[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

The effect of microRNA-663b in the inhibition of interleukin-1-induced nucleus pulposus cell apoptosis and inflammatory response.

The aim of this study was to explore the role and pathological mechanism of microRNA-663b in interleukin-1beta (IL-1ß)-induced inflammation and apoptosis of nucleus pulposus cells. First, the best concentration and time to construct the nucleus pulposus cell inflammation model was screen out. Overexpression or inhibition of miR-663b expression was performed by adding microRNA-663b mimic or microRNA-663b inhibitor. 293T cells were transfected according to experimental requirements. The luciferase activity of each group was detected to analyze the targeted regulation of microRNA-663b on interleukin-1 receptor (IL1R1). Compared with the mimic negative control (NC) group, the expression of inflammatory factors in the microRNA-663b overexpression group was inhibited (P<0.05), and the expression of type 2 collagen and polysaccharide protein increased (P<0.05), and the apoptosis of nucleus pulposus cells was inhibited (P<0.01), and the number of TUNEL-positive cells decreased significantly (P<0.01), and the microRNA and protein expression of IL1R1, the ratio of P-P65/P65 and phospho-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (P-IκBα)/nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) protein expression were significantly decreased (P<0.05). The expression of inflammatory factors in the miR-663b inhibitor group was significantly higher than that in the inhibitor NC group (P<0.01), and the expression of type 2 collagen and polysaccharide protein was significantly decreased (P<0.01), and the number of apoptosis cells and TUNEL staining positive cells increased (p<0.01). The expression of IL1R1 gene and protein was significantly increased (P<0.01). The ratio of P-P65/P65 and P-IκBα/IκBα protein expression increased (P<0.05). IL1R1 is a downstream target gene of microRNA-663b. MicroRNA-663b may down-regulate the expression of IL1R1 at the transcriptional level by targeting IL1R1, inhibit the inflammatory response of nucleus pulposus cells, and slow down the degeneration of nucleus pulposus cells.

[Correlation between pelvic relapses of rectal cancer after radical and R0 resection: A regression model-based analysis].

Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.

[Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy].

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Correlation analysis between lactic, procalcitonin and disease severity in patients with imported malaria from Africa].

Objective: To explore the clinical characteristics, the correlation between lactate, procalcitonin and disease severity of imported malaria from Africa. Methods: The clinical data of 186 patients with imported malaria were collected from January 1, 2018 to April 30, 2021 in the Guangzhou Eighth People's Hospital, Guangzhou Medical University. The general conditions, clinical symptoms, laboratory tests, treatment, and prognosis of the patients were analyzed retrospectively. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of relevant indicators in predicting severe malaria. Results: A total of 186 patients were divided into severe cases (n=48) and non-severe cases (n=138) in this study, of which the mean age was (38.3±10.3) years, 169(90.9%) cases were male, 17(9.1%) cases were female. The main infection species was Plasmodium falciparum, in a total of 166 cases (89.2%). The severe cases were all falciparum malarias. Compared with the non-severe group, the lactic, procalcitonin, white blood cell count and neutrophil count of the severe group were all increased, the differences were all statistically significant (all P<0.01); the percentage of monocytes, red blood cell count, hemoglobin, hematocrit and platelet count were all decreased, the difference were all statistically significant (all P<0.01). The areas under the ROC curves (AUC)(95%CI) of lactate, procalcitonin, red blood cell count, hemoglobin, hematocrit and platelet count for predicting severe malaria was 0.753(0.663-0.844), 0.755(0.670-0.841), 0.782(0.700-0.864), 0.738(0.652-0.823), 0.760(0.676-0.844), 0.778(0.699-0.857), respectively (all P<0.01). When the Youden indexes were at their maximum, the best cut-off value of lactic was 2.29 mmol/L, with sensitivity in predicting of severe malaria was 56.3%, and the specificity was 93.5%; the best cut-off value of procalcitonin was 2.12 µg/L, with sensitivity in predicting of severe malaria was 77.1%, and the specificity was 68.1%. The fatality rate of severe malaria was 4.2% (2/48). Conclusions: Anemia and thrombocytopenia are common indicators for predicting the severity of malaria. Lactic and procalcitonin also have higher predictive value for severe malaria, which could help to identify severe malaria as early as possible, improve the cure rate and reduce the risk of death.

Lung cancer screening study from a smoking population in Kunming.

OBJECTIVE: Yunnan, China, is a central tobacco-producing region with a large smoking population and an increasing incidence of lung cancer in recent years. This study aimed to understand the incidence of lung cancer and the characteristics of lung nodules on low-dose computed tomography (LDCT) scans of the chest in a long-term smoking population in Kunming. PATIENTS AND METHODS: Long-term smokers in Kunming who were not at risk of evident lung disease symptoms were recruited through recommendation and publicity by the Kunming University of Science and Technology. RESULTS: Among 375 cases eligible for inclusion,14 cases of lung cancer were detected with a detection rate of 3.73% (95% CI: 2.55%-4.27%), including one case of squamous carcinoma, one case of small cell lung cancer, seven cases of adenocarcinoma of the lung and five cases of early-stage lung cancer (35.71%). In the group of < 6 mm solid nodules and < 5 mm non-solid nodules, no lung cancer was detected in 201 cases; lung cancer was detected in 14 cases in 61 cases, and there was a statistical difference between the two groups (p < 0.05). CONCLUSIONS: The lung cancer detection rate in long-term smokers was high, with the type predominantly adenocarcinoma and a high incidence of lung nodules, and increased when solid nodules≥6 mm or non-solid nodules ≥ 5 mm were present. It is recommended that screening for lung cancer by LDCT of the chest be introduced in the male smoking population who meet the risk factors and that screening for lung cancer in women should be redefined as a high-risk factor.

[Cone-beam CT analysis of the correlation between incisor root resorption rate and tooth movement index in adult patients with fixed orthodontics appliance].

Objective: To analyze the correlation between the root resorption rate and tooth movement of the maxillary and mandibular incisors before and after orthodontic treatment in adult patients using cone-beam CT (CBCT), and to explore the related factors that affect the apical root resorption. Methods: In this retrospective study, 23 adult patients with classⅠor class Ⅱ division 1 malocclusion [2 males and 21 females, mean age (23.4±6.3) years, treatment time (2.1±0.7) years] who received orthodontic treatment with fixed appliance in Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital from January 2017 to June 2021 were enrolled. Full-column CBCT examination was performed before and after treatment. A three-dimensional model was established to observe and record the volume of the maxillary and mandibular central and lateral incisors before and after treatment. The change of the incisal edge, the angle of rotation of the incisal edge, and the direction of the long axis of the tooth were also measured. The root resorption in each tooth before and after treatment was compared, and the root resorption rate was calculated. Pearson correlation analysis was performed on the root absorption rate before and after treatment with age, treatment time and tooth movement. Results: After treatment, the tooth volume of the maxillary and mandibular central and lateral incisors decreased significantly (P<0.01). The root absorption volumes were (20.2±6.0) mm3 and (11.2±4.7) mm3 in maxillary central and lateral incisors, and (14.7±4.6) mm3 and (14.8±5.0) mm3 in mandibular central and lateral incisors, respectively. The root absorption rates were (9.49±1.75)% and (9.13±3.24)% in maxillary central and lateral incisors, and (8.56±3.43)% and (9.13±3.24)%, in mandibular central and lateral incisors, respectively (F=0.56, P=0.640). The root resorption rate of maxillary central incisors had a weak positive correlation with the change of sagittal distance of incisal edge (r=0.36, P=0.015). The root resorption rate of mandibular central incisors had a moderate positive correlation with the vertical movement distance (r=0.48, P=0.001). The root resorption rate of mandibular lateral incisors was weakly positively correlated with the vertical movement of incisal edge and the treatment time (r=0.35, P=0.016; r=0.34, P=0.021), and was moderately positively correlated wit the change of sagittal movement of incisal edge (r=0.44, P=0.002). Conclusions: During orthodontic treatment, both maxillary and mandibular incisors had a certain degree of root resorption, which was related to sagittal and vertical movement of the incisors and the time of orthodontic treatment.

Finger touching combined X-ray-guided percutaneous nephrolithotomy in 640 cases: an 8-years' experience.

OBJECTIVE: We aimed to evaluate the safety and efficacy of finger touching combined X-ray-guided percutaneous nephrolithotomy, and the feasibility of avoiding damage in medical staff caused by X-ray. PATIENTS AND METHODS: From January 2013 to December 2020, 640 cases of percutaneous nephrolithotomy were performed through the 18-24-F channel. Among those cases, 22 (3.4%) cases were double-sided kidney stones surgeries, 294 (45.8%) cases were on the right side and 324 (50.5%) cases were on the left side. The targeted renal calyceal puncture was carried out under the combined guidance of the doctor's finger and X-ray. We assessed the X-ray exposure time of patients and doctors, average number of punctures, postoperative hospitalization, calculus removal rates, and complications. RESULTS: The average number of punctures was 2.8 ± 1.4. Average X-ray exposure time during procedure: 2.8 s (range: 2-8 s). Average surgical time: 106.5 ± 49.4 min. Postoperative hospitalization: 6.8 ± 4.2 d. Average reduced hemoglobin level: 5.9 g/day. Stone-free rate 4 weeks after surgeries: 95.6%. Patients with upper ureteral calculi: 395 cases (61.72%). The calculus residual rate of patients with staghorn renal calculi or multiple renal calculi complementary treatments was 82.9%, including 0 patients who received shock wave lithotripsy, 2 cases of repeated percutaneous nephrolithotomy (PCNL), and 18 cases of ureteroscopy. Postoperative placement of renal drainage tube occurred in 52 cases. As for complications, no perirenal infection occurred, two severe bleeding complication cases occurred, and one case of colon perforation occurred. CONCLUSIONS: Finger touching combined X-ray-guided percutaneous nephrolithotomy in patients with renal calculus is safe and can accurately guide the puncture without radiation hazards. The placement of a renal drainage tube was beneficial to reduce renal effusion, hematocele, and infections.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

[A new classification of maxillary defect and simultaneous accurate reconstruction].

Objective: To select the preferred flaps for the reconstruction of different maxillary defects and to propose a new classification of maxillary defects. Methods: A total of 219 patients (136 males and 83 females) underwent the simultaneous reconstruction of maxillary defects in the Beijing Tongren Hospital, Capital Medical University, between January 2005 and December 2018 were reviewed. Age ranged from 16 to 78 years. Based on the proposed new classification of the maxillary defects, 22 patients with class Ⅰ defects (inferior maxillectomy), 44 patients with class Ⅱ defects (supperior maxillectomy), 132 patients with class Ⅲ defects (total maxillectomy) and 21 patients with class Ⅳ defects (extensive maxillectomy) were enrolled. Survival rate, functional and aesthetic outcomes of flaps were evaluated. Survival analysis was performed in 169 patients with malignant tumor, Kaplan-Meier method was used to calculate the survival rate, and Log-rank method was used to compare the difference of survival rate in each group. Results: A total of 234 repairs for maxillary defects were performed in 219 patients. Fibula flaps were used in 4/13 of class Ⅰ defects; temporal muscle flaps (11/24, 45.8%) and anterolateral thigh flaps (6/24, 25.0%) used in class Ⅱ defects; temporal muscle flaps (71/128, 55.5%), anterolateral thigh flaps (6/24, 25.0%) and fibula flaps (12/128, 9.4%) used in class Ⅲ defects; and anterolateral thigh flaps (8/20, 40.0%) and rectus abdominis flaps (8/20, 40.0%) used in class Ⅳ defects. The success rate of local pedicled flaps was 95.6% (109/114) and that of free flaps was 95.8% (115/120). Thrombosis(10/234,4.3%) was a main reason for repair failure. Among the followed-up 88 patients, swallowing and speech functions recovered, 82 (93.2%) of them were satisfied with appearance, and 75 (85.2%) were satisfied with visual field. The 3-year and 5-year overall survival rates were 66.5% and 63.6%, and the 3-year and 5-year disease-free survival rates were 57.1% and 46.2%, respectively, in the 169 patients with malignant tumors. Conclusion: A new classification of maxillary defects is proposed, on which suitable flaps are selected to offer patients good functional and aesthetic outcomes and high quality of life.

[The expression of clock gene CLOCK and its clinical significance in nasopharyngeal carcinoma].

Objective: To explore the relationship between expression levels of CLOCK mRNA and protein and the clinical characteristics of patients with nasopharyngeal carcinoma. Methods: The frozen tissue specimens from 33 patients with nasopharyngeal carcinoma in the Affiliated Tumor Hospital of Guizhou Medical University from 2018 to 2019 were collected. Seventeen cases of tissue specimens from patients with nasopharyngeal chronic inflammation in the Affiliated Hospital of Guizhou Medical University in 2019 were collected. From 2008 to 2014, 68 cases of formalin-fixed paraffin-embedding (FFPE) nasopharyngeal carcinoma tissue and 37 cases of FFPE nasopharyngeal chronic inflammation tissue were collected from the Affiliated Tumor Hospital of Guizhou Medical University. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to detect the mRNA and protein expression levels of CLOCK. The nasopharyngeal carcinoma cells including CNE1, CNE2, 5-8F and the normal nasopharyngeal epithelial cell NP69 were cultured. qRT-PCR was used to detect the expression level of CLOCK mRNA in each cell line at the time points of ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22. The cosine method was used to fit the rhythm of CLOCK gene in nasopharyngeal carcinoma. The protein expression of CLOCK protein was detected by using immunohistochemical method in 68 cases of nasopharyngeal carcinoma and 37 cases of nasopharyngeal chronic inflammation tissue. Survival was analyzed by Kaplan-Meier method and Log rank test, and the influencing factors was analyzed by Cox regression model. Results: The expression levels of CLOCK mRNA in CNE1, CNE2 and 5-8F cells (0.63±0.07, 0.91±0.02 and 0.33±0.04, respectively) were lower than that in NP69 cell (1.00±0.00, P<0.05). The expression levels of CLOCK protein in CNE1, CNE2 and 5-8F cells (0.79±0.06, 0.57±0.05 and 0.74±0.10, respectively) were lower than that of NP69 cells (1.00±0.00, P<0.05). The expressions of CLOCK mRNA in nasopharyngeal carcinoma cells including CEN1, CNE2, 5-8F and normal nasopharyngeal epithelial cell NP69 were different at different time points, with temporal fluctuations. The fluctuation periods of CLOCK mRNA in CNE1, CNE2, 5-8F, and NP69 cells were 16, 14, 22 and 24 hours, respectively. The peak and trough times were ZT10: 40 and ZT18: 40, ZT10 and ZT3, ZT14: 30 and ZT3: 30, ZT12: 39 and ZT0: 39, respectively. CLOCK mRNA and protein expression levels in nasopharyngeal carcinoma tissues (0.37±0.20 and 0.20±0.26, respectively) were lower than those in nasopharyngeal chronic inflammation tissues (1.00±0.00 and 0.51±0.41, respectively, P<0.05). The 1, 3, and 5-year survival rates of patients in the CLOCK protein high expression group (CLOCK protein expression level ≥ 0.178) were 96.2%, 92.1%, and 80.1%, respectively, which were higher than those in the low expression group (CLOCK protein expression level <0.178, 92.9% , 78.6% and 57.1%, respectively, P=0.009). The 1, 3, and 5-year progression-free survival (PFS) rates of patients in the CLOCK protein high expression group were 96.2%, 87.8%, and 87.7%, respectively, which were higher than those in the low expression group (92.7%, 82.2%, and 70.8%, respectively, P=0.105). Compared with the low-expression group (100.0%, 96.9%, and 90.0%, respectively), the 1, 3, and 5-year recurrence-free survival rates of patients in the CLOCK protein high expression group (100.0%, 95.7%, and 95.7%, respectively) were not statistically significant (P=0.514). Compared with the low-expression group (92.7%, 82.2%, and 79.3%), the 1, 3, and 5-year survival rates without metastasis in the CLOCK protein high expression group (96.2%, 92.0%, and 92.0%, respectively) were not statistically significant (P=0.136). CLOCK protein expression and T stage were independent prognostic factors of overall survival (P<0.05). Conclusions: The expression of CLCOK is downregulated in the nasopharyngeal carcinoma cell and nasopharyngeal carcinoma tissues. Clock gene CLOCK is rhythmically expressed in the nasopharyngeal carcinoma cells and normal nasopharyngeal epithelial cells. Compared with normal nasopharyngeal epithelial cells, the fluctuation period of CLOCK in nasopharyngeal carcinoma cells is shortened. The overall survival of patients in the CLOCK protein high expression group is better than that of low expression group. The expression of CLOCK protein is an independent influencing factor for overall survival. CLOCK gene may be a potential tumor suppressor gene in the nasopharyngeal carcinoma.

[The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma (nasal type) and its individualized application].

Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage Ⅰ/Ⅱ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage Ⅰ/Ⅱ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.

[Safety analysis of definitive surgery for chronic radiation intestinal injury].

Objective: To investigate the safety of definitive surgery for chronic radiation intestinal injury. Methods: A descriptive case series study was performed. Clinical data of 105 patients who were diagnosed as chronic radiation intestinal injury, had complete data and received definitive surgery (the radiation-induced intestinal segment and digestive tract reconstruction) at Department of Gastrointestinal Surgery of Beijing Tsinghua Changgung Hospital from June 2016 to May 2020 were retrospectively analyzed. There were 30 males (28.6%) and 75 females (71.4%) with the median age of 58 years (P25, P75: 52, 64 years). Patients who had tumor recurrence or refused surgical treatment were excluded. According to the preoperative evaluation and clinical manifestations, to select the resection range. Outcome parameters: (1) preoperative evaluation (nutrition risk assessment and status of obstruction or fistula); (2) clinical manifestations and treatment strategies; (3) details of surgical parameters; (4) postoperative complications, and Clavien-Dindo classification III to V was defined as main moderate-severe complication. Results: (1) Preoperative evaluation: Eighty-eight patients (83.8%) developed symptoms of chronic radiation intestinal injury more than 1 year after the end of radiotherapy. Ninety-eight patients (93.3%) had preoperative NRS-2002 score ≥3, 74 patients (70.5%) received preoperative parenteral nutritional support, and the median time of nutritional support was 10.5 (7.0, 16.0) days. Sixteen patients (15.2%) received small intestinal decompression tube implantation due to severe obstruction. (2) Clinical manifestations and treatment strategies: Among 105 patients, 87 (82.9%) presented with obstruction and received definitive resection of the radiation-induced intestinal segment plus one-stage digestive tract reconstruction; 18 (17.1%) presented with intestinal fistula and all of them received definitive resection of the radiation-induced intestinal segment, intestinal fistula plus one-stage digestive tract reconstruction. Among above 18 patients with fistula, 3 patients with ileorectal stump fistula received pedicled pelvic closure of greater omentum at the same time; 4 patients had ileal vesical fistula, of whom 2 patients received cystectomy and bladder repair due to preoperative nephrostomy decompression, and the other 2 patients received transection of the small intestine proximal and distal to the fistula and anastomosis of the intestinal loop without fistula resection, intestinal fistula or bladder fistula repair. (3) The details of surgical parameters: Median operative time and intraoperative blood loss was 230 (180, 300) minutes and 50 (20, 50) ml respectively. Ninety-two patients (92/105, 87.6%) underwent ileocolonic anastomosis, and anastomosis on the hepatic flexure or splenic flexure colon were performed in 88 (83.8%) and 4 (3.8%) patients respectively. Ileoileal anastomosis was performed in 13 patients (12.4%). The anastomotic site of 92 patients (87.6%) was strictly located in the contralateral quadrant of the radiation field, and the anastomotic site of 13 patients (12.4%) was far from the radiation field. Nine patients (8.6%) had more than one anastomosis, 5 patients (4.8%) had less than 180 cm of residual small intestine, 7 patients (6.7%) underwent retrograde intestinal permutation, 4 patients (3.8%) underwent abdominal wall reconstruction surgery due to abdominal wall defects, and 87 patients (82.9%) had severe abdominal pelvic adhesions (grade 3-4 adhesions). Intraoperative complications occurred in 3 patients (2.9%), which were found in time and handled properly. The median postoperative hospital stay was 13.0 (12.0, 24.5) days, and all the patients had resumed oral feeding upon discharge. (4) Postoperative complications: Fourteen patients (13.3%) had 18 major complications (grade III to V). The incidence of postoperative anastomotic leakage was 5.7% (6/105), and the incidence of anastomotic leakage for ileocolon anastomosis and ileoileal anastomosis was 2.2% (2/92) and 4/13, respectively (χ(2)=17.29, P<0.001). The incidence of postoperative anastomotic leakage of intestinal fistula and intestinal obstruction was 3/18 and 3.4% (3/87), respectively (χ(2)=4.84, P=0.028). The mortality at 30 days after operation was 1.0% (1/105), after abdominal infection and septic shock caused by postoperative anastomotic leakage resulting in multiple organ failure. Conclusion: For chronic radiation intestinal injury patients with obstruction or fistula, definitive surgical treatment is feasible and safe with acceptable major complications.

[Screening and analysis of Treponema pallidum specific antibody among childbearing age people in rural areas of Yunnan province, 2013-2017].

Objective: To determine the prevalence, epidemiological characteristics, and related factors of syphilis infection among rural childbearing age people to promote medical interventions on pre-pregnancy aristogenesis and syphilis infection in Yunnan province. Methods: The subjects in this study were 18-49-year-old rural couples of childbearing age from the National Free Preconception Health Examination Project in Yunnan province during 2013-2017. The descriptive study was carried out to determine the positive rate of Treponema pallidum specific antibody (TPsAb) and related sociodemographic characteristics. Results: The overall positive rate of TPsAb was 0.38% (8 204/2 160 455) in 2 160 455 rural childbearing age people in Yunnan. The positive rate of TPsAb was 0.39% (4 019/1 040 981) in men,higher than that in women (0.37%,4 185/1 119 474). The positive rate of TPsAb was highest in the age group 45-49 years (0.70%,158/22 511). The positive rate of TP antibody in the minority ethnic groups and Han ethnic groups appeared the same (0.38%). However,the highest positive rate of TPsAb was 0.77% (461/60 153) in Hani ethnic group among all the 17 minority ethnic groups. People with education level of primary education had the highest anti-TP positive rate (0.54%,2 327/431 275). The positive rate of TPsAb appeared the highest in Zhaotong (0.73%, 2 049/281 614) area among all the 16 prefectures of the province. The positive rate of TPsAb in the population from the impoverished regions (0.50%,2 963/590 039) was higher than in other disadvantaged areas (0.34%, 3 115/929 368) or areas with average income (0.33%,2 126/641 048). Significant differences appeared in the positive rate of TPsAb among populations of different ages, ethnic, education level, and economic level groups (trend χ2 test, P<0.001). Conclusions: The positive rate of TP antibody in rural childbearing age people in Yunnan was related to multi factors,including sex,age,ethnic group,education level,area, residence, and local economic situation. The positive rate of TPsAb was higher in men than in women. And people with elder age, lower education level, being Hani or Lahu ethnic group, and Zhaotong areas had higher TPsAb positive rates and higher syphilis infection risk.

[Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy].

Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval (HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment (HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status (HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval (HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment (HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence (HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status (HR=1.69, 95% CI: 1.02-2.81), the recurrence interval (HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence (HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

[Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type].

Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

[Comparison of preoperative chemotherapy with concurrent chemoradiotherapy combined with TME for 305 patients with locally advanced rectal cancer].

Objective: To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer. Methods: Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM). Results: In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant (P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively (P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% (P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% (P>0.05), local recurring free survival rates were 100% and 92.3% (P>0.05), distant metastasis free survival rate were 75.6% and 77.3% (P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival (P<0.05). Conclusion: In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

[Study on the prognostic value of preoperative anti hepatitis B virus therapy in patients with hepatocellular carcinoma complicated with microvascular tumor thrombus and establishment of survival prediction model].

Objective: To explored the effect of preoperative antiviral therapy on the prognosis of microvascular tumor thrombi patients, and to established a prognostic prediction model for these patients after radical resection of liver cancer. Methods: The clinicopathological and survival data of hepatocellular carcinoma patients with microvascular tumor thrombus who underwent radical resection in the Third Affiliated Hospital of Sun Yat-sen University from January 1, 2013 to December 31, 2015 were retrospectively collected. Kaplan-Meier method was used to calculate the survival curve, and log-rank test was used to compare the prognosis of patients with and without antiviral treatment before operation. Univariate and multivariate Cox proportional hazard regression model was used to screen predictive factors. R software was used to make predictive nomogram, and discrimination and calibration degree were used to evaluate the prediction model. Results: Among all 153 patients, 22 were female and 131 were male, aged (51.3±11.7) years. The preoperative antiviral therapy significantly improved overall survival and recurrence-free survival (χ2=41.423, 54.389; both P<0.001). According to the results of multivariate and regression analysis, preoperative antiviral therapy (HR=0.301,95%CI:0.171-0.532,P<0.001), alpha fetoprotein (HR=1.226,95%CI:1.157-1.776,P=0.032) and tumor size (HR=1.008,95%CI:1.001-1.016,P=0.02) were important prognostic factors for overall survival. The area under curve value of 3-year survival prediction model was 0.749(95%CI: 0.712-0.782), and that of 5-year survival prediction model was 0.755(95%CI: 0.724-0.793), with good calibration. Conclusions: Preoperative anti hepatitis B virus(HBV) therapy can significantly improve the prognosis of patients with hepatocellular carcinoma complicated with microvascular tumor thrombus, we develope the prediction models of 3-year and 5-year survival rate that can improve the reference for clinical work and benefit patients.