Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Oral cancer is one of the most prevalent malignant tumors of the head and neck region.In China,the incidence of oral cancer ranks second among all cancers of the head and neck and second only to that of nasopharyngeal carcinoma.More than 50%of patients with oral cancer are either at a locally advanced stage at initial diagnosis or have already developed distant metastasis.Depending on the cancer stage in a patient,multidisciplinary treatment,including surgery,radiotherapy,chemotherapy,immunotherapy,and targeted therapy,is cur-rently the standard treatment for oral cancer.Despite the variety of treatment modalities,the 2-/5-year overall survival rate of patients with oral cancer is rather low and cannot meet clinical needs.Therefore,there is an urgent need to develop more effective and comprehensive treatment modalities to improve the prognosis of oral cancer.In this study,we reviewed a new multidisciplinary comprehensive treatment mode for oral cancer in recent years and the progress in radiotherapy for oral cancer under this new mode.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC.
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Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proteolysis ; Proto-Oncogene Proteins p21(ras)/genetics*

The phosphosphatidylinositol-3-kinase (PI3K) signaling pathway is one of the most important intracellular signal transduction pathways affecting cell functions, such as apoptosis, translation, metabolism, and angiogenesis. Lung cancer is a malignant tumor with the highest morbidity and mortality rates in the world. It can be divided into two groups, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for >85% of all lung cancers. There are currently many clinical treatment options for NSCLC; however, traditional methods such as surgery, chemotherapy, and radiotherapy have not been able to provide patients with good survival benefits. The emergence of molecular target therapy has improved the survival and prognosis of patients with NSCLC. In recent years, there have been an increasing number of studies on NSCLC and PI3K signaling pathways. Inhibitors of various parts of the PI3K pathway have appeared in various phases of clinical trials with NSCLC as an indication. This article focuses on the role of the PI3K signaling pathway in the occurrence and development of NSCLC and summarizes the current clinical research progress and possible development strategies.

Objective:To investigate the hemodynamic changes of the main arteries and veins of the extremities and the heart in patients with hypertrophic scar secondary to extensive burns after pressure treatment, and to analyze the relevant mechanisms.Methods:A retrospective before-after self-control study was conducted. From January 2017 to February 2022, 37 patients with hypertrophic scar secondary to extensive burns who met the inclusion criteria were hospitalized in the Burn Rehabilitation Department of Guangdong Industrial Injury Rehabilitation Hospital, including 25 males and 12 females, aged 23-52 years. The patients were admitted to the hospital within 12 weeks after wound healing, and within one week after admission, rehabilitation therapists, occupational therapists, and tailors custom-made pressure products such as full-body pressure garment, pressure pants, vests, split finger gloves, split finger socks, hoods, and plastic collars, with the pressure at each part maintained at 2.67-4.00 kPa when wearing. Before the first treatment with pressure products (hereinafter referred to as before pressure treatment) and at 1 h of the first treatment with pressure products (hereinafter referred to as 1 h of pressure treatment), color Doppler ultrasonography was performed to check the pulse rate of the axillary artery, the lumen diameter, peak systolic velocity (PSV), and resistance index of the axillary artery and femoral artery on the left side, the lumen diameter, cross-sectional area, and average blood flow velocity of the axillary vein and femoral vein, and the mitral valve E peak, mitral valve A peak, tricuspid valve E peak, aortic valve PSV, and pulmonary valve PSV of the heart; an optical chromatographic skin detector was used to detect the red color, red pigment, and surface brightness of the scar on the back of the hand to reflect the filling and distribution of the scar microvessels. Data were statistically analyzed with paired sample t test. Results:Compared with those before pressure treatment, the PSV of the axillary artery of patients was significantly slowed down at 1 h of pressure treatment ( t=55.42, P<0.01); the average blood flow velocity of the axillary vein was significantly accelerated ( t=-60.50, P<0.01); the pulse rate, lumen diameter, and resistance index of the axillary artery, as well as the lumen diameter and cross-sectional area of the axillary vein did not change obviously ( P>0.05); the average blood flow velocity of the femoral vein was significantly accelerated ( t=-80.52, P<0.01); the lumen diameter, PSV, and resistance index of the femoral artery, as well as the lumen diameter and cross-sectional area of the femoral vein had no significant change ( P>0.05); the mitral valve E peak and mitral valve A peak of the heart decreased significantly (with t values of 10.71 and 21.96, respectively, P<0.01); the tricuspid valve E peak of the heart increased significantly ( t=7.57, P<0.01); the PSV of the aortic valve and pulmonary valve of the heart did not change obviously ( P>0.05). At 1 h of pressure treatment, the red color and red pigment values of the scar on the back of the hand of patients were 15.3±1.1 and 16.8±1.2, respectively, which were significantly lower than 24.5±1.3 and 23.8±1.2 before pressure treatment (with t values of 8.32 and 8.04, respectively, P<0.01). The brightness value of the scar surface on the back of the hand of patients at 1 h of pressure treatment was similar to that before pressure treatment ( P>0.05). Conclusions:After pressure treatment for the hypertrophic scar in patients secondary to extensive burn, the average blood flow velocity of the axillary vein and femoral vein in patients are obviously accelerated, the PSV of the axillary artery is significantly slowed down, the peak values of mitral valve E and mitral valve A of the heart are significantly decreased, and the tricuspid valve E peak is significantly increased. These hemodynamic changes may be related to the reduction of microvascular blood flow in the local area of scar after systemic pressure treatment.

Objective:To evaluate the 3-year survival outcomes and late injury between the self-designed patent single-channel applicator, which was modified from the traditional tandem applicator and wrapped with a oval-shield alloy around the source channel and standard Fletcher-type applicator in the high-dose-rate brachytherapy for cervical cancer.Methods:Patients initially diagnosed with cervical cancer in the Affiliated Hospital of Southwest Medical University from December 2011 to April 2017 were enrolled and randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. The whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (Equivalent Dose in 2 Gy at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m 2 once weekly during EBRT. Clinical efficacy and safety were evaluated after corresponding treatment. Results:In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. Up to December 2020, all patients had been followed up for 3 years, and the median duration of follow-up was 61 months. In the Fletcher group, the 3-year overall survival, progression-free survival and locoregional failure-free survival was 76.3%, 78.1% and 75.4%, and 83.8%, 80.3% and 85.5% in the single-channel group, respectively. In the Fletcher group, the cumulative rate of grade 3-4 late rectal complications was 3.3% and 6.7% in the single-channel group ( P=0.122). The cumulative rate of grade 3-4 bladder complications was 1.3% in the Fletcher group and 0.7% in the single-channel group ( P=1.000). Conclusion:The self-designed patent single-channel intracavitary applicator yields equivalent long-term clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer.

Objective: To explore the relationship between parents’ unstable marital status and offspring’s suicide attempts and the possible mediating factors, and to provide reference for suicide prevention among off spring grom unst able families. Methods: From 2017 to 2018, 2 766 valid questionnaires were collected from freshmen in a university in Hunan province. Students completed questionnaires of childhood trauma and depression traits,and reported their parents’ marital status and suicide attempts etc. Results: Compared to college students with parents of stable marital status,students with parents of unstable marital status showed higher reported rate of suicide attempts and higher scores of depression trait and childhood trauma (t/χ2=2.78, 5.83, 20.30, P<0.05). Controlling possible confounding factors,unconditional Logistic regression showed that childhood trauma,unstable marital status of parents and depressive traits were positively correlated with suicide attempt(OR=1.05, 1.45, 1.08, P<0.05). The 95% confidence interval of the Bootstrapping method with four mediation pathways (parental marital status→childhood trauma→depressive trait,childhood trauma→depressive trait→suicide attempt,parental marital status→childhood trauma→suicide attempt and parental marital status→childhood trauma→depressive trait→suicide attempt) does not include zero. Conclusion Childhood trauma and depressive traits mediate the relationship between parental instable marriage and suicide attempts in off spring.

Objective:To study the application and effect of hybrid teaching based on the rain classroom in the teaching of periodontology for undergraduates.Methods:Sixty-four stomatological undergraduates in Phase 101 were selected as experimental group, and 62 in Phase 100 as control group. The hybrid teaching based on the rain classroom were conducted in experimental group, and mind mapping were used before and after class to help students understand and expand the content of class. The traditional teaching was adopted in the control group. SPSS 17.0 was applied to compare the differences between the written test scores and teaching satisfaction evaluation of the two groups. The learning behavior data of the students in experimental group before, during and after class were collected and analyzed.Results:The score of the written test in the experimental group were significantly better than that in the control group ( t=2.97, P<0.05). The result of questionnaire showed that the experimental group was significantly more satisfied with the improvement of lecture efficiency ( t=2.71, P<0.05) and self-learning ability ( t=4.35, P<0.05). The majority (82.55%) of students in the experimental group are in favor of the rain classroom; 89.06% of students finished the preview before class, and 67.19% of them completed the review after class. Conclusion:The hybrid teaching based on the rain classroom can be applied to the teaching of periodontology, which can effectively improve the learning quality and initiative of the students.

Objective:To investigate the clinical, pathological and genetic characteristics of neonatal alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV).Methods:The clinical manifestations, radiographic examinations, pathology and parental genetic analysis of a newborn with FOXF1 variation induced ACDMPV, who was hospitalized in the Department of Neonatology of Shenzhen Children′s Hospital in January 2020, were extracted and analyzed. Related literature up to March 2020 with the key words of “Alveolar capillaries dysplasia” “Alveolar capillary dysplasia with misalignment of the pulmonary veins” “FOXF1” in PubMed, CNKI, Wanfang, CQVIP database and Leiden Open Variation database (LOVD) were searched.Results:A full-term male newborn （1 hour of age） was admitted due to anal atresia. Surgical repair of anal atresia and omphalocele was performed on the first day of life, and gallbladder absence and Meckel′s diverticulum were identified during the operation. Respiratory distress with hypoxemia developed at about 6 hours of life, and persistent pulmonary hypertension developed and progressed after surgery, with poor response to mechanical ventilation and pulmonary vasodilators. This infant passed away at 26 days of life. Lung biopsy showed decreased alveolar units and thickened interalveolar septa, reduced alveolar capillary density and thickened walls of peripheral pulmonary arteries, and misaligned pulmonary veins adjacent to the pulmonary arterioles, which were consistent with ACDMPV. The whole exome sequencing revealed a heterozygous novel frameshift of FOXF1 gene located in chromosome 16q24.1 c376_377insT; p.(Pro126fs). According to the bioinformatics analysis, this variation was likely to be pathogenic as it was associated with coding disorder of FOXF1 Pro126, resulting in truncation of the encoded protein. This novel variation had not been reported in the human gene mutation database (HGMD), ESP6500siv2_ALL, 1000g2015aug_ALL or dbSNP147 database. Previous 6 literatures reported 54 variants, including 28 missense, 10 nonsense, 11 frameshift, 2 deletion, 1 synonymous, and 2 extensions. Only three of the reported 45 cases （24 males, 21 females） were still alive as of the time of this study.Conclusions:Typically, ACDMPV is a catastrophic disease in neonatal period with high mortality. Lung biopsy and genetic testing should be considered in infants who present with persistent pulmonary hypertension and refractory hypoxemia, especially when combined with extrapulmonary abnormalities.