DNA and histone modifications as potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.

Lung cancer has a very high mortality in females and males. Most (~ 85%) of lung cancers are non-small cell lung cancers (NSCLC). When lung cancer is diagnosed, most of them have either local or distant metastasis, with a poor prognosis. In order to achieve better outcomes, it is imperative to identify the molecular signature based on genetic and epigenetic variations for different NSCLC subgroups. We hypothesize that DNA and histone modifications play significant roles in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Epigenetics has a significant impact on tumorigenicity, tumor heterogeneity, and tumor resistance to chemotherapy, targeted therapy, and immunotherapy. An increasing interest is that epigenomic regulation is recognized as a potential treatment option for NSCLC. Most attention has been paid to the epigenetic alteration patterns of DNA and histones. This article aims to review the roles DNA and histone modifications play in tumorigenesis, early detection and diagnosis, and advancements and therapies of NSCLC, and also explore the connection between DNA and histone modifications and PPPM, which may provide an important contribution to improve the prognosis of NSCLC. We found that the success of targeting DNA and histone modifications is limited in the clinic, and how to combine the therapies to improve patient outcomes is necessary in further studies, especially for predictive diagnostics, targeted prevention, and personalization of medical services in the 3P medicine approach. It is concluded that DNA and histone modifications are potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.

[Mid- and long-term effectiveness analysis of distraction arthroplasty in treatment of moderate to severe ankle arthritis].

Objective: To investigate the mid- and long-term effectiveness of external fixator distraction arthroplasty in the treatment of moderate to severe ankle arthritis. Methods: The clinical data of 23 patients with moderate to severe ankle arthritis treated with external fixation distraction arthroplasty who met the selection criteria between January 2007 and November 2019 were retrospectively analyzed. There were 20 males and 3 females; the age ranged from 21 to 65 years, with an average age of 43.7 years. Etiology included 8 cases of primary ankle arthritis, in which 5 cases combined with varus deformity; 15 cases of traumatic ankle arthritis, the cause of injury was 5 cases after ankle fracture surgery, 3 cases after Pilon fracture surgery, 5 cases of chronic ankle instability and repeated sprain, and 2 cases of other causes. According to Takakura staging system, there were 4 cases of stage ⅢA, 12 cases of stage ⅢB, and 7 cases of stage Ⅳ; according to Giannini staging system, there were 5 cases of stage Ⅱ and 18 cases of stage Ⅲ; according to Cheng staging system, 16 cases were in stage Ⅲ, and 7 cases stage Ⅳ. American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) score were used to evaluate the improvement of ankle pain and function before operation and at last follow-up, and the data were analyzed according to different etiological groups. At last follow-up, the surgical results were evaluated subjectively and objectively. The changes of ankle joint space before operation and at last follow-up were compared. The patients were divided into two groups according to their age: ≤45 years old group [young group, 10 cases, aged (35.62±7.41) years old] and >45 years old group [middle-aged and elderly group, 13 cases, aged (54.20±6.20) years old]. The AOFAS ankle-hindfoot score and VAS score were compared before and after operation between the two groups, and the influence of age on distraction arthroplasty was analyzed. Results: The external fixator was removed after 3 months of continuous distraction,12 patients got infection around the wire tunnels. All the 23 patients were followed up 13-143 months, with an average of 56.9 months; the follow-up time was (43.46±32.77) months and (69.80±37.79) months in the young group and middle-aged and elderly group, respectively. At last follow-up, the AOFAS ankle-hindfoot score and VAS score significantly improved when compared with those before operation ( P<0.05). According to etiological analysis, there was no significant difference in AOFAS ankle-hindfoot score and VAS score before and after operation ( P>0.05) in Pilon fracture patients, while the significant difference was found in remaining patients ( P<0.05). There was significant difference in AOFAS ankle-hindfoot score before operation between the young group and the middle-aged and elderly group ( t=2.110, P=0.040), but no significant difference in preoperative VAS score and the differences in VAS score and AOFAS ankle-hindfoot score before and after operation between the two groups ( P>0.05). The subjective and objective results of pain evaluation at last follow-up showed that 4 patients had no pain, 12 patients had moderate pain relief, 5 patients had mild pain relief, and 2 patients had no significant pain relief; among the 10 patients who were followed up more than 5 years, there were 2, 5, 2, and 1 patient, respectively; 2 patients who were followed up more than 10 years had moderate pain relief. At last follow-up, the ankle joint space was (3.7±0.4) mm, which significantly increased when compared with before operation [(1.5±0.2) mm] ( t=1.791, P=0.002). The ankle joint space was (2.9±0.5) mm in 10 patients who were followed up more than 5 years, and 3.3 mm and 3.0 mm in 2 patients who were followed up more than 10 years. Conclusion: Distraction arthroplasty of the ankle joint can achieve satisfactory results in patients with moderate to severe ankle arthritis (except for arthritis caused by Pilon fracture), and age has no significant effect on distraction arthroplasty.

[Application of posterior median longitudinal W-shaped incision combined with layer-by-layer combing suture in acute closed Achilles tendon rupture].

OBJECTIVE: To explore the effectiveness of posterior median longitudinal W-shaped incision combined with layer-by-layer combing suture in the treatment of acute closed Achilles tendon rupture. METHODS: The clinical data of 32 patients with acute closed Achilles tendon rupture who met the selection criteria between August 2015 and February 2019 were retrospectively analyzed. There were 25 males and 7 females, with an average age of 33 years (range, 21-48 years). All of them were closed rupture of Achilles tendon caused by sports injury. Physical examination on admission: the rupture space of Achilles tendon was palpable; Thompson sign was positive; the rupture of Achilles tendon was confirmed by MRI and ultrasonography before operation, the distance between the broken end and the insertion point of Achilles tendon was 2-8 cm, with an average of 3.5 cm. The average time from injury to operation was 2.7 days (range, 1-10 days). During the operation, the posterior median longitudinal W-shaped incision of Achilles tendon was used to expose the broken end of Achilles tendon, and the deep and shallow double Kessler end-to-end suture+layer-by-layer combing suture were used to suture the Achilles tendon, and the skin incision was sutured by "V-Y"advancement. The postoperative complications were observed; the healing of Achilles tendon was observed by ultrasonography; at last follow-up, Arner Lindholm criteria was used to evaluate ankle function. RESULTS: The 32 patients were followed up 8-24 months, with an average of 12 months. The incision healed by first intention, without the complications of skin necrosis, nonunion, delayed healing, and infection, scar hyperplasia or ulcer, and symptom of peroneal nerve injury. No Achilles tendon rupture and deep infection occurred during the follow-up period. The ultrasonography examination showed that the Achilles tendon was healing. At last follow-up, according to Amer Lindholm evaluation standard, the results of ankle function was excellent in 26 cases and good in 6 cases. CONCLUSION: The treatment of acute closed Achilles tendon rupture with a posterior median longitudinal W-shaped incision combined with deep and shallow double Kessler end-to-end suture+layer-by-layer combing suture is effective, which can fully exposed the incision, the quality of Achilles tendon anastomosis is reliable, and it can effectively avoid wound complications and iatrogenic injury of gastrocnemius nerve.

[Repair of limb wounds with free profunda artery perforator flap in posteromedial femoral region].

OBJECTIVE: To explore the effectiveness of free profounda artery perforator flap (PAPF) in the posteromedial femoral region for the treatment of traumatic skin defects of limbs. METHODS: Between March 2015 and April 2017, 11 cases of traumatic limb skin defect with deep tissue exposure were treated with free PAPF in posteromedial femoral region. There were 7 males and 4 females, with an average age of 39 years (range, 26-54 years). There were 4 cases of upper limb skin defect and 7 cases of lower limb skin defect. The causes of injury included 6 cases of traffic accident injury, 3 cases of machine crush injury, and 2 cases of crush injury. The size of wounds ranged from 11 cm×7 cm to 18 cm×11 cm. The time from post-traumatic admission to flap repair were 4-9 days (mean, 7.3 days). The size of free PAPF ranged from 15 cm×9 cm to 22 cm×13 cm. The donor site of 8 cases were closed directly; 3 cases could not be closed directly, and skin grafting was used to cover the wound. RESULTS: The time of skin flap harvest was 40-90 minutes (mean, 47 minutes). All flaps and skin grafts survived and the wounds healed by first intention. All the 11 patients were followed up 6-19 months (mean, 12 months). The skin flaps were soft in texture, similar in color to the skin around the injured limbs, without obvious pigmentation and hair overgrowth. Three of them underwent second-stage skin flap thinning. At last follow-up, the limb function of all patients recovered well. Longitudinal scar could be seen in the donor site of the flap, and the location was concealed. All patients did not complain that scar of the donor site affected their sexual life during the follow-up. CONCLUSION: Free PAPF can achieve satisfactory results in repairing skin defects of extremities. The flaps have the advantages including constant perforator branches, simple operation, and concealed donor site.