Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions / 医学前沿

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

Clinical analysis of combined immunotherapy in patients with malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.

Efficacy of intramuscular injection of Xiyanping injection for the treatment of acute bronchitis in children: a multicenter, randomized, parallel-controlled clinical study / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of Xiyanping injection through intramuscular injection for the treatment of acute bronchitis in children.@*METHODS@#A prospective study was conducted from December 2021 to October 2022, including 78 children with acute bronchitis from three hospitals using a multicenter, randomized, parallel-controlled design. The participants were divided into a test group (conventional treatment plus Xiyanping injection; n=36) and a control group (conventional treatment alone; n=37) in a 1:1 ratio. Xiyanping injection was administered at a dose of 0.3 mL/(kg·d) (total daily dose ≤8 mL), twice daily via intramuscular injection, with a treatment duration of ≤4 days and a follow-up period of 7 days. The treatment efficacy and safety were compared between the two groups.@*RESULTS@#The total effective rate on the 3rd day after treatment in the test group was significantly higher than that in the control group (P<0.05), while there was no significant difference in the total effective rate on the 5th day between the two groups (P>0.05). The rates of fever relief, cough relief, and lung rale relief in the test group on the 3rd day after treatment were higher than those in the control group (P<0.05). The cough relief rate on the 5th day after treatment in the test group was higher than that in the control group (P<0.05), while there was no significant difference in the fever relief rate and lung rale relief rate between the two groups (P>0.05). The cough relief time, daily cough relief time, and nocturnal cough relief time in the test group were significantly shorter than those in the control group (P<0.05), while there were no significant differences in the fever duration and lung rale relief time between the two groups (P>0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05).@*CONCLUSIONS@#The overall efficacy of combined routine treatment with intramuscular injection of Xiyanping injection in the treatment of acute bronchitis in children is superior to that of routine treatment alone, without an increase in the incidence of adverse reactions.

The affinity maturation, characteristics and application of HIV-1 broadly neutralizing antibodies / 中华预防医学杂志

Hundreds of broadly neutralizing antibodies(bNAbs) were successfully isolated from long-term nonprogression(LTNP) of human immunodeficiency virus type 1(HIV-1) infected individuals. Some bNAbs were illustrated could reduce the viral load and the risk of HIV-1 infection. Today, HIV-1 bNAbs are at the center of vaccine development and passive immunization treatment. Usually, the activity of neutralizing antibodies depends on the epitope. The affinity of neutralizing antibodies also plays a vital role in its inhibitory effect. Multiple affinity maturation in vivo actually provides the broad and potent neutralizing activity of HIV-1 bNAbs. When high affinity HIV-1 bNAbs applied in clinic, it can help immune system to remove virus with lower dosage and fewer side effect. While affinity maturation, HIV-1 bNAbs shows unique characteristics, such as extensive of somatic hypermutation(SHM), in-frame insertion and deletion and long CDR 3 region of heavy chain. The key points in the progress that HIV-1 bNAbs affinity maturation will help us understand the relationship between antibodies neutralizing capability and its characteristics.It also potentially provide a reference to design effective HIV-1 immunogen.

Predictive value of prostate biopsy results based on predictive model established by the PI-RADS version 2 / 中华泌尿外科杂志

Objective To explore a predictive nomogram for the result of prostate biopsy based on Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) combined with prostate specific antigen (PSA) and its related parameters,and to assess its ability to diagnose prostate cancer by internal validation.Methods We retrospectively analyzed the clinical data of 509 patients who underwent transrectal prostate biopsy guided by ultrasound during the period from January 2014 to December 2018 in the Department of Urology,First Affiliated Hospital of Xiamen University.In 509 cases,the mean age was (68.1 ± 7.2) years.The mean prostate volume (PV) was (55.8 ± 30.7) ml.The mean tPSA value was (19.86 ± 18.94) ng/ml.The mean value of fPSA was (2.63 ± 3.60) ng/ml and the mean f/tPSA was 0.14 ± 0.08.The mean PSAD was (0.46 ±0.52) ng/ml2.Based on the PI-RADS v2,score 1 point have 37 cases,score 2 point have 131 cases,score 3 point have 152 cases,score 4 point have 102 cases,score 5 point have 87 cases.Of these patients,we randomly selected 80％ (407 cases) as development group,and the other 20％ (102 cases) as validation group.Univariate and multivariate logistic regression analysis of the development group was performed to identify the independent influence factors that can predict prostate cancer (PCa),thereby establishing a predictive model for the result of prostate biopsy.In the development group,validation group and tPSA was between 4.1-20.0 ng/ml,the model was evaluated by analyzing the receiver operating characteristic (ROC) curve,calibration curve and decision curve,and compared to PSA,fPSA,f/tPSA,PSAD,PI-RADS v2.Results Among the 509 patients enrolled in the study,the detection rate of PCa was 43.0％ (219/509).In the development group,the logistic regression analysis demonstrated that patient age (OR =1.113),f/tPSA (OR =0.004),PV (OR =0.986),PSAD (OR =11.023),digital rectal examination (DRE) texture (OR =2.295),transabdominal ultrasound (TAUS) with or without hypoechoic (OR =2.089),and PI-RADS v2 (OR =1.920) were independent factors for PCa (P ＜0.05).The nomogram based on all variables was established.In the development group,the area under the curve (AUC) of the model (0.883) was greater than those of tPSA (0.686),fPSA (0.593),f/tPSA (0.626),PSAD (0.777),PI-RADS v2 (0.761).In the validation group,the area under the curve of the model (0.839) was greater than those of tPSA (0.758),fPSA (0.666),f/tPSA (0.648),PSAD (0.832),PI-RADS v2 (0.803).In patients whose tPSA was between 4.1-20.0 ng/ml,the area under the curve of the model (0.801) was greater than those of tPSA (0.570),fPSA (0.426),f/tPSA (0.657),PSAD (0.707),PI-RADS v2 (0.701).The calibration curve of the nomogram indicated that the prediction curve was basically fitted to the standard curve,and the Hosmer-Lemeshow showed thatx2 =5.434,P =0.710,both suggested that the prediction model had better calibration ability.The decision curve showed that the model based on PI-RADS v2 had high clinical application value.Conclusions The nomogram based on PI-RADS v2 had a high predictive value for prostate cancer and could significantly improve the diagnostic performance.It had better diagnostic value than PSA and its related parameters.It also provided important guidance for the prostate cancer on clinical treatment of patients to some extent.

Predictive value of prostate biopsy results based on predictive model established by the PI-RADS version 2 / 中华泌尿外科杂志

Objective@#To explore a predictive nomogram for the result of prostate biopsy based on Prostate Imaging Reporting and Data System version 2(PI-RADS v2)combined with prostate specific antigen (PSA) and its related parameters, and to assess its ability to diagnose prostate cancer by internal validation.@*Methods@#We retrospectively analyzed the clinical data of 509 patients who underwent transrectal prostate biopsy guided by ultrasound during the period from January 2014 to December 2018 in the Department of Urology, First Affiliated Hospital of Xiamen University. In 509 cases, the mean age was (68.1±7.2) years. The mean prostate volume(PV) was (55.8±30.7) ml. The mean tPSA value was (19.86±18.94) ng/ml. The mean value of fPSA was (2.63±3.60) ng/ml and the mean f/tPSA was 0.14±0.08. The mean PSAD was (0.46±0.52) ng/ml2. Based on the PI-RADS v2, score 1 point have 37 cases, score 2 point have 131 cases, score 3 point have 152 cases, score 4 point have 102 cases, score 5 point have 87 cases. Of these patients, we randomly selected 80% (407 cases) as development group, and the other 20% (102 cases) as validation group. Univariate and multivariate logistic regression analysis of the development group was performed to identify the independent influence factors that can predict prostate cancer (PCa), thereby establishing a predictive model for the result of prostate biopsy. In the development group, validation group and tPSA was between 4.1-20.0 ng/ml, the model was evaluated by analyzing the receiver operating characteristic (ROC) curve, calibration curve and decision curve, and compared to PSA, fPSA, f/tPSA, PSAD, PI-RADS v2.@*Results@#Among the 509 patients enrolled in the study, the detection rate of PCa was 43.0% (219/509). In the development group, the logistic regression analysis demonstrated that patient age (OR=1.113), f/tPSA (OR=0.004), PV (OR=0.986), PSAD (OR=11.023), digital rectal examination (DRE) texture (OR=2.295), transabdominal ultrasound (TAUS) with or without hypoechoic (OR=2.089), and PI-RADS v2 (OR=1.920) were independent factors for PCa (P<0.05). The nomogram based on all variables was established. In the development group, the area under the curve (AUC) of the model (0.883) was greater than those of tPSA (0.686), fPSA (0.593), f/tPSA (0.626), PSAD (0.777), PI-RADS v2 (0.761). In the validation group, the area under the curve of the model (0.839) was greater than those of tPSA (0.758), fPSA (0.666), f/tPSA (0.648), PSAD (0.832), PI-RADS v2 (0.803). In patients whose tPSA was between 4.1-20.0 ng/ml, the area under the curve of the model (0.801) was greater than those of tPSA (0.570), fPSA (0.426), f/tPSA (0.657), PSAD (0.707), PI-RADS v2 (0.701). The calibration curve of the nomogram indicated that the prediction curve was basically fitted to the standard curve, and the Hosmer-Lemeshow showed thatχ2=5.434, P=0.710, both suggested that the prediction model had better calibration ability. The decision curve showed that the model based on PI-RADS v2 had high clinical application value.@*Conclusions@#The nomogram based on PI-RADS v2 had a high predictive value for prostate cancer and could significantly improve the diagnostic performance. It had better diagnostic value than PSA and its related parameters. It also provided important guidance for the prostate cancer on clinical treatment of patients to some extent.

Study of removing the Medpor and transplanting an expander at the same operative stage to repair the Medpor exposure after ear reconstruction / 中华整形外科杂志

Objective@#To explore the clinical effect by using expander implantation immediately to repair the Medpor exposure after ear reconstruction.@*Methods@#From May 2013 to February 2017, 5 patients were treated with ear reconstructive surgery by Medpor implantation. The previous methods contained not only the auricular posterior fascia flap but also skin grafting. Exposed parts were the upper part of the helix and the wounds were dry without purulent secretions. Bacterial culture did not show bacterial growth. Surgical procedure was to remove the Medpor implant and implant a 50 ml kidney expander. When the wound was healed, we started to inject normal saline into the expander. About 3 months later the total volume of normal saline in the expanders were 80-100 ml.Then we could begin the second operation. We removed the expander and harvested the right side of the 7th and 8th rib cartilage, which were carved into the ear cartilage framework and transplanted into the expansion area. The drainage tube, negative pressure and cotton pad appropriate pressure bandage were needed. 6 days later we removed drainage tube.10 days later we removed the suture.@*Results@#The reconstructed external ear shape in five cases were good. No infection occurred. With 6-20 months of follow-up using telephone and WeChat, no obvious deformation of the shape or cartilage exposure occurred. The five patients did not come back to do the third stage operation for financial considerations. They all left their hometown to work out to reduce economic pressure.@*Conclusions@#In the case of ear reconstruction for Medpor prosthesis exposure, if the wounds were not infected, removing the Medpor and transplanting an expander at the same operative stage can achieve a good therapeutic effect.

Application of controllable hair density of eyebrow reconstruction with the treatment of scar baldness during the same operation stage / 中华医学美学美容杂志

Objective To explore a method of eyebrow reconstruction which can control eyebrows,and to repair scar baldness in the same operation stage.Methods Operations were performed in two stages.In the first stage,an expander was placed under the scalp at the same side of the defect eyebrow through the direction of the superficial temporal artery.Other expanders were placed around the scar baldness.After the incision healed,water was injected into the expander.During the expansion,the scalp hair density was approaching the uninjured eyebrow side.Then the second stage operation was prepared:an island flap with superficial temporal artery as axial artery was harvested and the expander was extracted.The subcutaneous tunnel was made in the temporal region of the eyebrow defect side.The expanded superficial temporal artery island scalp flap was passed through the tunnel and transferred to the defect eyebrow area to repair the eyebrow.After incising the scar baldness,the left expanded scalp flaps were transferred to cover the wound.Results 12 patients underwent this method of eyebrow reconstruction with scar baldness,all island scalp flaps survived,with no case of flap necrosis.After 6-24 months of follow-up,the hair density of the reconstructed eyebrows was very close to that of the uninjured side,without excessive thickening or excessive rarefaction.The scalp scars were small and can be shaded by the hair.All patients were satisfied with the operation.Conclusions The method of controllable hair density of eyebrow reconstruction with the treatment of scar baldness has good effects on reconstructing eyebrow defect and scar baldness.It is simple,economic and suitable for further application.

Preventive application of antibiotic in plastic surgery / 中华医学美学美容杂志

Objective To investigate the reasonable proposal of prophylactic antibiotics use in plastic surgery with type Ⅰ incision.Methods The data of 748 patients with plastic surgery in our hospital were collected and the operation number was 770.Using a retrospective case-control study,we analysed the clinical effect of different administration methods.Results Clinical effects were compared among the multiple days medication group,normative administration group and no medication groups,and there was no significant difference in the prevention of postoperative infection results.Conclusions Plastic surgery with type Ⅰ incision does not need the prophylactic application of antibiotics.In special circumstances we should take medicine in strict accordance with the Guiding Principles for Clinical Application of Antibiotics.

Ear reconstruction using autologous rib cartilage ear framework by multi-layer spliced sculpture in microtia patients / 中华医学美学美容杂志

Objective To explore ear reconstruction using autologous rib cartilage ear framework by multi-layer spliced sculpture in microtia patients.Methods From Feb 2010 to May 2011,29 microtia patients were subjected to ear reconstruction using autologous rib cartilage ear framwork by four-layer spliced sculpture.Results In one operation 29 patients achieved 2 cm transverse height of reconstructed ears which were basically coincidence with the normal side.Patents and their families were all satisfied with the results.Follow-up of 3-12 months showed that only 1 case reconstructed-ear height was significantly lower transverse process.Owing to sleeping position,the patient did not protect the reconstructed ear,leading to frequent reconstructed-ear pressure.Conclusions The method of multi-layer spliced sculpture autologous rib cartilage ear reconstruction has good clinical effect.It can make reconstructed ear reach nomal transverse height and avoid the third rib cartilage transplant operation to continue increasing the transvers height.

Otoplasty of slited cartilage to correct flaring ear / 中华医学美学美容杂志

Objective To study a new method of correcting flaring ear. Methods Auricular cartilage was slited from posterior auricula. On Gibson's principle of cartilage distortion antero-lateral cartilage membrane was scarified in order of the involute interpolation of anthelix and cartilage membrance was ground. Then the cartilage outside the slited line was put behind the cartilage inside the slited line. Finally,cartilage was operated with Mustarde's mattres suture. Results 12 patients with flaring ear ( 14 ears) were corrected with this operating method and appearance of corrected ears were very good after operation. Following up for 6-18 months, no one recurred. Conclusion Otoplasty of slited cartilage is an effective method of correcting flaring ear.