The Role of m6A-Mediated DNA Damage Repair in Tumor Development and Chemoradiotherapy Resistance.

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.

[Research progress of mechanisms of acupuncture in treating slow transit constipation].

As an important part of the traditional Chinese medicine treatment system, acupuncture therapy has been used in the treatment of slow transit constipation (STC) for a long time and has achieved good clinical effects. This article reviews research on the effects of acupuncture therapy on STC published in recent years, focusing on the mechanism of acupuncture on the enteric nervous system, neurotransmitters, interstitial cells of Cajal, smooth muscle cells, gastrointestinal motility, psychological factors and intestinal microecology of STC, in order to provide reference for the clinical application and mechanism research of acupuncture in the treatment of STC in the future.

Interaction Tolerance Detection Test for Understanding the Killing Efficacy of Directional Antibiotic Combinations.

Combination treatments are commonly prescribed for enhancing drug efficacy, as well as for preventing the evolution of resistance. The interaction between drugs is typically evaluated near the MIC, using growth rate as a measure of treatment efficacy. However, for infections in which the killing activity of the treatment is important, measurements far above the MIC are needed. In this regime, the killing rate often becomes weakly concentration dependent, and a different metric is needed to characterize drug interactions. We evaluate the interaction metric on killing using an easy visual assay, the interaction tolerance detection test (iTDtest), that estimates the survival of bacteria under antibiotic combinations. We identify antibiotic combinations that enable the eradication of tolerant bacteria. Furthermore, the visualization of the antibiotic interactions reveals directional drug interactions and enables predicting high-order combination outcomes, therefore facilitating the determination of optimal treatments. IMPORTANCE The killing efficacy of antibiotic combinations is rarely measured in the clinical setting. However, in cases where the treatment is required to kill the infecting organism and not merely arrest its growth, the information on the killing efficacy is important, especially when tolerant strains are implicated. Here, we report on an easy method for the determination of the killing efficacy of antibiotic combinations which enabled to reveal combinations effective against tolerant bacteria. The results could be generally used to guide antimicrobial therapy in life-threatening infections.

The preservation and application of the submandibular gland in oral squamous cell carcinoma (STROBE).

This prospective study aimed to investigate metastases of oral squamous cell carcinoma (OSCC) to cervical lymph nodes and submandibular glands and to analyze the safety and feasibility of preserving and using submandibular glandular flaps to repair postoperative OSCC defects.Overall, 330 patients with OSCC who met the inclusion criteria were enrolled in the study from January 2014 to July 2018. OSCC metastasis to cervical lymph nodes and submandibular glands was investigated using intraoperative frozen section and postoperative pathological observation. Fifteen patients who underwent repair of postoperative OSCC defects with submandibular glandular flaps were monitored for postoperative wound healing, complications, pathology, and appearance satisfaction and were followed up long term.Among the 330 patients with OSCC, the most common type was tongue cancer (138/330); 204 patients were node negative and 126 were node positive. Of 363 samples of the submandibular gland, 7 were metastatic with stage IV lesion, 5 were directly invaded by the primary tumor, and 2 were metastatic with extranodal extension in level Ib. None of the submandibular gland samples showed intraglandular hematogenous and nodal metastases. The repair of OSCC defects with submandibular glandular flaps was successful in all 15 patients, including 11 males and 4 females, with an age range of 19-74 years and a mean of 51 years. Of 15 patients, some had complications with heart and cerebrovascular diseases, diabetes, or chronic respiratory disease. All the submandibular glandular flaps survived postoperatively without any complications, and the mucosification on the surface was adequate. Follow-ups (median duration: 14 months) revealed the satisfactory recovery of shape and function without any local recurrences or distant metastases.Direct invasion is the main form of OSCC metastasis to the submandibular gland, while hematogenous and nodal metastases are uncommon. Preservation of the submandibular gland is oncologically safe. Thus, repair of postoperative OSCC defects with submandibular gland flaps is a feasible and promising procedure.

Characterization of the dissociation kinetics of Cd and Ni in soils based on diffusive gradients in thin films technique.

A new theoretical method was established for the combinatorial calculation of the dissociation rate constant (K-1) of the metal-organic complexes (MLs), the concentration of free ionic soil metals (CM), the labile concentration of soil metal-organic complexes (CML) based on diffusive gradients in thin-films (DGT) technique with a range of diffusive layer thicknesses (0.053-0.173 mm) in soils. The fitting results agreed well with the determined values. The values of K-1, CML and CM were calculated without other morphological analysis software and the fitting results agreed well with the determined values with some advantages such as the use of fewer hypothetical parameters, ease of calculation, the full embodiment of the contribution of MLs to the labile content. According to the results of model fitting, cation exchange capacity and soil organic matter were found to be the key environmental factors for K-1 values of Cd and Ni, respectively. The labile contents of Cd and Ni in soil were closely related with pH, soil organic matter and the total contents of heavy metals.

The effect of nursing intervention on preoperative cataract.

This retrospective study investigated the effect of nursing intervention (NIV) in Chinese patients under preoperative cataract (PC). A total of 70 eligible patients with PC were included. Thirty-five patients in an intervention group received regular clinical treatment and NIV before the surgery, while the other 35 patients received regular clinical treatment only. The NIV was applied 4 sessions, 1 week before the surgery. The primary outcome of satisfaction was measured by 11-points visual analog scale. The secondary outcomes were measured by the functional impairment caused by cataract (the VF-14), cooperativeness during the surgery period, and sleep quality. All the outcome measurements were assessed before and after the surgery. After NIV, patients in the intervention group exerted better outcomes in decreasing anxiety (P < .01), increasing current experience with satisfaction (P < .01), and enhancing the cooperativeness during the surgery period (P < .01), compared to those outcomes in the control group. The results of this study showed that NIV may help increase satisfaction in experience and cooperation, and decrease anxiety in Chinese patients with PC.

[The significance of beta-receptor expression in infantile hemangiomas].

OBJECTIVE: To investigate the expression and significance of beta-receptor ( p-R) in infantile hemangioma. METHODS: The expression of beta-R was detected by immunohistochemistry in infantile hemangioma (40 cases), venous malformation (20 cases) and normal skin (10 cases). RESULTS: The positive expression rate of beta2-R was 70% (28/40) in infantile hemangioma, while no expression of beta2-R in venous malformation and normal skin. Among 28 cases with positive expression of beta2-R, 24 cases were in proliferative phase. The positive expression of beta2-R in infantile hemangioma was significantly higher than that in venous malformation and normal skin tissue. The positive expression of beta2-R in the proliferative hemangioma and non-proliferative hemangioma was also significantly different (P < 0.05). CONCLUSIONS: beta2-R is specifically expressed in infantile hemangioma, especially in proliferative hemangioma.

[Reduction mammaplasty with central gland pedicle based on Würinger's horizontal septum].

OBJECTIVE: To investigate the method and efficacy of reduction mammaplasty with central gland pedicle based on Würinger' s horizontal septum in the treatment of female breast hypertrophy. METHODS: From Mar. 2009 to Sept. 2011, a series of 21 consecutive patients with mild and moderate hypermastia underwent reduction mammaplasty with central gland pedicle. Only the mammary gland located at cranial portion of septum was resected and the mammary gland located at caudal portion of septum was preserved. RESULTS: In our series, the mean resection weight per breast was (327.8 +/- 148.6) g, the mean nipple-to clavicle midpoint was 20.0 cm (range, 18.0-22.0 cm) and the mean nipple-to-sternal-notch distance was 21.0 cm (range, 19.5-22.5 cm) postoperatively. Nipple was moved upward 6.5 cm on average (range, 4.0-10.0 cm). There was no hematoma and nipple-areolar complex (NAC) necrosis. Minimal wound dehiscence occurred in one case and healed by dressing change. 17 cases were followed up for 3 months to 2 years. Satisfactory breast shape was achieved with good NAC sensibility. CONCLUSIONS: The reduction mammaplasty with central gland pedicle based on Würinger' s horizontal septum is a safe and reliable technique for mild and moderate hypermastia. Satisfactory breast contour, as well as NAC viability and sensibility, could be achieved with lower occurrence of hematoma or seroma.

[Auricular reconstruction by soft tissue expansion techniques without skin grafting].

OBJECTIVE: To investigate a method of auricular reconstruction by soft tissue expansion techniques without skin grafting. METHODS: Two tissue expanders (50 ml and 70 ml) were implanted under the skin of mastoid in 15 patients with grade II or III microtia. One big expander (100 ml) were implanted under the skin of mastoid in 13 patients with grade I microtia and 3 patients with grade II or III microtia. After skin expansion, the expanders were taken out. The autologous rib cartilage or Medpor scaffolds were implanted. The superior expanded skin flap was used to cover the frontal surface and the upper part of the back surface of the framework. The inferior expanded skin flap was transplanted to cover the lower part of the back surface of the framework. The remained expanded skin flap was transplanted to cover the wound in the lateral of head. RESULTS: No skin graft was needed in all the patients. Epidermis blister occurred at the distal part of flap in one case. No other complication was happened. A follow-up of 6 to 12 months (mean 10.9 months) was carried out in all patients with good cosmetic result when the reconstructed ear underwent second-stage operation. The scar size on the dornor site was (5.2 +/- 0.6) cm2 The satisfactory rate was 90% (28/31). CONCLUSIONS: The expanded skin with this new method is enough for auricular reconstruction without skin grafting, leaving less complication and less scar at donor site.

[Auricular reconstruction and correction of mild hemifacial microsomia with dermal fat graft in one stage].

OBJECTIVE: To evaluate the effect of auricular reconstruction and correction of mild hemifacial microsomia with dermal fat graft in one stage. METHODS: 28 cases with microtia and grade I and II hemifacial microsomia were treated. The tissue expander was implanted under the skin of mastoid at the first stage. At the second stage, the auricular reconstruction was performed with autologous rib cartilage framework. The remained dermal fat tissue from the donor site was inserted subcutaneously to correct the asymmetric face of microsomia. 20 cases, who underwent auricular reconstruction only, were used as control group. RESULTS: The facial asymmetry was greatly improved after operation in the 28 cases. The complications happened in 7% (2/28) of the patients, including one case of infection and one case of framework exposure. While it was 5% (1/20) in control group, showing no significant difference between the two groups (P > 0.05). The satisfactory rate was 93% (26/28) in one-staged group and 80% (16/20) in control group (P < 0.05). CONCLUSIONS: The dermal fat graft which should be abandoned in the traditional auricular reconstructions could be used to correct mild hemifacial microsomia with satisfactory appearance improvement.

Ectopic thyroid presenting as a gallbladder mass.

The ectopic thyroid tissue is the result of abnormality in embryological development and migration. Ectopic thyroid tissue located in or adjacent to the gallbladder wall is extremely rare with only two cases reported since 1969. These cases were all identified incidentally by pathological examination after cholecystectomy for acute or chronic cholecystitis. We here report a case of ectopic thyroid tissue presenting as a gallbladder mass in a 60-year-old woman who underwent cholecystectomy. Ectopic thyroid tissue in the gallbladder wall was confirmed by histopathology.

[Auricular reconstruction with overlapping tissue expansion techniques].

OBJECTIVE: To investigate a method of auricular reconstruction with overlapping tissue expansion techniques and without skin graft. METHODS: Two tissue expanders were implanted subcutaneously at the mastoid. 6 patients with microtia (overlapping group) were treated. After completion of skin expansion, the expanders were removed. The autologous rib cartilage or Medpor scaffolds were implanted. The flap A made by the upper expanded flap was used to cover the upper part of the front and the back of the framework. The flap B made by lower expanded flap was transplanted to cover the lower part of the back of frameworks. The remaining expanded skin was designed to cover the postauricular wound. The other thirteen microtia patients who treated by the traditional auricular reconstruction were selected as control(traditional group). RESULTS: Skin graft was not necessary in the patients of overlapping groups. The appearance of the reconstructed ear was very satisfactory. Epidermal necrosis of 0.5 cm x 0.5 cm happened at the distal end of postauricular flap in one case. All the other cases had no complication of infection or framework exposure. The patients were followed up for 3-6 months. Compared with the traditional group, the scar in the costal donor site was inconspicuous in overlapping group (P < 0.05). The complication rate was lower and satisfactory rate was higher in overlapping group (P < 0.01 and P < 0.05). But there was hair growth in the helix of reconstructed ear in overlapping group. CONCLUSIONS: The overlapping expansion can provide enough skin for ear reconstruction. The skin graft is not necessary, resulting less donor site scar and low complications.

Littoral cell angioma of the spleen.

Littoral cell angioma (LCA) is a rare primary benign vascular neoplasm of the spleen. The case of a 52-year-old female with LCA is reported. The patient did not have any symptoms or a significant past medical history. Computed tomography (CT) and ultrasound (US) imaging studies showed multiple lesions in the spleen and gallbladder stones. The tumour was removed successfully by laparoscopic splenectomy and simultaneously cholecystectomy was conducted for gallbladder stones. The patient recovered uneventfully. The tumour lining cells were positive for CD31/CD68 markers, and negative for CD34. This is the first report of a LCA combined with gallbladder stones.

Radiofrequency ablation combined with transarterial chemoembolization for unresectable primary liver cancer.

BACKGROUND: Radiofrequency ablation (RFA) followed by transarterial chemoembolization (TACE) for unresectable primary liver cancer (PLC) has not been widely discussed. In this study, the outcome of the combination of RFA with TACE was retrospectively evaluated. METHODS: From May 2003 to March 2008, 127 consecutive PLC patients with a median age of 56.4 +/- 8.8 years underwent RFA plus TACE. All patients were deemed to have unresectable PLC based on their tumor characteristics. The maximal diameter of the tumor was between 1.5 cm and 10.0 cm. Twenty-six cases with small ( 5.0 cm) tumors were included in this study. RFA was performed using a RITA Medical Systems expandable electrode device, which was followed by first-time TACE administration one to two months later. RESULTS: Technical success of RFA was achieved in all 127 patients with no severe treatment-related complications. RFA was performed percutaneously in 16 (13.5%) cases, by laparoscopic approach in 19 (15.7%), and through laparotomy in the remaining 92 (72.4%). RFA response was classified as complete ablation in 48 cases, nearly complete ablation in 28, and partial ablation in 51. The total 1-, 2-, and 3-year survival rates after RFA were 83.1%, 55.7%, and 43.7%, respectively. The survival rates at 3 years were 78.6%, 28.1%, and 0 for complete ablation, nearly complete ablation, or partial ablation groups, respectively. Three-year disease-free survival rates for the complete ablation and nearly complete ablation groups were 50.3% and 21.3%, respectively. RFA response and liver function were significant variables influencing survival time as analyzed using the Cox regression model. CONCLUSION: RFA could be the first-line exterminate treatment for unresectable PLC, and TACE following RFA may assist in eradicating the peripheral viable tissue and micro-metastasis.

[Analysis of the complications following the periareolar reduction mammaplasty using polypropylene mesh as suspension device].

OBJECTIVE: To investigate the cause and the prophylactic measures for the complication following the periareolar reduction mammaplasty using polypropylene mesh as suspension device. METHODS: From Dec. 1999 to Dec. 2005, 78 patients who underwent periareolar reduction mammaplasty using polypropylene mesh as suspension device were analysed. Among them, 47 cases were followed-up for 6 months to 5 years, and their long-term effect was evaluated. RESULTS: Early after operation, complications included seroma (3 cases), infection (3 cases), delayed wound healing (3 cases), and paraesthesia of nipple-areolar complex (1 case). The 47 followed-up patients presented abnormal wave-like skin appearance in superior polar of breast (7 cases), palpable cord-like mammary content in peripheral region of breast (3 cases), widening of periareolar scar and secondary ptosis (2 cases) and paraesthesia of nipple-areolar complex (1 case). All other patients acquired good appearance and felt satisfactory. 2 patients could lactate after operation. 5 patients underwent mammary X-ray radiography after operation. No mesh shadow or calcification was revealed. CONCLUSIONS: Although polypropylene mesh is a good suspension device in reduction mammaplasty, the long-term complication is relatively high because of the hardness of the tissue. More soft tissue is necessary as alternative device for clinical application.

[Surgical treatment of 475 patients with periampullary carcinoma].

OBJECTIVE: To compare of the outcome of all patients who received surgical treatment in one institute for periampullary carcinoma during different intervals over the past 40 years. METHODS: Retrospective review of 475 patients suffering from periampullary carcinoma in intervals 1958 approximately 1976, 1977 approximately 1987, 1988 approximately 1998 and 1999 approximately 2003 is presented. RESULTS: In interval 1958 approximately 1976, for 128 patients, the tumor resection rate was: pancreatic carcinoma (PC) 26.6% (21/79), ampullary carcinoma (AC) 86.2% (25/29), distal bile duct cancer (DBDC) 38.5% (5/13), and duodenal cancer (DC) 57.1% (4/7). In interval 1977 approximately 1987, for 70 patients, the tumor resection rate was: PC 26.7% (16/60), AC 66.7% (4/6), DBDC 100% (1/1), and DC 66.7% (2/3). In interval 1988 approximately 1998, for 147 patients, the tumor resection rate was: PC 20.2% (22/109), AC 75.0% (12/16), DBDC 50.0% (2/4), and DC 66.7% (12/18). In interval 1999 approximately 2003, for 130 patients, the tumor resection rate was: PC 20.4% (20/98), AC 100% (4/4), DBDC 75.0% (12/16), and DB 83.3% (10/12). Cumulatively, from 1958 to 2003, the incidence of DBDC has become significantly higher, and the average of total bilirubin level (TBIL) has gradually been going downward, the average of blood transfusion during operation and the diameter of resected tumor has been becoming smaller. From 1999 to 2003, none of the 130 periampullary carcinoma patients had received biliary drainage before operation. CONCLUSION: Mortality and complication have become significantly lower because of effective improvement in the perioperative preparation and the care after surgery of periampullary cancer in the recent years. Even though the accurate diagnosis has become increasing earlier than before, the resection rate and prognosis of periampullary carcinoma remain poor.

[The expression and interaction of cyclin D1 and p16 in fibroblasts of pathologic scars].

OBJECTIVE: To investigate the expression of cyclin D1, p16, AR and ER in fibroblasts of scars for further understanding the interaction of these factors and the roles that they play in scar development. METHODS: Thirty samples of mature scar, hypertrophic scar and keloid were detected with immunohistochemical method (SP technique) and compared with normal skin. RESULTS: There were on positive results in normal skin and mature scars. The expression of cyclin D1, p16 and AR was higher in hypertrophic scars and keloids than in normal skin with significant difference (P < 0.05). The expression of cyclin D1 in keloids was higher than in hypertrophic scars (P < 0.05). Though the expression of p16 was higher in keloids than in hypertrophic scars, the difference was not significant. There was significant correlation between the expression of cyclin D1 and AR in the pathologic scar. CONCLUSION: The AR played an important role in scar formation and displayed its function through cyclin D1. The expression of p16 could suppress the excessive proliferation of cells to some extent. If the effect was not enough to resist the function of cyclin D1, long-term proliferation of cells would occur and lead to keloid formation. As the expression of cyclin D1 and p16 in hypertrophic scars was in a state of relative equilibrium, the cell proliferation showed a tendency of self-restriction.

Enantioselective total syntheses of slagenins A-C and their antipodes.

Full details of the total syntheses of slagenins A-C (1a-c) and their antipodes (2a-c), novel bromopyrrole alkaloids with a unique tetrahydrofuro[2,3-d]imidazolidin-2-one moiety, are described in which their absolute stereochemistry was established. The key step in the syntheses involves the efficient condensation of dihydrofuran-3-one or glyoxal with urea to construct the slagenin bicycle core.