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:This study aimed to assess the infection status of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in healthy populations in China over the past decade and analyze the differences in CMV and EBV infection and related risk factors in healthy populations before and after the lifting of coronavirus disease 2019 (COVID-19) pandemic control measures.Methods:This study retrospectively analyzes the CMV and EBV infection status of 8 827 healthy donors who underwent prehematopoietic stem cell transplantation screening at Peking University People's Hospital from January 2014 to December 2023. Logistic regression analysis was conducted to determine the risk factors for CMV and EBV infection.Results:The CMV and EBV IgG positivity rates were 94.52% and 95.40% among the healthy donors, respectively, with no significant differences before and after the lifting of pandemic control measures (all P value>0.05). However, IgG antibody titers increased [CMV: (100.44±36.50) U/ml vs (109.98±36.31) U/ml, P<0.001; EBV: (281.57±226.79) U/ml vs (361.08±268.58) U/ml, P<0.001] after lifting the COVID-19 restrictions. However, the CMV IgM positivity rate remained unchanged. The EBV IgM positivity rate significantly increased after lifting measures (2.77% vs 6.29%, P<0.001), reaching 8.10% within 3 months. Further analysis of the factors affecting EBV IgM positivity revealed that gender ( OR=1.479, 95% CI 1.169-1.872, P=0.001), age[compared with the group younger than 18 years, the 18-50-year age group ( OR=0.584, 95% CI 0.421-0.820, P=0.002), the >50-year age group ( OR=0.389, 95% CI 0.248-0.610, P<0.001) ], and the lifting of COVID-19 restrictions ( OR=2.360, 95% CI 1.287-3.047, P<0.001) were independent factors influencing EBV IgM positivity in the general population. The EBV IgM positivity rate in individuals under 18 years old was not affected by gender or the lifting of COVID-19 restrictions when stratified by age group. Both genders ( OR=1.499, 95% CI 1.138 - 1.975, P=0.004) and the lifting of COVID-19 restrictions ( OR=2.608, 95% CI 1.940-3.507, P<0.001) were independent factors affecting EBV IgM positivity in the 18-50-year age group. The lifting of COVID-19 restrictions ( OR=2.222, 95% CI 1.101-4.484, P=0.026) was the sole independent factor affecting EBV IgM positivity in individuals over 50 years old. Conclusions:Previous infection rates of CMV and EBV are high in healthy populations in China, which increase with age. COVID-19 infection may increase EBV reactivation rates in healthy individuals, with a more pronounced effect on those aged >18 years.

Objective:This study aimed to assess the infection status of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in healthy populations in China over the past decade and analyze the differences in CMV and EBV infection and related risk factors in healthy populations before and after the lifting of coronavirus disease 2019 (COVID-19) pandemic control measures.Methods:This study retrospectively analyzes the CMV and EBV infection status of 8 827 healthy donors who underwent prehematopoietic stem cell transplantation screening at Peking University People's Hospital from January 2014 to December 2023. Logistic regression analysis was conducted to determine the risk factors for CMV and EBV infection.Results:The CMV and EBV IgG positivity rates were 94.52% and 95.40% among the healthy donors, respectively, with no significant differences before and after the lifting of pandemic control measures (all P value>0.05). However, IgG antibody titers increased [CMV: (100.44±36.50) U/ml vs (109.98±36.31) U/ml, P<0.001; EBV: (281.57±226.79) U/ml vs (361.08±268.58) U/ml, P<0.001] after lifting the COVID-19 restrictions. However, the CMV IgM positivity rate remained unchanged. The EBV IgM positivity rate significantly increased after lifting measures (2.77% vs 6.29%, P<0.001), reaching 8.10% within 3 months. Further analysis of the factors affecting EBV IgM positivity revealed that gender ( OR=1.479, 95% CI 1.169-1.872, P=0.001), age[compared with the group younger than 18 years, the 18-50-year age group ( OR=0.584, 95% CI 0.421-0.820, P=0.002), the >50-year age group ( OR=0.389, 95% CI 0.248-0.610, P<0.001) ], and the lifting of COVID-19 restrictions ( OR=2.360, 95% CI 1.287-3.047, P<0.001) were independent factors influencing EBV IgM positivity in the general population. The EBV IgM positivity rate in individuals under 18 years old was not affected by gender or the lifting of COVID-19 restrictions when stratified by age group. Both genders ( OR=1.499, 95% CI 1.138 - 1.975, P=0.004) and the lifting of COVID-19 restrictions ( OR=2.608, 95% CI 1.940-3.507, P<0.001) were independent factors affecting EBV IgM positivity in the 18-50-year age group. The lifting of COVID-19 restrictions ( OR=2.222, 95% CI 1.101-4.484, P=0.026) was the sole independent factor affecting EBV IgM positivity in individuals over 50 years old. Conclusions:Previous infection rates of CMV and EBV are high in healthy populations in China, which increase with age. COVID-19 infection may increase EBV reactivation rates in healthy individuals, with a more pronounced effect on those aged >18 years.

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 This study aims to explore the formation of the dilemma of"giving care"for disabled elderly people in nursing homes from the perspective of active health.Methods Purposive sampling was used to select caregivers and disabled elderly people from a nursing home in Chongqing as research subjects from July 2022 to December 2022.One-on-one in-depth interviews were conducted and Colaizzi's 7-step thematic analysis method was employed to collect and analyze the interview data.Results 4 themes were identified:①the dominance of the"giving"care concept,including the cultural thoughts of filial piety,passive acceptance of care characteristics and consumer psychology regarding paid services;②insufficient"participation"care ability,including lack of knowledge regarding active health and a weakening of skills to promote participation;③the hindrance to"transformation"of care models,including objective limitations in terms of human resources and delays in adapting aging environments;and ④the decline in"utilization"of internal abilities,including excessive avoidance of potential risks,a heavy workload of care and poor quality of individual care.Conclusion The formation of the dilemma of"giving care"for disabled elderly people in nursing homes is affected by multiple factors such as social background,service system,supply resources,and management mode.Transforming disabled elderly individuals from a state of"passive giving care"to"active participation in their health"is an important measure to realize the concept of positive aging and healthy aging.

Objective:To construct an index system for evaluating the development of research-oriented disciplines in medical institutions, and to provide a basis for guiding the superior disciplines towards international high-level disciplines.Methods:Through literature research and expert discussions, the basic framework of the research-oriented disciplines development evaluation system was established. The final version of the index system was determined using the Delphi method and expert interviews, and the weights of each index were established using the hierarchical analysis method.Results:After consultation, the framework of 5 first-class indexes, 16 second-class indexes, and 51 third-class indexes was finally constructed for the evaluation system of research-oriented discipline development, and the weights of indexes at different classes were calculated. The high-frequency terms " research mechanism construction" , " research team construction" and " representative research results" extracted from the expert interviews echoed the results of the weighting calculation.Conclusions:The evaluation system for research-oriented disciplines constructed in this study is relatively reasonable, scientific, reliable, and operable. The construction of the index system adapts to the characteristics of the development of research-oriented disciplines, with guiding significance for enhancing the development of research-oriented disciplines.

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.