A middle lobe sparing sleeve resection versus bilobectomy for right lower central non-small cell lung cancer: a retrospective propensity score matched cohort study.

OBJECTIVES: The right lower sleeve lobectomy is a rarely performed major lung resection.This study aims to evaluate the safety and effectiveness of this procedure by comparing to right lower bilobectomy in non-small cell lung cancer patients. METHODS: We retrospectively reviewed a prospective database of non-small cell lung cancer patients who underwent right lower sleeve lobectomy (group S) or right lower bilobectomy (group B) from January 2014 to January 2020 in Shanghai Pulmonary Hospital. Propensity score matching method was applied to balance confounders between the two groups, resulting in 41 matched pairs.The analysis was performed to compare perioperative outcomes, long-term survival, and postoperative pulmonary volume between the two groups. RESULTS: No significant differences in the characteristics were observed between the two matched groups.Major postoperative complications developed in 31.7% of the patients in group B and 12.1% of the patients in group S (P = 0.032).Intervention rate for surgical residual cavity in group B is significantly higher than those patients in group S(21.9%vs7.3%,p = 0.037).The postoperative right lateral and overall lung volume in group S were both significantly larger than that in group B (P = 0.026,P = 0.001,respectively). CONCLUSIONS: Compared to bi-lobectomy, a middle lobe sparing sleeve resection obtains a less prevalence of major complications, smaller postoperative residual air space and similar long-term survival for selected central right lower NSCLC patients.

Characteristics of the paravertebral muscle in adult degenerative scoliosis with PI-LL match or mismatch and risk factors for PI-LL mismatch.

Objective: Pelvic incidence (PI) minus the lumbar lordosis (LL) angle (PI-LL) correlates with function and disability. It is associated with paravertebral muscle (PVM) degeneration and is a valuable tool for surgical planning of adult degenerative scoliosis (ADS). This study aims to explore the characteristics of PVM in ADS with PI-LL match or mismatch and to identify the risk factors for PI-LL mismatch. Methods: A total of 67 patients with ADS were divided into PI-LL match and mismatch groups. The visual analog scale (VAS), symptom duration, and Oswestry disability index (ODI) were used to assess patients' clinical symptoms and quality of life. The percentage of fat infiltration area (FIA%) of the multifidus muscle at the L1-S1 disc level was measured by using MRI with Image-J software. Sagittal vertical axis, LL, pelvic tilt (PT), PI, sacral slope, and the asymmetric and average degeneration degree of the multifidus were recorded. Logistic regression analysis was done to identify the risk factors for PI-LL mismatch. Results: In the PI-LL match and mismatch groups, the average FIA% of the multifidus on the convex side was less than that on the concave side (P < 0.05). There was no statistical difference of asymmetric degeneration degree of the multifidus between the two groups (P > 0.05). In the PI-LL mismatch group, the average degeneration degree of the multifidus, VAS, symptom duration, and ODI were significantly higher than that in the PI-LL match group, respectively (32.22 ± 6.98 vs. 26.28 ± 6.23 (%), 4.33 ± 1.60 vs. 3.52 ± 1.46, 10.81 ± 4.83 vs. 6.58 ± 4.23 (month), 21.06 ± 12.58 vs. 12.97 ± 6.49, P < 0.05). The average degeneration degree of the multifidus muscle was positively correlated with the VAS, symptom duration, and ODI, respectively (r = 0.515, 0.614, and 0.548, P < 0.05). Sagittal plane balance, LL, PT, and the average degeneration degree of the multifidus were the risk factors for PI-LL mismatch (OR: 15.447, 95% CI: 1.274-187.269; OR: 0.001, 95% CI: 0.000-0.099; OR: 107.540, 95% CI: 5.195-2,225.975; OR: 52.531, 95% CI: 1.797-1,535.551, P < 0.05). Conclusion: The PVM on the concave side was larger than that on the convex side in ADS irrespective of whether PI-LL matched or not. PI-LL mismatch could aggravate this abnormal change, which is an important cause of pain and disability in ADS. Sagittal plane imbalance, decreased LL, higher PT, and larger average degeneration degree of the multifidus were independent risk factors for PI-LL mismatch.

Role of miR-199a-5p in osteoblast differentiation by targeting TET2.

OBJECTIVE: miR-199a-5p was increased during osteoblast differentiation, which may target and regulate TET2, a gene attracted a lot of attention in the osteoblast differentiation in the past few years. However, the role of miR-199a-5p in osteoblast differentiation by targeting TET2 is not established. METHODS: The correlation between miR-199a-5p and TET2 was verified through dual luciferase reporter assay, and their expressions in human bone marrow stromal cells (hBMSCs) during the osteoblast differentiation were detected. hBMSCs were transfected with TET2 siRNA, miR-199a-5p mimic or/and TET2 CRISPR activation plasmid., and then prepared for the induction of osteoblast differentiation, followed by alkaline phosphatase (ALP) and alizarin red staining, qRT-PCR and Western blotting. In vivo, ovariectomized (OVX) mice were injected with agomir-miR-199a-5p, antagomiR-199a-5p or/and TET2 siRNA to calculate the BMD and BV/TV ratio of mice, as well as to measure the expressions of osteogenesis-related genes in bone tissues. RESULTS: A gradual increase of miR-199a-5p was observed in hBMSCs during the induction of osteoblast differentiation, while TET2 expression was decreased. Besides, miR-199a-5p was reduced in the bone tissue of OVX mice, while TET2 was up-regulated. In addition, overexpression of miR-199a-5p and inhibition of TET2 augmented ALP activity in hBMSCs, with the enhanced calcification and the up-regulated expressions of Runx2, OSX and OCN, which also increased the quality of bone in OVX mice accompanying the enhancement BV/TV ratio, BMD and osteogenesis-related genes. CONCLUSION: MiR-199a-5p may promote the osteoblast differentiation and prevent OVX-induced osteoporosis by targeting TET2.

CCL28 promotes locomotor recovery after spinal cord injury via recruiting regulatory T cells.

BACKGROUND: Chemokines play a key role in post-traumatic inflammation and secondary injury after spinal cord injury (SCI). CCL28, the chemokine CC-chemokine ligand 28, is involved in the epithelial and mucosal immunity. However, whether CCL28 participates in the physiopathologic processes after SCI remains unclear. RESULTS: CCL28 is upregulated in the spinal cord after SCI. In addition, neutralizing antibodies against IL-1ß or TNF-α, or treatment of ML120B, a selective inhibitor of IKK-ß, remarkably decrease CCL28 upregulation, suggesting that CCL28 upregulation relies on NF-κB pathway activated by IL-1ß and TNF-α after SCI. Moreover, CD4+CD25+FOXP3+ regulatory T (Treg) cells that express CCR10, a receptor of CCL28, are enriched in the spinal cord after SCI. We further demonstrate that the spinal cord recruits Treg cells through CCL28-CCR10 axis, which in turn function to suppress immune response and promote locomotor recovery after SCI. In contrast, neutralizing CCL28 or CCR10 reduces Treg cell recruitment and delays locomotor recovery. METHODS: The neutralizing antibodies and recombinant CCL28 were injected intraspinally into the mice prior to SCI, which was established via hemitransection. RT-qPCR analysis was performed to determine transcript level, and Western blot analysis and ELISA assay were used to detect protein expression. Immune cells were analyzed by flow cytometry and visualized by immunofluorescence. The chemotaxis was assessed by in vitro transwell migration assay. The mouse locomotor activity was assessed via the Basso Mouse Scale (BMS) system. CONCLUSIONS: These results indicate that NF-κB pathway-regulated CCL28 production plays a protective role after SCI through recruiting CCR10-expressing and immunosuppressive Treg cells, and suggest that interfering CCL28-CCR10 axis might be of potential clinical benefit in improving SCI recovery.

MiR-202-5p/PTEN mediates doxorubicin-resistance of breast cancer cells via PI3K/Akt signaling pathway.

We intended to explore the effect of miR-202-5p and phosphatase and tensin homolog (PTEN) on doxorubicin (DOX) resistance of breast cancer cells. The result of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) reveals that miR-202-5p was highly expressed in drug-resistant breast cancer tissues, while PTEN was expressed less. MiR-202-5p directly targeted PTEN. Further, it was found that the overexpression of miR-202-5p promoted the DOX resistance and proliferation as well as decreased apoptosis of MCF-7 cells. The lower expression of miR-202-5p inhibited DOX resistance and proliferation as well as increased the apoptosis of MCF-7/DOX cells. In vivo experiments showed that mice with downregulated miR-202-5p had smaller tumor volume and lower Ki67 level. The overexpression of PTEN declined the proliferation of MCF7 cells, while miR-202-5p's overexpression could offset the function of overexpression of PTEN. The knockdown of PTEN promoted MCF7/DOX cell proliferation that could be counteracted by miR-202-5p silence. Moreover, we also revealed that downregulated miR-202-5p expression inhibited PI3k/Akt signaling pathway-related protein by regulating expression of PTEN.

NCOA3 Loss Disrupts Molecular Signature of Chondrocytes and Promotes Posttraumatic Osteoarthritis Progression.

BACKGROUND/AIMS: Osteoarthritis (OA) is the most common joint disease. Recently, a novel variant near the nuclear receptor coactivator 3 (NCOA3) has been identified in association with greater risk of developing OA. However, how NCOA3 is regulated in chondrocytes and involved in OA pathogenesis remain elusive. METHODS: The expression and DNA methylation of NCOA3 in knee OA cartilage and in vitro dedifferentiated chondrocytes with or without rs6094710 SNP were analyzed by qRT-PCR, immunoblotting, methylation-specific PCR and bisulfite sequencing. NCOA3 was depleted by siRNA or shRNA or inhibited by a chemical inhibitor to assess its role in chondrocyte dedifferentiation or OA pathogenesis in posttraumatic OA animal model established by cruciate ligament transection surgery. RESULTS: We found that compared with normal counterparts, samples with rs6094710 SNP failed to upregulate NCOA3. Further evidence associated this phenotype with DNMT1-mediated hypermethylation in gene promoter region. Moreover, we showed that NCOA3 maintained the molecular signature of chondrocytes dedifferentiating in vitro or exposed to IL-1ß, nevertheless, NCOA3 appeared dispensable for preventing OA initiation, since NCOA3 loss did not trigger OA in young mice. Instead, NCOA3 loss promoted posttraumatic OA progression, and in parallel, enhanced NF-κB activation. Finally, the promoted posttraumatic OA progression was significantly retarded when administrated with NF-κB pathway inhibitor, suggesting that NCOA3 lose promotes posttraumatic OA at least partially by enhancing NF-κB activation. CONCLUSION: Thus, our findings indicate a critical role of NCOA3 in chondrocytes, and imply that manipulating NCOA3 might present a potential therapeutic approach to interfere OA progression.

Effects of sealing the intramedullary femoral canal in total knee arthroplasty: A randomized study.

BACKGROUND: This study investigates the clinical effects of sealing the femoral canal by intramedullary alignment instrumentation in total knee arthroplasty (TKA). METHODS: One hundred twenty consecutive patients with knee osteoarthritis, who underwent unilateral TKA, were enrolled in the study and equally randomized into 2 groups: the sealing group and the control group. In the sealing group, the femoral canal was sealed with autogenous bone and cement using intramedullary alignment instrumentation, while the femoral hole was left open for patients in the control group. Blood loss, hemoglobin (Hb) reduction, and other parameters were recorded, as well as the duration of hospital stay and complications. The Hospital for Special Surgery (HSS) knee score was used to assess knee function at the final follow-up appointment. RESULTS: The calculated blood loss, hidden blood loss, transfusion requirements, drainage volume, and Hb reduction measurements were significantly different (P < .05) between the 2 groups. There were no significant differences in the surgery time, intraoperative blood loss, length of hospital stay, HSS score or complications between the 2 groups (P > .05). CONCLUSIONS: Sealing the intramedullary canal with autologous bone and a cement plug is an effective method for reducing blood loss and decreasing blood transfusion requirements during TKA procedures that have increasing complication rates.

Dimethyl sulfoxide damages mitochondrial integrity and membrane potential in cultured astrocytes.

Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO.