800, -0.852, -0.893, -0.648, -0.853, respectively, P < 0.05). There was no correlation between R2 * value and biochemical indexes at 30 days after operation (P > 0.05). Conclusion: The R2* value may be used for noninvasive and quantitative evaluation of microstructural changes of WIRI and affect liver regeneration after partial hepatectomy in rabbits. A certain degree of WIRI (≤30 min) after partial hepatectomy can promote liver regeneration in rabbits. Furthermore, as the warm ischemia time prolongs, the promoting effect becomes more pronounced, and if the warm ischemic time exceeds 30 minutes, the promoting effect is significantly reduced.

[Alveolar capillary dysplasia with misalignment of the pulmonary veins: a case report and literature review].

Objective: To investigate the clinical, pathological and genetic characteristics of neonatal alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV). Methods: The clinical manifestations, radiographic examinations, pathology and parental genetic analysis of a newborn with FOXF1 variation induced ACDMPV, who was hospitalized in the Department of Neonatology of Shenzhen Children's Hospital in January 2020, were extracted and analyzed. Related literature up to March 2020 with the key words of "Alveolar capillaries dysplasia" "Alveolar capillary dysplasia with misalignment of the pulmonary veins" "FOXF1" in PubMed, CNKI, Wanfang, CQVIP database and Leiden Open Variation database (LOVD) were searched. Results: A full-term male newborn （1 hour of age） was admitted due to anal atresia. Surgical repair of anal atresia and omphalocele was performed on the first day of life, and gallbladder absence and Meckel's diverticulum were identified during the operation. Respiratory distress with hypoxemia developed at about 6 hours of life, and persistent pulmonary hypertension developed and progressed after surgery, with poor response to mechanical ventilation and pulmonary vasodilators. This infant passed away at 26 days of life. Lung biopsy showed decreased alveolar units and thickened interalveolar septa, reduced alveolar capillary density and thickened walls of peripheral pulmonary arteries, and misaligned pulmonary veins adjacent to the pulmonary arterioles, which were consistent with ACDMPV. The whole exome sequencing revealed a heterozygous novel frameshift of FOXF1 gene located in chromosome 16q24.1 c376_377insT; p.(Pro126fs). According to the bioinformatics analysis, this variation was likely to be pathogenic as it was associated with coding disorder of FOXF1 Pro126, resulting in truncation of the encoded protein. This novel variation had not been reported in the human gene mutation database (HGMD), ESP6500siv2_ALL, 1000g2015aug_ALL or dbSNP147 database. Previous 6 literatures reported 54 variants, including 28 missense, 10 nonsense, 11 frameshift, 2 deletion, 1 synonymous, and 2 extensions. Only three of the reported 45 cases （24 males, 21 females） were still alive as of the time of this study. Conclusions: Typically, ACDMPV is a catastrophic disease in neonatal period with high mortality. Lung biopsy and genetic testing should be considered in infants who present with persistent pulmonary hypertension and refractory hypoxemia, especially when combined with extrapulmonary abnormalities.

Effect of PMPA and PMEA on the kinetics of viral load in simian immunodeficiency virus-infected macaques.

In this study we compared the effect of postexposure treatment of the acyclic nucleoside analogs 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) and 9-(2-phosphonylmethoxypropyl)-adenine (PMPA) on the kinetics of viral load in the blood and lymph nodes of rhesus macaques chronically infected with SIVmac251 for 18 weeks. Two of the four macaques treated with PMPA (20 mg/kg per day) for 28 consecutive days had demonstrable reductions in viral loads of 1.5 and 3 logs. Three of four macaques given the same dosing regimen of PMEA had viral load reductions ranging from 1.25 to 2.8 logs. Furthermore, treatment with either drug caused a reduction in virus burden in the lymph nodes by 2 weeks posttreatment. However, in both PMEA- and PMPA-treated animals, viral loads rebounded to day of treatment levels by 2 weeks after termination of treatment. The extent to which viral load was suppressed was similar for both drugs. In contrast, viral loads in three of four mock-treated animals remained persistently high throughout the study. This study has demonstrated that postexposure treatment with these acyclic nucleoside analogs could modulate the kinetics of viral load reduction in some animals.

Limited protection from a pathogenic chimeric simian-human immunodeficiency virus challenge following immunization with attenuated simian immunodeficiency virus.

Two live attenuated single-deletion mutant simian immunodeficiency virus (SIV) constructs, SIV239Deltanef and SIVPBj6.6Deltanef, were tested for their abilities to stimulate protective immunity in macaques. During the immunization period the animals were examined for specific immune responses and virus growth. Each construct generated high levels of specific immunity in all of the immunized animals. The SIV239Deltanef construct was found to grow to high levels in all immunized animals, with some animals remaining positive for virus isolation and plasma RNA throughout the immunization period. The SIVPBj6.6Deltanef was effectively controlled by all of the immunized animals, with virus mostly isolated only during the first few months following immunization and plasma RNA never detected. Following an extended period of immunization of over 80 weeks, the animals were challenged with a pathogenic simian-human immunodeficiency virus (SHIV) isolate, SIV89. 6PD, by intravenous injection. All of the SIV239Deltanef-immunized animals became infected with the SHIV isolate; two of five animals eventually controlled the challenge and three of five animals, which failed to check the immunizing virus, progressed to disease state before the unvaccinated controls. One of five animals immunized with SIVPBj6.6Deltanef totally resisted infection by the challenge virus, while three others limited its growth and the remaining animal became persistently infected and eventually died of a pulmonary thrombus. These data indicate that vaccination with attenuated SIV can protect macaques from disease and in some cases from infection by a divergent SHIV. However, if animals are unable to control the immunizing virus, potential damage that can accelerate the disease course of a pathogenic challenge virus may occur.

Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety.

Balanol is a potent protein kinase C (PKC) inhibitor that is structurally composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine ring. A number of balanol analogs in which the perhydroazepine moiety is replaced have been synthesized and their biological activities evaluated against both PKC and cAMP-dependent kinase (PKA). The results suggested that the activity and the isozyme/kinase selectivity of these compounds are largely related to the conformation about this nonaromatic structural element of the molecules.

Naturally occurring protein kinase C inhibitors; II. Isolation of oligomeric stilbenes from Caragana sinica.

The oligomeric stilbenes (+)-alpha-viniferin (1), miyabenol C (2), and kobophenol A (3) have been isolated from Caragana sinica (Buchoz) Rehd (Leguminosae). (+)-alpha-Viniferin (1) and miyabenol C (2) exhibited protein kinase C inhibitory activity at low micromolar concentrations. (+)-alpha-Viniferin inhibited keratinocyte proliferation (0.4 microM) and free radical release in whole blood (47 microM), in vitro, and may be useful in treating hyperproliferative or inflammatory skin diseases.

A diaminoantraquinone inhibitor of angiogenesis.

Tumor growth is dependent upon angiogenesis. There is an intense search for pharmacological inhibitors of angiogenesis as a novel approach to treat angiogenic diseases, e.g., arthritis, diabetic retinopathy or cancer. A series of compounds, originally studied as potential protein kinase C inhibitors, included the diaminoanthraquinone NSC 639366 (1-[[3-(diethylamino)-2-hydroxypropyl]amino]-4-[(2,3- epoxypropyl)amino]-9,10-anthracenedione fumaric acid salt) (SPC-100097), was found to reversibly inhibit bovine endothelial cell growth with an IC50 that ranged between 1 and 4 nM. NSC 639366 reversibly inhibited endothelial cell migration, particularly endothelial cells stimulated by the potent angiogenic molecule, basic fibroblast growth factor. The activity of secreted urokinase-type plasminogen activator and active interstitial collagenase, but not gelatinase, was inhibited by NSC 639366. In vivo, angiogenesis was significantly inhibited by NSC 639366 by using the chick chorioallantoic membrane or the rat corneal bioassay. Two analogs of NSC 639366 did not inhibit endothelial cell growth. These experiments introduce a novel compound that could be clinically useful against angiogenic diseases and encourage further development of compounds that inhibit the plasminogen-plasmin system known to be a key regulator of angiogenesis.

Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids.

Betulinic acid [1] and platanic acid [2], isolated from the leaves of Syzigium claviforum, were found to be inhibitors of HIV replication in H9 lymphocyte cells. Evaluation of anti-HIV activity with eight derivatives of 1 revealed that dihydrobetulinic acid [3] was also a potent inhibitor of HIV replication. The C-3 hydroxy group and C-17 carboxylic acid group, as well as the C-19 substituents, contribute to enhanced anti-HIV activity. The inhibitory activity of these compounds against protein kinase C (PKC) was also examined, since a correlation between anti-HIV and anti-PKC activities has been suggested. However, there was no apparent correlation between anti-HIV activity and the inhibition of PKC among these compounds.

New hexahydroxybiphenyl derivatives as inhibitors of protein kinase C.

We have previously shown that some ellagitannins are potent inhibitors of protein kinase C (PKC). On the basis of this finding, several series of hexahydroxybiphenyl derivatives of ellagic acid were synthesized as simple analogs of these ellagitannins and were evaluated for their inhibitory effect against PKC. Compounds 23 and 26 were found to be potent inhibitors of PKC, while hexakis-(benzyloxy)biphenyl derivatives exhibited weak anti-PKC activity.

XB596, a promising bis-naphthalimide anti-cancer agent.

We have synthesized a promising class of bis-naphthalimide anti-tumor agents. A representative compound in this series, XB596, exhibits potent in vitro growth inhibitory activity against several human and murine leukemic and solid tumor lines in culture, with IC50 values ranging from 7.2 to 147.5 nM. XB596 was almost as equally growth inhibitory against three doxorubicin-resistant cell lines compared with their parental lines. Using a human tumor colony-forming assay, XB596 demonstrated cytocidal activity against fresh human tumors taken directly from patients, with 23 of 25 evaluable tumors responding to a continuous exposure of 1 microgram/ml of XB596. When L1210 cells were incubated with XB596 for 1 h, the incorporation of uridine and thymidine into RNA and DNA, respectively, was inhibited with IC50 values of 0.14 microM. DNA single-strand breaks, but not double-strand breaks, were detected in XB596-treated L1210 cells. XB596 bound to DNA with guanine-cytosine sequence selectivity as shown by an indirect ethidium bromide displacement assay. XB596 was shown to interact with DNA by a spectrophotometric titration assay, with an estimated binding constant of 4.7 +/- 2.2 +/- 10(6) M-1. XB596 unwound supercoiled DNA as measured by agarose gel electrophoresis. These data are consistent with XB596 being a DNA intercalator. In vivo, XB596 demonstrated good anti-tumor activity against two human solid tumors (DLD-2 colon adenocarcinoma and MX-1 mammary carcinoma) xenografted in nude mice, but has not demonstrated anti-leukemic activity. In summary, XB596 is a pre-clinical anti-cancer agent which interacts with DNA and demonstrates good in vivo anti-tumor activity against human solid tumor xenografts.

Novel non-cross resistant diaminoanthraquinones as potential chemotherapeutic agents.

A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and NSC 639366 (4) in human tumor cloning assay showed potent cytocidal activity. The results suggest therapeutical potentials against human tumors.

Antitumor agents. 134. New shiraiachrome-A- and calphostin-C-related perylene derivatives as cytotoxic and antiviral agents and inhibitors of protein kinase C.

Shiraiachrome-A and -B have been isolated from the mycelium of the Chinese bamboo fungus Shiraia bambusicola as the cytotoxic principles. A series of new perylene derivatives (7-27) related to Shiraiachrome-A and -B as well as Calphostin-C have been synthesized and evaluated for their cytotoxicity, antiviral activity, and inhibitory activity against protein kinase C. The results indicated that 11 and 12 are potent cytotoxic agents against HCT-8, RPMI-7951, and TE-671 solid tumor cells, whereas 24 and 26 demonstrated strong antiviral activity against HSV-1 and HSV-2. Compound 10 is an inhibitor of protein kinase C.

Investigation of the mechanism of the interaction of tubulin with derivatives of 2-styrylquinazolin-4(3H)-one.

A new class of antimitotic agents, derivatives of 2-styrylquinazolin-4(3H)-one (SQZ), was recently described [J. Med. Chem. 33:1721-1728 (1990)]. Because they appeared to interact at a new ligand binding site on tubulin, we attempted to determine their mechanism of action as inhibitors of tubulin polymerization. Although in initial studies inhibition of colchicine binding was negligible, substantial and competitive inhibition of this reaction could be demonstrated with very short incubation times (less than 5 min), provided that a relatively low colchicine to tubulin ratio was used. The initial apparent failure to inhibit colchicine binding resulted from extremely rapid binding to tubulin and dissociation from tubulin by the SQZ derivatives, in comparison with the slow, temperature-dependent, poorly reversible binding of colchicine. The most inhibitory of the SQZ derivatives in the colchicine binding assay was 6-methyl-2-styrylquinazolin-4(3H)-one (NSC 379310), and its interaction with tubulin, particularly as an inhibitor of colchicine binding, was compared with that of 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone (MTPT), because the binding parameters of MTPT with tubulin have been well described. The data indicate that NSC 379310 binds to tubulin and dissociates from the protein about 3 times as rapidly as MTPT. The other SQZ derivatives with equal or greater potency as inhibitors of tubulin polymerization but apparently less potency as inhibitors of colchicine binding presumably bind to and/or dissociate from tubulin even more rapidly than does NSC 379310.

Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization.

A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.

[Induction of retarded exoerythrocytic schizonts by chloroguanide resulting in delayed parasitaemia of Plasmodium inui in Macaca mulatta].

Three Rhesus monkeys inoculated with a large number of sporozoites of Plasmodium inui dissected from the salivary glands of infected mosquitoes, Anopheles dirus. Two of the monkeys (inoculated with 8.06 x 10(5) and 1.3 x 10(7) sporozoites, respectively) were treated with chloroguanide base 6 mg/(kg.d) x 4 d starting from 24 h after the inoculations and the other one (inoculated with 5.93 x 10(6) sporozoites) was not treated with chloroguanide as control. The primary parasitaemia attacks occurred in the former 2 monkeys were 31 and 25 d respectively after inoculation, while in the control was 7.5 d. Liver biopsies were done in all of the 3 monkeys, normal schizonts were seen in the control monkey on d 8 after inoculation, while none were detected in the 2 monkeys treated with chloroguanide. However, the retarded exoerythrocytic schizonts were found by indirect fluorescent antibody test (IFAT) in liver sections of the monkey inoculated with 1.3 x 10(7) sporozoites. Therefore, it is evident that moderate doses of chloroguanide retarded the formation of schizonts and thus delayed the primary parasitaemia.

An ultrastructural study of the exoerythrocytic schizonts of Plasmodium cynomolgi and P. knowlesi in Macaca mulatta.

Exoerythrocytic schizonts of Plasmodium cynomolgi and P. knowlesi were examined by electron microscopy in biopsy samples of primate livers. With maturity the parasitophorous vacuole membrane becomes highly sculptured by the addition of a discontinuous dense thickening, the distribution of which can be a distinguishing character between these two species. The parasitophorous vacuole membrane follows the contours of the parasite faithfully with a minimal surrounding vacuole. The marked destruction of the cytoplasm of the host hepatocyte by most of the parasites studied however gave the distinct, but erroneous, appearance of a large parasitophorous vacuole at the light microscope level. The mature parasite often exhibited a highly invaginated surface contour with the result that the cytoplasm of the host cell and parasite became intimately interdigitated, this interweaving is unlikely to be recognized in light microscopic studies.