[Organ preservation in locally advanced colorectal cancer with microsatellite instability-high after immunotherapy].

Neoadjuvant immunotherapy has achieved exciting efficacy with high clinical complete response (cCR) and pathologic complete response (pCR) rates and durable long-term effects. PD-1 checkpoint blockade-based immunotherapy has been highly successful in microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) colorectal cancer and has been recommended as the first-line treatment for metastatic colorectal cancer by domestic and international guidelines. Several studies have shown that immunotherapy can be a potentially curable treatment for MSI-H rectal cancer and has even shown promise in organ preservation in colon cancer. In this study, we first clarified the feasibility of the watch-and-wait strategy after PD-1 checkpoint blockade treatment by indirect and direct evidence. Then from the assessment tools (including digital rectal examination, endoscopy, radiology, and lymph node assessment), the viable assessment methods of cCR for immunotherapy and related difficulties are proposed. Finally, the medication choices of immunotherapy, the treatment regimen, and the follow-up strategy are further discussed. We hope that neoadjuvant immunotherapy could be appropriately applied in MSI-H/dMMR colorectal cancer so that more patients can achieve organ preservation.

[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

[Healing effect of photodynamic therapy on extraction sockets of periodontally compromised teeth: a randomized, controlled, superiority clinical trial].

Objective: To evaluate the effects of photodynamic therapy (PDT) in extraction sockets of periodontally compromised molars on soft tissue healing, postoperative pain, bone density and bone height changes. Methods: This study is a single-center, single-blind, randomized controlled superiority clinical trial. Thirty-eight periodontally compromised molars requiring extraction in patients attending the Department of Periodontology, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, from December 2022 to September 2023 were included, and randomly assigned to PDT group and control group. The control group received routine debridement after extraction, while PDT group received routine debridement followed by PDT. The bucco-lingual and mesio-distal wound distances at 7 and 14 d after extraction were measured, and then the wound closure rates were calculated. Evaluating the soft tissue healing indexes at 7 and 14 d after extraction. The visual analogue scale was used to assess the pain level at 6 h, 1 d, 2 d, and 3 d after tooth extraction. Apical radiographs were taken immediately and 2 months after extraction in order to compare the changes of the bone density and height. Results: The wound closure rate at 1 week was (78.08±5.45)% in PDT group and (71.03±6.82)% in control group, with significant differences (P<0.01). The wound closure rate at 2 weeks in PDT group [(85.88±3.84) %] was significantly higher than that in the control group [(81.66±3.79) %] (P<0.01), but did not reach the superiority value of the superiority test (superiority value=10%, 95%CI at 1 week: 3.00%-11.12%, 95%CI at 2 weeks: 1.71%-6.73%). The soft tissue healing index of PDT group at 1 week was significantly better than the control group (P<0.05), but there was no significant difference between the two groups at 2 weeks (P>0.05). There was no significant difference between the two groups in terms of postoperative pain at 6 h, 1 d, 2 d and 3 d as well as in bone density and height changes at 2 months after tooth extraction (P>0.05). Conclusions: PDT could promote soft tissues healing to some extent, but did not provide additional assistance in the healing of extraction sockets of periodontally compromised teeth. PDT did not show benefits on postoperative pain, changes of the bone density and bone height after tooth extraction.

[Relationship between sleep status and occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China].

Objective: To understand the prevalence of occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China, and analyze the relationship between their sleep status and occasional hypertension. Methods: From October to November 2017, a total of 24 842 preschool children from 109 kindergartens in 11 cities in Hubei, Anhui and Jiangsu provinces were selected by intentional sampling method. A self-made questionnaire was used to collect basic information about the subjects, and the sleep status data was collected by the Children's Sleep Habits Questionnaire. Physical examinations were performed on the subjects, and height, weight and blood pressure were measured on-site. The difference in occasional hypertension detection rate among preschool children with different characteristics was compared, and the correlation between sleep status and occasional hypertension detection rate was analyzed by the multivariate logistic regression model. Results: The age of the subjects was (4.4±1.0) years, including 12 729 boys (51.2%). The prevalence of occasional hypertension was 31.8% (7 907/24 842). The prevalence of occasional hypertension among preschool children in three provinces of the middle and lower reaches of the Yangtze River was 31.8%. There were statistically significant differences in the detection rate of occasional hypertension among preschool children of different genders, age groups, family residence, family economic status and parents' education level (all P values<0.05). The detection rate of occasional hypertension in children with less than 10 hours of sleep was higher than those with sufficient sleep, and the difference was statistically significant (P<0.05). The results of multivariate logistic regression analysis showed that after adjusting for factors such as gender, age, family residence, family economic status, parental education level, parental smoking history, and physical constitution, the ORs (95%CI) for less than 10 hours of sleep, turning on the lights while sleeping, and poor sleep quality were 1.09 (1.03-1.15), 1.17 (1.07-1.28) and 1.04 (0.91-1.18), respectively, compared with the corresponding reference group. Conclusion: The detection rate of occasional hypertension is high in preschool children in the middle and lower reaches of the Yangtze River and there is a positive correlation between insufficient sleep and turning on the light when sleeping and occasional hypertension in preschool children.

[Survival analysis on HIV/AIDS cases newly received antiretroviral therapy who coinfected with hepatitis B virus in Jiangsu Province, 2005-2020].

Objective: To analyze the incidence of co-infection of HIV and HBV and death in HIV/AIDS cases who newly received antiretroviral therapy (ART) from 2005-2020 in Jiangsu Province. Methods: According to the baseline and follow-up data of HIV/AIDS cases on ART enrolled between January 2005 and December 2020, the last follow-up clinical visit was up until December 31, 2022, the national information system was retrospectively collected for HIV/AIDS cases from Chinese System Disease for Control and Prevention. Excel database was established, and statistical analysis was performed using the SPSS 16.0 software. Kaplan-Meier method was used to draw the survival curves, the log rank test was used to compare the survival curves, and Cox proportional hazards modeling was used to assess the mortality and potential risk factors. Results: There were 33 322 HIV/AIDS cases that newly received ART during 2005-2020.The rate of HBsAg test was 57.3%(19 098/33 322). Among HIV/AIDS cases tested HBsAg, the ratio of male to female was 7.1∶1 (16 745∶2 353), the average age was (39.4±14.0) years old, 49.5% (9 446/19 098) of the HIV/AIDS cases were married, 57.8% (11 048/19 098) were infected with HIV through homosexual contact and 36.6% (6 990/19 098) were through heterosexual contact. The M (Q1, Q3) of CD4+T lymphocytes (CD4) counts at ART initiation was 297 (166, 445) cells/µl. A total of 8.2% (1 566/19 098, 95%CI:7.8%-8.6%) were HBsAg positive. There were 1 062 HIV/AIDS died by December 31, 2022. The log rank test showed that there were differences in survival curves between HIV/AIDS co-infected with HBV or not (χ2=28.07, P<0.001). Multivariate analysis of the Cox proportional risk regression model showed that enrollment year, age, marital status, route of HIV infection, baseline CD4 counts before ART, and co-HBV infection were the influencing factors for HIV/AIDS death (all P<0.05), compared with those enrolled in 2015 and before, age ≥45 years, and those who were unmarried. Those enrolled in treatment from 2016 to 2020, those younger than 45 years, and married/cohabitation had a lower risk of death. Compared with baseline CD4 counts ≥201 cells/µl, other routes of infection, and HIV infection alone, baseline CD4 counts ≤200 cells/µl, injecting drug use, and co-HBV infection were associated with a higher risk of death. Conclusion: Effective treatment for coinfection with HBV and HBV vaccination for HBV-negative people with HIV should be integrated into HIV treatment programs to reduce HIV-related mortality in Jiangsu Province, 2005-2020.

Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.

Periodontitis (PD) is the primary cause of tooth loss in adults. Porphyromonas gingivalis (P.g), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that P.g-induced pyroptosis was activated in macrophages, with Casp11 deficiency attenuating these effects. In an experimental PD mouse model, Casp11 deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. Casp11-/- mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, Casp11 deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.

[Identification model of tooth number abnormalities on pediatric panoramic radiographs based on deep learning].

Objective: To identify tooth number abnormalities on pediatric panoramic radiographs based on deep learning. Methods: Eight hundred panoramic radiographs of children aged 4 to 11 years meeting the inclusion and exclusion criteria were selected and randomly assigned by writing programs in Python (version 3.9) to the training set (480 images), verification set (160 images) and internal test set (160 images), taken in Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between November 2012 to August 2020. And all panoramic radiographs of children aged 4 to 11 years taken in the First Outpatient Department of Peking University School and Hospital of Stomatology from June 2022 to December 2022 were collected as the external test set (907 images). All of the 1 707 images were obtained by operators to determine the outline and to label the tooth position of each deciduous tooth, permanent tooth, permanent tooth germ and additional tooth. The deep learning model with ResNet-50 as the backbone network was trained on the training set, validated on the verification set, tested on the internal test set and external test set. The images of test sets were divided into two categories according to whether there was abnormality of tooth number, to calculate sensitivity, specificity, positive predictive value and negative predictive value, and then divided into four types of extra teeth and missing permanent teeth both existed, extra teeth existed only, missing permanent teeth existed only, and normal teeth number, to calculate Kappa values. Results: The sensitivity, specificity, positive predictive value and negative predictive value were 98.0%, 98.3%, 99.0% and 96.7% in the internal test set, and 97.1%, 98.4%, 91.9% and 99.5% in the external test set respectively, according to whether there was abnormality of tooth number. While images were divided into four types, the Kappa value obtained in the internal test set was 0.886, and that in the external test set was 0.912. Conclusions: In this study, a deep learning-based model for identifying abnormal tooth number of children was developed, which could identify the position of additional teeth and output the position of missing permanent teeth on the basis of identifying normal deciduous and permanent teeth and permanent tooth germs on panoramic radiographs, so as to assist in diagnosing tooth number abnormalities.

[Clinical and radiographic effect of simultaneously labial and lingual augmented corticotomy: a prospective case series study].

Objective: To investigate soft-and hard-tissue changes after simultaneously labial and lingual augmented corticotomy in patients with insufficient alveolar bone thickness of lower anterior teeth both in labial and lingual side during orthodontic treatment. Methods: From January 2021 to June 2022, 10 patients [2 males and 8 females, (26.2±3.1) years old] who received orthodontic and orthognathic combined treatment from the Fourth Clinical Division, Peking University School and Hospital of Stomatology were selected. The alveolar bone thickness of lower anterior teeth both in labial and lingual side in these patients was less than 0.5 mm according to cone-beam CT examination before or during treatment, and 60 lower anterior teeth were included. The 10 patients were treated with simultaneously labial and lingual augmented corticotomy. The differences in gingival recession, papilla index and the differences in labial and lingual alveolar bone thickness of lower anterior teeth were compared. Results: Six months after surgery, the alveolar bone thicknesses at the 4 mm under cemento-enamel junction (CEJ), 8 mm under CEJ and at the apical level [labial side: (1.02±0.39), (2.22±0.89) and (4.87±1.35) mm; lingual side: (1.07±0.46), (2.31±1.04) and (3.91±1.29) mm] were significantly higher than that before surgery [labial side: (0.02±0.09), (0.06±0.21) and (2.71±1.33) mm]; lingual side: (0.14±0.29), (0.40±0.52) and (2.13±1.02) mm] (P<0.001), respectively. The increases in alveolar bone thickness of central incisors [apical level on labial side: (2.53±1.20) mm, 8 mm under CEJ on lingual side: (2.27±1.24) mm, apical level on lingual side: (2.66±1.49) mm] and lateral incisors [apical level on labial side: (2.42±1.30) mm, 8 mm under CEJ on lingual side: (2.28±0.92) mm, apical level on lingual side: (1.94±1.15) mm] were significantly higher than that of canines [apical level on labial side: (1.52±1.47) mm, 8 mm under CEJ on lingual side: (1.17±1.09) mm,apical level on lingual side: (0.74±1.37) mm] (P<0.01). There were no significant differences in the degree of gingival recession [labial side before surgery: (0.72±0.88) mm, lingual side before surgery: (0.80±1.09) mm; labial side 6 months after surgery: (0.72±0.81) mm,lingual side 6 months after surgery: (0.89±0.21) mm] and gingival papilla index [before surgery: 1.00(0.75, 2.00); 6 months after surgery: 1.00(1.00, 2.00) ] between pre-operation and 6 months after surgery (P>0.05). No serious complications occurred. Conclusions: The method used in this article for simultaneously labial and lingual augmented corticotomy was safe and feasible. This surgery has positive clinical significance for the stability of the periodontal tissue in orthodontic treatment for patients with alveolar bone thickness less than 0.5 mm of lower anterior teeth both in labial and lingual side.

[Standardized nomenclature of oral microorganisms in Chinese: the 2023 update].

Oral microbial community, as an important part of human microbial community, is closely related to oral and general health. Oral microbiological research has become the forefront of international microbiological research. Standardized and unified nomenclature for oral microorganisms in Chinese is of great significance to support the development of oral medicine research. Standardized translation of microbial names is the basis for writing canonical and authoritative professional textbooks and reference books, which helps students to accurately acquire the characteristics and classifications of oral microbes. Unified translation of oral microorganisms is also conducive to academic communication and cooperation, and plays an important role in oral health education and science popularization, which enables oral microbiology knowledge to be accurately disseminated to the public. Therefore, in order to standardize the words in scientific research, funding application, publications, academic exchanges and science popularization within the field of oral medicine, we have fully discussed and revised the Chinese names of oral microorganisms in 2017 edition and ones of newly discovered oral microbes, finally reaching a consensus to form the 2023 edition of Chinese names of oral microorganisms.

Association between Malnutrition and Delirium in Older Chronic Kidney Disease Patients Admitted to Intensive Care Units: A Data Linkage Study.

BACKGROUND: Independently, malnutrition and delirium in older hospitalised adults is prevalent. However, there is limited evidence on the association between these two conditions in older hospitalised adults with chronic kidney disease (CKD). OBJECTIVES: To determine the association between malnutrition and delirium in older CKD patients admitted to intensive care units (ICU). METHODS: This data linkage study utilised administrative data from New South Wales (NSW) hospitals in Australia between 2017 and 2020.Admitted patient data was linked with Cause of Death Unit Record File, and NSW Registry of Deaths (RBD). The study population comprised all CKD patients aged 65 and over admitted to ICUs. Descriptive statistics were used to summarise patient characteristics. Binary logistic tested for association between malnutrition and delirium. RESULTS: The study population included 748 CKD patients with a total 948 admissions in the study period. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) was used to code for all outcomes and comorbidities. The incidence of delirium was 15.5% (n=141) and malnutrition was recorded in 11.3% (n=103) across all admissions. The adjusted odds ratio (OR) of a delirium diagnosis was 2.07 (95% CI: 1.27-3.39) for CKD patients that were malnourished compared to non-malnourished CKD patients. CONCLUSIONS: This study showed a significant association between delirium and malnutrition in older CKD patients admitted to ICU. Management of malnutrition could be critical in reducing the risk of delirium in older hospitalized patients with CKD. Additionally, more education and awareness around delirium and its association with malnutrition are needed in clinical practice.

Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

[Independent and joint effect of chronotype and sleep duration on self-rated health in medical students].

Objective: To investigate the independent and joint effects of chronotype and sleep duration on self-rated health in medical students. Methods: A cross-sectional study was conducted in 1 526 medical students selected through proportional stratified cluster random sampling from a medical university in Zhejiang province. A questionnaire survey was conducted to collect the information about their basic demographic characteristics, chronotype, sleep duration, and other lifestyle factors such as midnight snack, sedentary behavior, physical activity, meal time, and self-rated health. The independent and joint effects of chronotype and sleep duration on self-rated health were assessed by logistic regression model after controlling for confounding variables. Results: The numbers of the students with evening chronotype, neutral chronotype, and morning chronotype were 664 (43.5%), 442 (29.0%), and 420 (27.5%), respectively. Among the medical students, 42.8% (653) had poor self-rated health. Compared with those with the morning chronotype, the adjusted ORs for those with neutral chronotype and evening chronotype were 1.69 (95%CI: 1.23-2.31) and 2.43 (95%CI: 1.81-3.26), respectively, trend test P<0.001. Compared with those with sleep duration of 8 h or above per night, the adjusted ORs for those with sleep duration of 7 and ≤6 h per night were 1.40 (95%CI: 1.07-1.84) and 2.38 (95%CI: 1.69-3.37), respectively, trend test P<0.001. In the joint effect, compared with those with the morning chronotype and sleep duration of 8 h or above per night, the adjusted OR for those with evening chronotype and sleep duration of ≤6 h per night was 6.53 (95%CI: 3.53-12.09). Conclusions: Both evening chronotype and insufficient sleep were associated with increased odds of poor self-rated health in medical students, and they had joint effects. Therefore, it is necessary to promote early to bed, early to rise and adequate sleep in medical student to maintain their health.

[Immunotherapy for microsatellite-instability-high advanced colorectal cancer].

Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.

[Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer].

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

Search for Active-Sterile Antineutrino Mixing Using Neutral-Current Interactions with the NOvA Experiment.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

[Analysis on HIV and hepatitis B virus coinfection in HIV/AIDS cases newly received highly active antiretroviral therapy in Jiangsu province, 2005-2019].

Objective: To analyze the HIV and HBV coinfection in HIV/AIDS cases who newly received highly active antiretroviral therapy during 2005-2019 in Jiangsu province. Methods: According to the base data of HIV/AIDS cases on HAART enrolled between January 2005 and December 2019; the National Information system was retrospectively collected for HIV/AIDS Control and Prevention of Chinese System Disease for Control and Prevention. Excel database was established, and statistical analysis was performed using the SPSS 16.0 software. A Chi-square test was used to assess differences in rates of HBsAg testing and HIV/HBV coinfection between potential risk factors. The unconditional logistic regression model entered risk factors with P values <0.05 in the Chi-square test. Results: There were 29 288 HIV/AIDS cases newly received HAART during 2005-2019. The rate of HBsAg test was 49.8% (14 594/29 288) the rate of HBsAg test increased from 0.0% (0/80)to 75.2%(3 448/4 586), showing an increasing trend year by year during 2005 to 2019. Among HIV/AIDS cases tested HBsAg, 81.6% (11 915/14 594) cases were from Jiangsu province; the ratio of male to female was 7.34∶1 (12 845∶1 749), the average age was (38.5±13.8) years old, 96.1% (14 023/14 594) were Han nationality,48.9% (7 131/14 594) of the HIV/AIDS cases married, 97.9%(14 294/14 594) were infected with HIV through homosexual and heterosexual transmission. Unconditional logistic regression modeling showed that the proportion of HIV/AIDS cases initiated HAART in 2015 or after that, married, not Jiangsu province resident, college education or above, and drug injection infected were more likely to have HBsAg testing. 8.6%(95%CI:8.2%-9.1%) were HBsAg positive. The HIV and HBV coinfection rates were more than 10% before 2016 while showed stability from 6.7% to 8.2% since 2016. Unconditional logistic regression modeling showed that the proportion of HIV/AIDS cases who were male, elder, married, non-Han, primary education or below were more likely to have HBV coinfection. Conclusion: More HBsAg testing should be strengthened when the HIV/AIDS cases initiated HAART in Jiangsu province, 2005-2019.

[The clinical value of further accurate staging of pT2 gastric cancer based on the depth of invasion].

Objective: To investigate the clinical value of pT2 gastric cancer staging pT2a and pT2b according to the depth of muscularis propria invasion in evaluating the prognosis of gastric cancer. Methods: According to the 8th edition of TNM staging system for gastric cancer proposed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), patients with gastric cancer who underwent radical surgery in the Fourth Hospital of Hebei Medical University from January 1, 2008 to January 1, 2015 were selected and divided into pT2a and pT2b stage group according to the depth of tumor invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Results: The median follow-up time of 1 411 patients with postoperative pathological pT2 stage was 68.8 months, and 1 347 patients (95.46%) received complete follow-up data. The 5-year OS rate was 65.85%, and the 5-year DFS rate was 67.83 %. The 5-year OS rate and 5-year DFS rate of 709 pT2a patients were 72.50% and 73.91%, respectively. The 5-year OS rate and 5-year DFS rate of 638 pT2b patients were 58.46% and 61.13%, respectively, significantly different from those of the pT2a group (P<0.001). Hierarchical analysis was performed according to N staging. The 5-year OS rates of pT2aN0M0 (274 cases), pT2aN1M0 (192 cases), pT2aN2M0 (147 cases), pT2aN3aM0 (59 cases) and pT2aN3bM0 (37 cases) were 83.58 %, 72.40 %, 68.71 %, 54.24 % and 35.12 %, respectively. The 5-year DFS rates were 84.67 %, 77.08 %, 67.35 %, 54.24 % and 35.14 %, respectively. In the pT2b group, the 5-year OS rates of pT2bN0M0 (209 cases), pT2bN1M0 (166 cases), pT2bN2M0 (127 cases), pT2bN3aM0 (78 cases) and pT2bN3bM0 (58 cases) were 76.08%, 62.05%, 56.69%, 37.18% and 17.24%, respectively, and the 5-year DFS rates were 80.86%, 69.28%, 54.33%, 35.90% and 15.52%, respectively. Under the same N stage, the OS rates of patients in the pT2a group were better than those in the pT2b group (P values were 0.023, 0.034, 0.034, 0.043 and 0.018, respectively). When the N stage was N0 and N1, there was no significant difference in the 5-year DFS rate between the pT2a group and the pT2b group (P values were 0.199 and 0.090, respectively). When the N stages were N2, N3a and N3b, the difference between the pT2a stage group and the pT2b stage group was statistically significant (P values were 0.027, 0.022 and 0.025, respectively). Conclusions: In the 8th edition of AJCC/UICC gastric cancer staging system, pT2 stage can be divided into pT2a stage (invasion of superficial muscularis) and pT2b stage (invasion of deep muscularis) according to the infiltration depth of muscularis propria. There are significant differences in prognosis between the two groups. Combined with the number of lymph node metastasis, the prognosis of patients with pT2 gastric cancer can be more accurately evaluated.

[Advances in research of pyroptosis in the mechanism of periodontal disease].

Pyroptosis is a pro-inflammatory form of programmed cell death that has been gradually recognized in recent years. It plays an important role in recognizing the invasion of exogenous pathogens and sensing endogenous danger signals. The initiation of pyroptosis depends on the activation of intracellular inflammasome and its downstream caspases, as well as the active fragment of the key protein Gasdermin. The invasion of periodontal pathogens induces an inflammatory response of the host, involving the activation of inflammasome and triggering pyroptosis as well. Meanwhile, it leads to the release of a large number of inflammatory cytokines such as interleukin (IL)-1ß and IL-18 to amplify the inflammatory response and mediate periodontal tissue destruction eventually. This article reviews the research progress of the signaling pathways of pyroptosis, as well as its mechanism induced by periodontal pathogens and the mechanism of periodontal tissue damage in periodontitis in order to provide new targets and ideas for the prevention and treatment of periodontitis.

[The effect of cancer nodules on survival prognosis of gastric cancer patients].

Objective: To explore the relationship between cancer nodules and clinicopathological characteristics of gastric cancer, and analyze its impact on survival prognosis of gastric cancer patients. Methods: A retrospective analysis of 2 386 patients with gastric cancer who underwent radical surgery from January 1, 2012 to January 1, 2015 in the Third Surgery Department of the Fourth Hospital of Hebei Medical University was performed. The relationship between cancer nodules and clinicopathological characteristics of gastric cancer and its impact on survival prognosis of gastric cancer patients were analyzed. Results: Among the 2 386 patients, there were 459 cases (19.24%) with cancer nodules, and 1 927 cases (80.76%) without cancer nodules. Logistic multivariate analysis showed that pT staging (P=0.036), pN staging (P=0.024), pTNM staging (P=0.032), Borrmann classification (P=0.008), vascular tumor thrombus (P=0.001) were independent risk factors for cancer nodules. The complete follow-up date of 2 273 cases (95.26%) of 2 386 patients with gastric cancer were obtained. A total of 1 259 patients relapsed and 1 152 died during the follow-up period. The 5-years overall survival (OS) rate was 49.32%, and the 5-years disease-free survival (DFS) rate was 44.61%. Among them, the 5-years OS rate and DFS rate of those with cancer nodules were 26.76% and 24.94%, while the 5-years OS rate and DFS rate of those without cancer nodules were 54.75% and 49.34%, respectively (P<0.001). Patients with positive cancer nodules were divided into 3 groups according to the number of cancer nodules: 1 (115 cases), 2 to 3 (202 cases), and more than 4 (124 cases). The 5-years OS rates of 3 groups were 41.74%, 30.69% and 10.48%, respectively (P<0.001). The 5-years DFS rates were 40.00%, 28.22% and 9.68%, respectively (P<0.001). Cox multivariate analysis showed that histological type (P=0.004), pT staging (P=0.007), pN staging (P=0.004), pTNM staging (P=0.002), vascular tumor thrombus (P=0.034), cancer nodules (P=0.005) and the number of cancer nodules (P=0.001) were independent risk factors for the prognosis of gastric cancer patients, and postoperative adjuvant chemotherapy (P=0.043) was a protective factor for the prognosis of gastric cancer patients. Conclusion: Cancer nodules are closely related to the tumor stage and prognosis of gastric cancer patients. The number of cancerous nodules is an independent risk factor for the prognosis of gastric cancer patients.