Prevalence of mental health symptoms and associated risk factors among healthcare workers in specialized COVID-19 hospitals in Anyang, China: A cross-sectional survey.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic spread worldwide and brought unprecedented challenges to healthcare systems. Healthcare workers experienced tremendous pressure and psychological issues. Methods: A cross-sectional online survey was conducted from January 2022 to April 2022 among healthcare workers in Anyang, Henan Province, China. Insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), and problematic internet use (PIU) were evaluated. Logistic regression analyses were used to explore the factors that were associated with mental health problems. Results: A total of 242 participants (mean [SD] age, 34.7 [6.6] years, 187 female [77.3 %]) were included in the study. The prevalence of symptoms of insomnia, anxiety, depression, PTSD and PIU during the COVID-19 pandemic in China was 53.7 %, 100.0 %, 7.0 %, 20.3 %, and 19.4 %, respectively. Participants who smoked, used sedative-hypnotic drugs and may need psychological assistance were at a higher risk for mental health problems. Respondents who were older than 45 years and were married displayed a lower risk of insomnia and PTSD, respectively. Conclusions: Mental health symptoms are pervasive among healthcare workers in specialized COVID-19 hospitals during the outbreak. Risk factors include smoking, sedative-hypnotic drug use, and the need for psychological assistance, while protective factors include age and marital status. Developing social media platforms and providing psychological assistance may be effective interventions for healthcare workers.

"Multi-in-One" Yolk-Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade Reactions.

Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2O2) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.

AuPt-Loaded Cu-Doped Polydopamine Nanocomposites with Multienzyme-Mimic Activities for Dual-Modal Imaging-Guided and Cuproptosis-Enhanced Photothermal/Nanocatalytic Therapy.

Nanocatalytic therapy (NCT) has made great achievements in tumor treatments due to its remarkable enzyme-like activities and high specificity. Nevertheless, the limited types of nanozymes and undesirable tumor microenvironments (TME) greatly weaken the therapeutic efficiency. Developing a combination therapy integrating NCT and other strategies is of great significance for optimal treatment outcomes. Herein, a AuPt-loaded Cu-doped polydopamine nanocomposite (AuPt@Cu-PDA) with multiple enzyme-like activities was rationally designed, which integrated photothermal therapy (PTT) and NCT. The peroxidase (POD)-like activity of AuPt@Cu-PDA can catalyze hydrogen peroxide (H2O2) into ·OH, and the catalase (CAT)-mimic activity can decompose H2O2 into O2 to alleviate hypoxia of TME, and O2 can be further converted into toxic ·O2- by its oxidase (OXD)-mimic activity. In addition, Cu2+ in AuPt@Cu-PDA can effectively consume GSH overexpressed in tumor cells. The boosting of reactive oxygen species (ROS) and glutathione (GSH) depletion can lead to severe oxidative stress, which can be enhanced by its excellent photothermal performance. Most importantly, the accumulation of Cu2+ can disrupt copper homeostasis, promote the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), disrupt the mitochondrial tricarboxylic acid (TCA) cycle, and finally result in cuproptosis. Collectively, photothermal and photoacoustic imaging (PTI/PAI)-guided cuproptosis-enhanced NCT/PTT can be achieved. This work may expand the application of nanozymes in synergistic therapy and provide new insights into cuproptosis-related therapeutic strategies.

Unified discontinuous Galerkin finite-element framework for transient conjugated radiation-conduction heat transfer.

Research on conjugated radiation-conduction (CRC) heat transfer in participating media is of vital scientific and engineering significance due to its extensive applications. Appropriate and practical numerical methods are essential to forecast the temperature distributions during the CRC heat-transfer processes. Here, we established a unified discontinuous Galerkin finite-element (DGFE) framework for solving transient CRC heat-transfer problems in participating media. To overcome the mismatch between the second-order derivative in the energy balance equation (EBE) and the DGFE solution domain, we rewrite the second-order EBE as two first-order equations and then solve both the radiative transfer equation (RTE) and the EBE in the same solution domain, resulting in the unified framework. Comparisons between the DGFE solutions with published data confirm the accuracy of the present framework for transient CRC heat transfer in one- and two-dimensional media. The proposed framework is further extended to CRC heat transfer in two-dimensional anisotropic scattering media. Results indicate that the present DGFE can precisely capture the temperature distribution at high computational efficiency, paving the way for a benchmark numerical tool for CRC heat-transfer problems.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

Design, synthesis, and anticancer activity of three novel palbociclib derivatives.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

proBDNF/p75NTR promotes rheumatoid arthritis and inflammatory response by activating proinflammatory cytokines.

P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4+ and CD8+ T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA.

Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.

Background: Tumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined. Methods: Public databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro. Results: PLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to "immune response", "cell cycle", "DNA replication", and "mismatch repair" in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma. Conclusions: PLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma.

Nitrogen and sulfur co-doped carbon dots with bright fluorescence for intracellular detection of iron ion and thiol.

Carbon dots (CDs) have been widely used in recent years because of their excellent water solubility and abundant surface functional groups. However, compared with quantum dots or biological probes, the quantum yield of CDs is lower, and the fluorescence mainly concentrated in the blue-green range, which significantly limits the biological applications of CDs. Heteroatoms doping is the most common method to improve the luminescence of CDs. In this work, nitrogen and sulfur co-doped luminescent CDs were successfully synthesized by microwave assisted method using glutathione (GSH) and p-phenylenediamine (PPD) as raw materials. It can emit bright green fluorescence in ethanol solution, and the maximum emission wavelength is 535 nm when excited at 374 nm, and the absolute quantum yield is as high as 63%. Iron ion (Fe3+) can interact with the functional groups on the surface of the CDs to form CDs/Fe3+, which is a non-fluorescence complex, and Fe3+ can be reduced to ferrous ion (Fe2+). In other words, the reaction mechanism of CDs and Fe3+ is a combination of dynamic quenching and static quenching. The fluorescence of CDs quenched by Fe3+ can be restored by thiol, because there is a stronger binding force between sulfhydryl (-SH) on the surface of thiol and Fe3+, which enables CDs to be released. In addition, the CDs has good biocompatibility and stability, indicating that it has excellent potential in bioimaging. This discovery will expand the application of CDs in the fields of biosensing and imaging.

PDK1 Regulates the Maintenance of Cell Body and the Development of Dendrites of Purkinje Cells by pS6 and PKCγ.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a critical role in the development of mammalian brain. Here, we investigated the role of PDK1 in Purkinje cells (PCs) by generating the PDK1-conditional knock-out mice (cKO) through crossing PV-cre or Pcp2-cre mice with Pdk1fl/fl mice. The male mice were used in the behavioral testing, and the other experiments were performed on mice of both sexes. These PDK1-cKO mice displayed decreased cerebellar size and impaired motor balance and coordination. By the electrophysiological recording, we observed the reduced spontaneous firing of PCs from the cerebellar slices of the PDK1-cKO mice. Moreover, the cell body size of PCs in the PDK1-cKO mice was time dependently reduced compared with that in the control mice. And the morphologic complexity of PCs was also decreased after PDK1 deletion. These effects may have contributed to the reduction of the rpS6 (reduced ribosomal protein S6) phosphorylation and the PKCγ expression in PDK1-cKO mice since the upregulation of pS6 by treatment of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-1, the agonist of mTOR1, partly rescued the reduction in the cell body size of the PCs, and the delivery of recombinant adeno-associated virus-PKCγ through cerebellar injection rescued the reduced complexity of the dendritic arbor in PDK1-cKO mice. Together, our data suggest that PDK1, by regulating rpS6 phosphorylation and PKCγ expression, controls the cell body maintenance and the dendritic development in PCs and is critical for cerebellar motor coordination.SIGNIFICANCE STATEMENT Here, we show the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in Purkinje cells (PCs). The ablation of PDK1 in PCs resulted in a reduction of cell body size, and dendritic complexity and abnormal spontaneous firing, which attributes to the motor defects in PDK1-conditional knock-out (cKO) mice. Moreover, the ribosomal protein S6 (rpS6) phosphorylation and the expression of PKCγ are downregulated after the ablation of PDK1. Additionally, upregulation of rpS6 phosphorylation by3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-1 partly rescued the reduction in cell body size of PCs, and the overexpression of PKCγ in PDK1-KO PCs rescued the reduction in the dendritic complexity. These findings indicate that PDK1 contributes to the maintenance of the cell body and the dendritic development of PCs by regulating rpS6 phosphorylation and PKCγ expression.

Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: a benefit of short-chain fatty acids.

BACKGROUND: Western-style diets arouse neuroinflammation and impair emotional and cognitive behavior in humans and animals. Our previous study showed that a high-fructose diet caused the hippocampal neuroinflammatory response and neuronal loss in animals, but the underlying mechanisms remained elusive. Here, alterations in the gut microbiota and intestinal epithelial barrier were investigated as the causes of hippocampal neuroinflammation induced by high-fructose diet. RESULTS: A high-fructose diet caused the hippocampal neuroinflammatory response, reactive gliosis, and neuronal loss in C57BL/6N mice. Depletion of the gut microbiota using broad-spectrum antibiotics suppressed the hippocampal neuroinflammatory response in fructose-fed mice, but these animals still exhibited neuronal loss. Gut microbiota compositional alteration, short-chain fatty acids (SCFAs) reduction, intestinal epithelial barrier impairment, NOD-like receptor family pyrin domain-containing 6 (NLRP6) inflammasome dysfunction, high levels of serum endotoxin, and FITC-dextran were observed in fructose-fed mice. Of note, SCFAs, as well as pioglitazone (a selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist), shaped the gut microbiota and ameliorated intestinal epithelial barrier impairment and NLRP6 inflammasome dysfunction in fructose-fed mice. Moreover, SCFAs-mediated NLRP6 inflammasome activation was inhibited by histamine (a bacterial metabolite) in ex vivo colonic explants and suppressed in murine CT26 colon carcinoma cells transfected with NLRP6 siRNA. However, pioglitazone and GW9662 (a PPAR-γ antagonist) exerted no impact on SCFAs-mediated NLRP6 inflammasome activation in ex vivo colonic explants, suggesting that SCFAs may stimulate NLRP6 inflammasome independently of PPAR-γ activation. SCFAs and pioglitazone prevented fructose-induced hippocampal neuroinflammatory response and neuronal loss in mice. Additionally, SCFAs activated colonic NLRP6 inflammasome and increased DCX+ newborn neurons in the hippocampal DG of control mice. CONCLUSIONS: Our findings reveal that gut dysbiosis is a critical factor for a high-fructose diet-induced hippocampal neuroinflammation in C57BL/6N mice possibly mediated by impairing intestinal epithelial barrier. Mechanistically, the defective colonic NLRP6 inflammasome is responsible for intestinal epithelial barrier impairment. SCFAs can stimulate NLRP6 inflammasome and ameliorate the impairment of intestinal epithelial barrier, resulting in the protection against a high-fructose diet-induced hippocampal neuroinflammation and neuronal loss. This study addresses a gap in the understanding of neuronal injury associated with Western-style diets. A new intervention strategy for reducing the risk of neurodegenerative diseases through SCFAs supplementation or dietary fiber consumption is emphasized.

Prognostic value of long noncoding RNA ROR in patients with cancer in China: A systematic review and meta-analysis.

BACKGROUND: For cancer, it is common that there is usually a dysregulation of the long noncoding RNA regulator of reprogramming (LncRNA ROR). To illustrate the application of LncRNA ROR, which serves as the prognostic marker for the malignant tumors, it is of great importance to conduct a meta-analysis. METHODS: There were 3 databases being applied. The data used were collected before January 5, 2018. These 3 databases include the OVID, PubMed, and Science databse. To further explore the association between the expression and survival of LncRNA ROR, it calculated the 95% confidence intervals (CIs) and hazard ratios (HRs). Meanwhile, the odds ratios (ORs) have been calculated for the evaluation of the correlation between the pathological and expression parameters of LncRNA ROR. RESULTS: There were 8 researches participated by 720 patients. According to the HR, it has been implied that there was a high LncRNA ROR expression related with the weak disease-free survival (DFS) (HR = 3.48, 95% CI, 2.24-5.41) and overall survival (OS) (HR = 2.47, 95% CI, 1.76-3.47) among the cancer patients with none dramatic heterogeneity. There was also a correlation among lymph node metastasis (OR = 5.38, 95% CI, 2.21-13.12), high tumor stage (OR = 3.80, 95% CI, 1.95-7.41), and larger tumor size (OR = 4.43, 95% CI, 1.26-15.51). CONCLUSIONS: Thus, it can be predicted about the lymph node metastasis and high tumor stage, larger tumor size, DFS, and poor OS based on the high LncRNA ROR. This suggests that high LncRNA ROR can be used as a new indicator of poor prognosis in cancer.

Regulatory T cells may play a protection role in postoperative pulmonary dysfunction in rheumatic heart disease.

BACKGROUND: Postoperative pulmonary dysfunction (PPD) is a common complication observed in patients after cardiac surgery with cardiopulmonary bypass (CPB). The underlying mechanism regulating lung injury after CPB is unclear. However, since the involvement of regulatory T (Treg) cells and T helper 17 (Th17) cells in immune responses has been well established, in this study, we investigated the contribution of these lymphocyte subsets to the development of PPD after CPB. METHODS: Fifty-six rheumatic heart disease (RHD) patients' blood samples were collected at different time points before and after surgery. The samples were analyzed by flow cytometry to quantify cells and by enzyme-linked immunosorbent assay (ELISA) to measure the cytokine content. In addition, the inhibitory function of Treg cells of ten patients was tested before and after surgery. RESULTS: We showed that a decreased percentage of Treg cells and reduced Treg/Th17 ratio before anesthesia and after neutralization are meaningful predictors of severe PPD (AUC 0.722, 95% CI: 0.557 to 0.888; 0.787, 95% CI: 0.639 to 0.934; 0.751, 95% CI: 0.593 to 0.919; 0.551, 95% CI: 0.366 to 0.735). Interestingly, both the percentage of Treg cells and their suppressive effect on effector T lymphocyte (Teff) cells were increased after CPB, and both effects may play a protective role in PPD. By contrast, severe PPD was associated with increased IL-17A levels. CONCLUSIONS: The increased proportion of Treg cells in the CD4+ T cell population and higher ratio of Treg/Th17 before anesthesia induction and 30 min after heparin neutralization can partially protect patients from a severe inflammatory response and PPD.

An unusual case of aggressive systemic mastocytosis mimicking hepatic cirrhosis.

Hepatic involvement in aggressive systemic mastocytosis (ASM) is relatively common, and the main clinical features of this disease include hepatomegaly, portal hypertension, ascites, and fibrosis. Cirrhosis is a rare ASM symptom. We report an ASM case that initially mimicked cirrhosis based on clinical and radiographic analyses. The portal tract was expanded by mononuclear inflammatory cells, and an increase in collagen amount was observed in routine histological sections of the biopsied liver. A diagnosis of systemic mastocytosis (SM) was made after ancillary tests for mast cells using bone marrow aspirates. Extensive involvement of the liver and gastrointestinal tract was observed. Clinicians and pathologists need to consider ASM as a diagnosis or differential diagnosis in a clinical case of cirrhosis with unknown etiology. The diagnosis can be confirmed or disregarded by immunohistochemical staining and molecular analysis.

Application of triangular vector to functionally reconstruct the medial collateral ligament with double-bundle allograft technique.

PURPOSE: The purpose of this study was to present a novel medial collateral ligament (MCL) reconstruction technique and investigate the clinical outcomes of this surgical procedure. METHODS: From July 2006 to June 2009, 56 patients with medial instability of the knee were treated with MCL reconstruction and followed up for 33 months on average. These patients were divided into 2 groups based on whether anterior cruciate ligament (ACL) injury was present: 27 patients had isolated MCL injury, whereas 29 patients had combined MCL-ACL injury. All patients underwent reconstruction of the MCL with triangular double-bundle allograft, and we evaluated International Knee Documentation Committee (IKDC) scores, anteromedial rotatory instability (AMRI), and excessive knee medial opening (EKMO) both preoperatively and at follow-up. RESULTS: EKMO was significantly reduced to 2.9 mm at follow-up compared with 10.1 mm preoperatively. The incidence of AMRI was reduced to 9.4% (5 patients) compared with 67.9% (36 patients) preoperatively. Of the patients, 58.9% (33 patients) had a grade A IKDC subjective score and 35.7% (20 patients) had a grade B IKDC subjective score. Most patients had normal or nearly normal range of motion of the knee joint, whereas 4 patients (7.1%) lost more than 6° of range of motion in extension and 2 (3.6%) lost more than 25° in flexion. In 47 patients (83.9%) the symptoms were graded as normal or nearly normal according to IKDC symptom scores. No significant differences in IKDC subjective score, IKDC symptom score, flexion deficit score, AMRI, and EKMO were found between the isolated MCL injury group and the MCL-ACL injury group; however, a significant difference was found in knee extension deficit between groups. CONCLUSIONS: We have presented a new technique for reconstruction of the MCL with a triangular shape. This technique improved both valgus and rotational stability at short-term outcome. The clinical outcomes using IKDC evaluation indicate that no major difference exists in isolated MCL injury and combined MCL-ACL injury treated with this new technique. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Autophagy enhances the aggressiveness of human colorectal cancer cells and their ability to adapt to apoptotic stimulus.

OBJECTIVE: To investigate LC3B-II and active caspase-3 expression in human colorectal cancer to elucidate the role of autophagy, and to explore the relationship of autophagy with apoptosis in human colorectal cancer. METHODS: LC3B expression was detected by immunohistochemistry in 53 human colorectal cancer tissues and 20 normal colon tissues. The protein levels of LC3B-II and active caspase-3 were also determined by Western blot analysis in 23 human colorectal cancer tissues and 10 normal colon tissues. RESULTS: LC3B was expressed both in cancer cells and normal epithelial cells. LC3B expression in the peripheral area of cancer tissues was correlated with several clinicopathological factors, including tumor differentiation (P=0.002), growth pattern of the tumor margin (P=0.028), pN (P=0.002), pStage (P=0.032), as well as vessel and nerve plexus invasion (P=0.002). The protein level of LC3B-II in cancer tissue was significantly higher than in normal tissue (P=0.038), but the expression of active forms of procaspase-3 in cancer tissue was lower (P=0.041). There was a statistically significant positive correlation between the expression levels of LC3B-II and the active forms of procaspase-3 (r=0.537, P=0.008). CONCLUSIONS: Autophagy has a prosurvival role in human colorectal cancer. Autophagy enhances the aggressiveness of colorectal cancer cells and their ability to adapt to apoptotic stimulus.

[Arthroscopic single-bundle anterior cruciate ligament reconstruction with six-strand hamstring tendon and patellar tendon allograft].

OBJECTIVE: To compare the outcome of arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction with six-strand hamstring tendon and patellar tendon allograft. METHODS: From October 2006 to December 2009, 108 patients with arthroscopic single-bundle ACL reconstruction were retrospectively reviewed, with 58 patients with six-strand hamstring tendon (Group H), and 50 patients with patellar tendon allograft (Group P). Patients were available for clinical evaluation with KT-1000 arthrometer measurements, Lachman and pivot-shift test, and knee function with the International Knee Documentation Committee (IKDC), Lysholm scores. RESULTS: All the patients were followed up at an average of 28.6 months (range 12 - 38 months). The average side-to-side difference was lesser for group H (1.2 ± 1.2) mm than group P (1.8 ± 1.5) mm (P < 0.05). On the pivot-shift test, 55 (94.8%) patients were negative and 3 (5.2%) were positive in group H, whereas 41 (82.0%) were negative and 9 (18.0%) were positive in group P, with significant difference between two groups (P < 0.05). All knee function scores were improved postoperatively, without statistically significant difference between the two groups (P > 0.05). CONCLUSION: Arthroscopic single-bundle ACL reconstruction with six-strand hamstring tendon will achieve better knee stability than patellar tendon allograft.

[Relationship between genetic polymorphism of ERCC1 and susceptibility to liver cancer].

OBJECTIVE: To investigate the association between genetic polymorphisms of ERCC1-C8092A and susceptibility to liver cancer, as well as the gene-environmental interaction on the etiology of liver cancer in Fuzhou. METHODS: A case-control study was conducted to collect the information on environmental exposure while genetic polymorphism of ERCC1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. General relative risk regression models were further applied to fit the interaction between genetic polymorphisms of ERCC1-C8092A and the environmental factors of liver cancer. RESULTS: ERCC1-C8092A variant genotypes were associated with significant increasing risk of liver cancer adjusted odds ratio (OR = 3.789, 95%CI: 2.792 - 5.142), compared to the wild-type homozygote. Data from the analysis of interaction showed that genetic polymorphism of ERCC1-8092A appeared super-additive interaction with drinking pond-ditch or with hepatitis B, and super-multiplicative interaction with eating moldy food. CONCLUSION: The point mutation in ERCC1-8092A was possibly susceptible to liver cancer, and related synergistically with other risk factors in hepatocelluar carcinogenesis in Fuzhou.

[Anterior cruciate ligament reconstruction using periosteum wrapped autologous hamstring tendons: clinical research].

OBJECTIVE: To develop a surgical technique using a periosteal flap wrapped autologous hamstring tendons in ACL reconstruction and to examine its short-term outcome. METHODS: A total of 110 patients (110 knees) were included. The experimental group (n = 52) received ACL reconstruction with hamstring tendons wrapped in periosteum. In the other 58 patients, ACL was reconstructed with autologous hamstring tendons. The mean post-operative follow-up was 19 (12 - 25) months. All patients were assessed at 12 months post-operation. The parameters of efficacy evaluation included IKDC score, Tegner score, modified HSS score, KT-1000 arthrometer reading and a radiographic assessment using anteroposterior and lateral radiographs. The incidence of femoral and tibial bone tunnel enlargement between two groups was compared with chi(2) test. RESULTS: Clinical outcomes in experimental group (periosteum-wrapped grafts) were dependent on the wrap-up of periosteum, bone tunnel, graft fixation and postoperative rehabilitation. The good or excellent outcomes were reported in approximately 90% of the experimental group. And 44 patients showed normal or nearly normal knee function according to IKDC criteria. KT-1000 tests showed an average maximal manual side-to-side difference of 1.7 +/- 1.1 mm. Forty patients showed the outcomes of KT-1000, Lachman's knee ligament test and pivot-shift testing. The evaluation of the level of activity using the Tegner score revealed that 40 patients regained their pre-injury activity level. And 44 patients showed full knee extension and 42 patients showed full knee flexion after surgery. The average HSS score showed no significant difference between experimental group (90.6 +/- 0.57 points) and control group (89.9 +/- 0.8 points) (t = 0.714, P > 0.05). The KT-1000 measurement (133N) was larger in control group (2.3 +/- 1.0 mm) than in experimental group (1.7 +/- 1.1 mm). There was significant difference in laxity between two groups (t = 6.427, P < 0.05). At 12 months post-operation, tunnel enlargement could be observed in both groups. The average enlargement of femoral tunnel was less in experimental group (17.3%) than control group (34.5%) (chi(2) = 4.17, P < 0.05). And the enlargement of tibial tunnel was less in experimental group (19.2%) than control group (36.2%) (chi(2) = 3.90, P < 0.05). CONCLUSIONS: The surgical technique using a periosteal flap wrapped with autologous hamstring tendons in ACL reconstruction has definite clinical efficacies. It can enhance the stability of knee and prevent the enlargement of bone tunnel.