As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

Objective: To compare the diagnostic performance between panoramic radiography(PR)and cone beam computed tomography(CBCT)in the assessment of external root resorption(ERR)of mandibular second molars associated with impacted third molars. Methods: A total number of 832 patients with 1 074 mesially and horizontally impacted mandibular third molars treated at our institution from January 2019 to December 2020 were retrospectively analyzed. Presence of ERR on the adjacent second molar was investigated with PR and CBCT. Factors affecting the diagnostic accuracy of PR were determined. Results: The overall incidence of ERR in second molars was 33.15%(356/1 074)as detected by CBCT images. The accuracy of PR was 66.39%. Multivariate Logistic regression analyses further revealed that middle and Class Ⅲ impaction, crown contact or overlap with the root of adjacent tooth were risk factors for inaccurate diagnosis of PR(P<0.05). Conclusion The accuracy of detection on ERR of mandibular second molar associated with impacted third molar using panoramic radiography is lower. CBCT is recommended for this clinical scenario.

Objective: To construct a core competency training indicator system for high-level public health talents using the Delphi method, so as to provide insights into optimization of high-level public health talents training. Methods: Based on review of publications pertaining to core competency training for high-level public health talents, in combination with public health priorities and development needs in China, a preliminary indicator system was constructed. Twenty public health experts were invited for two rounds of Delphi expert consultation. Indicators were screened based on the frequency of full marks, mean score and coefficient of variation (CV), and the weight of indicators was determined using the Entropy weight method. The effectiveness of the Delphi expert consultation was evaluated using the active degree, authority coefficient and the consistency degree. Results: Twenty experts participated in the consultation, including 12 men, and there were 6 experts at ages of 30 to 39 years, 8 at ages of 40 to 49 years, and 6 at ages of 50 years and older. There were 17 experts with an educational level of master and above, 19 with senior professional titles and all experts had working experiences for 10 years and longer. The active degrees were 95.24% and 100.00% for two rounds of consultations, and the overall authority coefficient was 0.87. Following two rounds of consultations, all CVs were reduced to below 0.25, and the coordination coefficients were all statistically significant (P<0.05), with a higher coordination coefficient in the second round of consultation than in the first round. The constructed core competency training indicator system for high-level public health talents included four primary indicators, including health protection, health service improvement, health promotion, and essential quality, with weights of 0.388, 0.310, 0.122 and 0.180, 11 secondary indicators, with high weights seen for protection of human health from threats (0.178), monitoring and assessment of health service utilization (0.157) and promotion of health service quality and access (0.112), and 70 tertiary indicators, with high weights seen for Chinese writing (0.038), capability for health policy suggestions (0.034) and global perspective (0.030). Conclusion The core competency training indicator system for high-level public health talents constructed in this study may provide insights into training of high-level public health talents.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, and most patients with HCC are diagnosed at an advanced stage. Before 2017, tyrosine kinase inhibitors were the main drugs for the treatment of advanced hepatocellular carcinoma. With the emergence of immune checkpoint inhibitors (ICIs), immunotherapy has gradually brought new hope to such patients. At present, the combination of ICIs and other systemic or local treatments has become a potential strategy for the treatment of advanced hepatocellular carcinoma, and some of these combinations have been included in large-scale clinical trials. The main challenges of immunotherapy for advanced hepatocellular carcinoma include the exploration of predictive biomarkers, management of immune-related adverse events, and exploration of effective combination regimens. This article provides the latest research progress on the single or combined use of ICIs and other immunotherapy for hepatocellular carcinoma and discusses the limitations of current research and clinical application and the future development direction.

Soft tissue sarcoma (STS) is a highly heterogeneous group of malignant tumors originating from mesenchymal tissues. The most common sites of STS are limbs (45%), viscera (21%) and retroperitoneum (17%). The incidence of head and neck soft tissue sarcomas (HNSTS) is the lowest (5%) compared with other areas of the body. Due to numerous functional organs and delicate and complex anatomical structures of the head and neck, it is often difficult to perform radical surgical treatment. Therefore, radiotherapy plays an important role in the treatment of HNSTS. Due to its low incidence, radiotherapy for HNSTS has been rarely studied and captivated little attention. In this article, the present situation and clinical evidence of radiotherapy for HNSTS were summarized, aiming to provide reference for clinical practice.

Objective:To compare 5-year overall survival (OS) and disease free survival (DFS) between preoperative three dimensional conformal radiotherapy (3DCRT) and volumetric medulated arc therapy (VMAT) concurrently combined with chemotherapy for locally advanced rectum cancer (LARC), and analyze the value of induction and/or consolidation chemotherapy in these circumstances.Methods:334 patients with LARC treated with preoperative 3DCRT (172 cases) and VMAT (162 cases) concurrently combined with chemotherapy, main protocol XELOX (capecitabine plus oxaplatin), and subsequent surgery in Sun Yat-sen University from May 2007 to April 2013 were retrospectively analyzed. The radiation prescription dose for VMAT group was 50 Gy 25 fractions for planning target volume1(PTV 1), and 46 Gy 25 fractions for PTV 2. The radiation prescription dose for 3DCRT group was 46 Gy 23 fractions for PTV 2. One hundred and eighty-five cases of all received preoperative concurrent chemoradiotherapy (namely, CCRT group), 149 cases received preoperative concurrent chemoradiotherapy plus median 2 courses (1-7 courses) induction and/or consolidation chemotherapy (namely, CCRT±induction chemotherapy±consolidation chemotherapy group), whose main chemotherapy protocol was XELOX. Difference of 5-year OS and DFS between 3DCRT and VMAT group was compared. The rate differences of acute toxicity during chemoradiotherapy, postoperative complications, ypCR, and survival between CCRT group and CCRT±induction chemotherapy±consolidation chemotherapy group were analyzed. Results:After a median follow-up of 62.3 months (2.4-119months) for the 334 patients, no any significant difference for 5-year OS (79.0% vs. 83.2%, P=0.442) and 5-year DFS (77.0% vs. 82.1%, P=0.231) between 3DCRT and VMAT group was observed. There was no any significant difference for the Grade 3 hematological toxicity (7.0% vs. 12.1%, P=0.114) and non-hematological toxicity (14.1% vs. 16.8%, P=0.491) during chemoradiotherapy, postoperative complications (17.3% vs. 17.4%, P=0.971), ypCR rate (25.4% vs. 30.2%, P=0.329), 5-year OS (80.5% vs. 82.0%, P=0.714) and 5-year DFS (78.8% vs. 81%, P=0.479) between CCRT group and CCRT±induction chemotherapy±consolidation chemotherapy group. Conclusions:Compared with 3DCRT, the physics advantage of VMAT technique does not significantly convert into clinical benefits and improve 5-year OS and DFS, even further boosting radiation dose to the gross tumor volume. It is safe for median 2 courses of induction and/or consolidation chemotherapy before and or after preoperative concurrent chemoradiotherapy in the treatment of LARC, though it does not significantly improve ypCR rate and survival.

Bacitracin is a broad-spectrum cyclic peptide antibiotic, and mainly produced by Bacillus. Energy metabolism plays as a critical role in high-level production of target metabolites. In this study, Bacillus licheniformis DW2, an industrial strain for bacitracin production, was served as the original strain. First, our results confirmed that elimination of cytochrome bd oxidase branch via deleting gene cydB benefited bacitracin synthesis. Bacitracin titer and ATP content were increased by 10.97% and 22.96%, compared with those of original strain, respectively. Then, strengthening cytochrome aa3 oxidase branch via overexpressing gene qoxA was conducive to bacitracin production. Bacitracin titer and ATP content were increased by 18.97% and 34.00%, respectively. In addition, strengthening ADP synthesis supply is also proven as an effective strategy to promote intracellular ATP accumulation, overexpression of adenosine kinase DcK and adenylate kinase AdK could all improve bacitracin titers, among which, dck overexpression strain showed the better performance, and bacitracin titer was increased by 16.78%. Based on the above individual methods, a method of combining the deletion of gene cydB and overexpression of genes qoxA, dck were used to enhance ATP content of cells to 39.54 nmol/L, increased by 49.32% compared to original strain, and bacitracin titer produced by the final strain DW2-CQD (DW2ΔcydB::qoxA::dck) was 954.25 U/mL, increased by 21.66%. The bacitracin titer produced per cell was 2.11 U/CFU, increased by 11.05%. Collectively, this study demonstrates that improving ATP content was an efficient strategy to improve bacitracin production, and a promising strain B. licheniformis DW2-CQD was attained for industrial production of bacitracin.
Bacillus licheniformis ; metabolism ; Bacitracin ; biosynthesis ; Energy Metabolism ; genetics ; Industrial Microbiology ; methods

Objective:To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT).Methods:A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method.Results:In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% ( P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups ( P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant ( P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group ( P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group ( P<0.001). Conclusions:W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.

Objective:To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT).Methods:A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method.Results:In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% ( P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups ( P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant ( P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group ( P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group ( P<0.001). Conclusions:W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.

Objective To investigate the feasibility of non-operative management (NOM) by comparing the therapeutic effects between NOM and total mesorectal excision (TME) for rectal cancer patients with clinical complete response (cCR) after neo-adjuvant chemoradiotherapy.Methods A total of 135 patients with stage Ⅱ/Ⅲ rectal cancer who obtained cCR after neo-adjuvant chemoradiotherapy in Sun Yat-sen University Cancer Center from 2006 to 2016 were recruited and assigned into the NOM (n =43) and standard operative management (SOM) groups (n=92).The local recurrence rate,accumulative local control (LC) rate after salvage therapy,disease-free survival (DFS),overall survival (OS) and sphincter preservation rate were statistically compared between two groups.Kaplan-Meier analysis and log-rank test were utilized to calculate the LC,OS and DFS.Chi-square test was performed to calculate the sphincter preservation rate.Results The mean follow-up duration was 39 months (range:10-127 months).Of 135 patients,the local recurrence rate and distant metastasis rate were 3.7％ and 11.1％,and the 3-year DFS and OS were 90.5％ and 97.0％.In the NOM and SOM groups,the 3-year DFS were 87％ and 93％,and the 5-year DFS were 73％ and 87％(P=0.089).The 3-year OS were 98％ and 99％,and the 5-year OS were 98％ and 97％ (P=0.578).In the NOM group,the local recurrence rate was 12％ (n =5),80％ of patients received salvage treatment and the accumulative LC rate was calculated as 98％.In the SOM group,the local recurrence rate was 0,which was significantly lower than that in the NOM group (P=0.O10).In the NOM group,the sphincter preservation rate was 93％,significantly higher compared with 70％ in the SOM group (P=0.030).Conclusions It is feasible for rectal cancer patients with cCR to receive NOM following neo-adjuvant chemoradiotherapy.Partial locally recurrent patients can be healed by timely salvage therapy,thereby averting TME and relevant complications and enhancing the quality of life of rectal cancer patients.