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 Some epidemiological studies have shown that pregnant women who develop preeclampsia(PE)have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy,revealing a potential association between hyperandrogenism in women and PE.To explore the causal relationship between hyperandrogenism and PE,this study selected total testosterone(TT),bioavailable testosterone(BIOT),and sex hormone binding globulin(SHBG)as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes.Two-sample Mendelian randomization(MR)analyses were used to genetically dissect the causal relationships between the three exposure factors(TT,BIOT,and SHBG)and the outcomes of PE and chronic hypertension with superimposed PE.Methods Two independent genome-wide association study(GWAS)databases were used for the two-sample MR analysis.In the GWAS data of female participants from the UK Biobank cohort,single nucleotide polymorphisms(SNPs)associated with TT,BIOT,and SHBG were analyzed,involving 230 454,188 507,and 188 908 samples,respectively.GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP,involving 3 556 PE cases and 114 735 controls,as well as 38 cases of chronic hypertension with superimposed PE and 114 735 controls.To meet the assumptions of instrumental relevance and independence in MR analysis,SNPs associated with exposure were identified at the genome-wide level(P<5.0×10-8),and those in linkage disequilibrium interference were excluded based on clustering thresholds of R2<0.001 and an allele distance greater than 10 000 kb.Known confounding factors,including previous PE,chronic kidney disease,chronic hypertension,diabetes,systemic lupus erythematosus,or antiphospholipid syndrome,were also identified and the relevant SNPs were removed.Finally,we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS,integrating exposure and outcome data,and removing palindromic sequences.Five genetic causal analysis methods,including inverse variance-weighted method(IVW),MR-Egger regression,weighted median method,simple mode method,and weighted mode method,were used to infer causal relationships.In the IVW,it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect.IVW was consequently used as the primary analysis method in this study.Considering the potential heterogeneity among the instrumental variables,random-effects IVW was used for MR analysis.The results were interpreted using odds ratios(OR)and the corresponding 95% confidence interval(CI)to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE.If the CI did not include 1 and had a P value less than 0.05,the difference was considered statistically significant.Sensitivity analysis was conducted to assess heterogeneity and pleiotropy.Heterogeneity was examined using Cochran's Q test,and pleiotropy was assessed using MR-Egger intercept analysis.Additionally,leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations.To further validate the findings,MR analyses were performed using the same methods and outcome variables,but with different exposure factors,including waist-to-hip ratio adjusted for BMI(WHRadjBMI)and 25-hydroxyvitamin D levels,with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls.Results According to the criteria for selecting genetic instrumental variables,186,127,and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT,BIOT,and SHBG.MR analysis did not find a causal relationship between the TT,BIOT,and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE.The IVW method predicted that genetically predicted TT(OR[95% CI]=1.018[0.897-1.156],P=0.78),BIOT(OR[95% CI]=1.11[0.874-1.408],P=0.392),and SHBG(OR[95% CI]=0.855[0.659-1.109],P=0.239)were not associated with PE.Similarly,genetically predicted TT(OR[95% CI]=1.222[0.548-2.722],P=0.624),BIOT(OR[95% CI]=1.066[0.242-4.695],P=0.933),and SHBG(OR[95% CI]=0.529[0.119-2.343],P=0.402)were not significantly associated with chronic hypertension with superimposed PE.Additionally,MR analysis using the MR-Egger method,weighted median method,simple mode method,and weighted mode method yielded consistent results,indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE.Heterogeneity was observed for SHBG in the analysis with PE(Cochran's Q test,P=0.01),and pleiotropy was detected for BIOT in the analysis with PE(MR-Egger intercept analysis,P=0.014),suggesting that the instrumental variables did not affect PE through BIOT.Other instrumental variables did not show significant heterogeneity or pleiotropy.Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables.Consistent with previous MR studies,the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study.Conclusion The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT,BIOT,and SHBG levels and the development of PE and chronic hypertension with superimposed PE.This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.

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.