In recent years,the tumor microenvironment(TME)has garnered significant attention from scientists.It is a com-plex system composed of tumor cells,cancer-associated fibroblasts(CAFs),immune cells,blood vessels,extracellular matrix,sur-rounding supportive tissues and their metabolic environment.Two fundamental characteristics of this system are immune escape and metabolic changes(the shift from aerobic to anaerobic metabolism of glucose,leading to lactate production).Although lactate has tra-ditionally been considered a metabolic"waste"product in the TME,it is now widely recognized that the increase in lactate and the acidification of the tumor microenvironment play key roles in tumor development and progression,including immune escape,tissue in-vasion/tumor metastasis,angiogenesis and tumor drug resistance.Therefore,studying the regulatory mechanisms of lactate metabo-lism,immune suppression,angiogenesis,and tumor drug resistance in the TME can provide a theoretical basis and practical evidence for new therapeutic strategies targeting the TME.

Objective To investigate the characteristics and clinicopathology of v-raf murine sarcoma viral oncogene homolog Bl(BRAF)V600E mutations in papillary thyroid carcinoma(PTC)in Air Force flight personnel.Methods Data of cases and test results of BRAF V600E mutation were collected from Air Force aviators pathologically diagnosed with PTC.A univariate analysis of the relationship between BRAF V600E mutations and clinicopathologic features was performed.Results The overall rate of BRAF V600E mutations among 55 PTC flight crew members was 70.91％.The univariate analysis showed that the number of lymph node metastases in the BRAF V600E mutated group was larger than in the BRAF V600E unmutated group,and the proportion of BRAF V600E mutations in flight crews at intermediate risk of recurrence was higher than that in those at low risk of recurrence(P＜0.05).The presence or absence of BRAF V600E mutations did not affect the results of medical evaluation of PTC in flight personnel.Conclusion The rate of PTC BRAF V600E mutations in Air Force flight crews is similar to that of the general Chinese population.BRAF V600E mutations are associated with an increased number of lymph node metastases and risk of recurrence,and follow-up is recommended for flight personnel with PTC,especially those with BRAF V600E mutations.

In acute lung injury, two subsets of lung macrophages exist in the alveoli: tissue-resident alveolar macrophages (AMs) and monocyte-derived alveolar macrophages (MDMs).However, it is unclear whether these 2 subsets of macrophages have different functions and characteristics during the recovery phase. RNA-sequencing of AMs and MDMs from the recovery period of LPS-induced lung injury mice revealed their differences in proliferation, cell death, phagocytosis, inflammation and tissue repair. Using flow cytometry, we found that AMs showed a higher ability to proliferate, whereas MDMs expressed a larger amount of cell death. We also compared the ability of phagocytosing apoptotic cells and activating adaptive immunity and found that AMs have a stronger ability to phagocytose, while MDMs are the cells that activate lymphocytes during the resolving phase. By testing surface markers, we found that MDMs were more prone to the M1 phenotype, but expressed a higher level of pro-repairing genes. Finally, analysis of a publicly available set of single-cell RNA-sequencing data on bronchoalveolar lavage cells from patients with SARS-CoV-2 infection validated the double-sided role of MDMs. Blockade of inflammatory MDM recruitment using CCR2 −/− mice effectively attenuates lung injury. Therefore, AMs and MDMs exhibited large differences during recovery. AMs are long-lived M2-like tissue-resident macrophages that have a strong ability to proliferate and phagocytose. MDMs are a paradoxical group of macrophages that promote the repair of tissue damage despite being strongly pro-inflammatory early in infection, and they may undergo cell death as inflammation fades. Preventing the massive recruitment of inflammatory MDMs or promoting their transition to pro-repairing phenotype may be a new direction for the treatment of acute lung injury.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.

Objective To modify the mouse model of orthotopic left lung transplantation from different perspectives, aiming to establish a simpler, faster and stabler mouse model of lung transplantation. Methods Based on preliminary modified rat model of orthotopic left lung transplantation established by our team, varying extent of modifications were made regarding the tracheal intubation, cannula preparation and anastomosis procedures of orthotopic left lung transplantation in the recipient mice. Orthotopic left lung transplantation in 40 mice were performed by an operator with microsurgical experience. The dissection of the recipient's hilar structure was carried out at the plane of the hilar clamp model within the reverse-view, and the three branches (left main bronchus, pulmonary artery and pulmonary vein) of the pulmonary hilum were anastomosed in turn by the "pendulum" anastomosis method. The operation time of each procedure was recorded. The recipient mice were sacrificed at postoperative 2 weeks, and the incidence of postoperative complications was recorded. Results Lung transplantation was successfully completed in 40 mice, with no bronchial and vascular tearing or twisting, and no bleeding at the anastomosis site. The overall cardiopulmonary procurement time was (10.7±1.5) min, cannula preparation time was (16.2±1.5) min, cold ischemia time was (25.1±2.4) min, warm ischemia time was (19.4±1.6) min, and the total operation time was (57.2±2.9) min, respectively. During the follow-up from 6 to 14 days after surgery, one recipient mouse died of pleural effusion, probably caused by infection. No pneumothorax, thrombosis or atelectasis was found in the remaining recipient mice during postoperative follow-up. Conclusions The modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane possesses multiple advantages of short operation time, high success rate and few complications, which is expected to become an alternative model of studying pathological changes after lung transplantation and worthy of further application.

Objective:To investigate the feasibility, efficacy, and safety of CT- and bronchoscopy-guided 125I seed implantation in the treatment of central lung cancer complicated with atelectasis. Methods:Retrospective analysis was conducted on twenty-nine patients who were treated from May 2016 to Oct 2019 in the Second Hospital of Tianjin Medical University for central non-small-cell lung carcinoma complicated with pulmonary atelectasis that was inoperable due to medical reasons. 125I seeds were implanted into the trachea under the guidance of bronchoscopy first.The 125I seeds were then implanted into the hilum of the lungs by percutaneous puncture under the guidance of the CT and template.The seed activity was 18.5-29.6 MBq, and the prescription dose was 120 Gy.TPS planning and quality verification were performed before and after the operations.The rate of atelectasis recanalization, the satisfactory rate of dose verification, the improvement of dyspnea index, the survival time, and the adverse events during and after operation were observed. Results:All 29 patients with lung cancer complicated with atelectasis successfully completed the seed implantation, and the satisfactory rate of quality verification was 93.1%.The rate of atelectasis recanalization at 2, 6, 12, 18, and 24 months was 93.1%, 89.7%, 78.6%, 76.2%, and 60%, respectively.Their dyspnea and anoxia symptoms were significantly relieved in 5-28 months after treatment.The results showed that the patients′ dyspnea index was 2.8-0.8 before treatment and 1.4-0.9 after treatment.The median follow-up period was 20 months and median survival was 21 months.Adverse events associated with the radiation therapy included pneumothorax, hemoptysis, cough, fever, and particle displacement.No level-3 or more serious adverse events occurred.Conclusions:The CT- and bronchoscopy-guided 125I seed implantation is a safe and effective therapy option for the treatment of central non-small-cell lung carcinoma associated with atelectasis.It contributes to a high rate of local recanalization, and can rapidly improve clinical conditions and quality of life of the patients with few adverse reactions.

Three-dimensional (3D) printing technique has been improving the industrial process from uniform pipeline production procedure in manufacture into individualized production with distributed network. 3D printing technique also provokes these changes in the field of medicine, especially in orthopedics, stomatology and radiology. The role of 3D printing technique has been increasingly highlighted in tumor radiotherapy. Current studies and application mainly focus on personalized tissue compensato (bolus), brachytherapy (high-dose post-loading and particle implantation therapy), 3D printing personalized phantom and individualized fixtures, etc. In this article, research progresses on the application of 3D printing technique in radiotherapy at home and abroad were reviewed.

Objective:To observe the efficacy and safety of the combination of agomelatine and low-dose olanzapine (AO) in the treatment of postprandial distress syndrome (PDS) with depression, anxiety and sleep disorders.Methods:From April 2019 to September 2020, PDS patients with depression, anxiety and sleep disorders in Tianjin Medical University General Hospital were selected and divided into AO group and flupentixol-melitracen (FM) group. Patients of the AO group were given oral agomelatine 25 mg and AO 1.70 mg (both once per day), and the patients of FM group were given oral FM 10.5 mg (once per day), and all patients took itopride 50 mg (three times per day) at the same time. The total treatment course was eight weeks. Nepean dyspepsia index-symptom (NDIS), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Pittsburgh sleep quality index (PSQI) were used to evaluate the gastrointestinal symptoms, depression, anxiety and sleep disorders before treatment and two, four and eight weeks after treatment, respectively. The efficacy was evaluated according to the changes of scores of gastrointestinal symptoms before and after treatment. The adverse effects after medication were recorded. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 184 PDS patients with depression, anxiety and sleep disorders were enrolled, including 98 patients in AO group and 86 patients in FM group. At two, four and eight weeks after treatment, NDIS, PHQ-9, GAD-7 and PSQI scores of AO group and FM group were all lower than those of each group before treatment (AO group: 13.73±0.53, 10.13±0.44 and 7.87±0.31 vs. 27.08±0.84; 6.04±0.35, 4.70±0.31 and 3.81±0.22 vs. 10.04±0.50; 6.36±0.30, 5.29±0.28 and 4.21±0.19 vs. 10.71±0.51; 6.64±0.37, 5.27±0.35 and 4.09±0.30 vs. 11.14±0.42; FM group: 15.33±0.58, 11.58±0.50 and 9.80±0.35 vs. 25.10±0.79; 6.79±0.35, 5.71±0.32 and 4.86±0.30 vs. 9.11±0.46; 7.27±0.31, 6.51±0.32 and 5.21±0.27 vs. 9.79±0.44; 8.01±0.33, 6.76±0.32 and 5.78±0.32 vs. 10.44±0.32), and the differences were statistically significant (AO group: tNDIS=13.470, 17.930 and 21.530, tPHQ-9=6.488, 8.991 and 11.300, tGAD-7=7.361, 9.315 and 11.031, tPSQI=7.088, 9.736 and 12.550. FM group: tNDIS=9.921, 14.400 and 17.640, tPHQ-9=4.032, 6.106 and 7.781, tGAD-7=4.638, 5.993 and 8.840, tPSQI=5.289, 8.199 and 10.310, all P<0.05). At two, four and eight weeks after treatment, NDIS, GAD-7 and PSQI scores of AO group were all lower than those of the FM group during the same period (NDIS: 13.73±0.53 vs. 15.33±0.58, 10.13±0.44 vs. 11.58±0.50, 7.87±0.31 vs. 9.80±0.35; GAD-7: 6.36±0.30 vs. 7.27±0.31, 5.29±0.28 vs. 6.51±0.32, 4.21±0.19 vs. 5.21±0.27; PSQI: 6.64±0.37 vs. 8.01±0.33, 5.27±0.35 vs. 6.76±0.32, 4.09±0.30 vs. 5.78±0.32), and the differences were statistically significant ( tNDIS=2.018, 2.225 and 4.156, tGAD-7=2.097, 2.869 and 2.536, tPSQI=1.951, 2.359 and 3.099, all P<0.05). At eight weeks after treatment, the total effective rate of the AO group was higher than that of the FM group (94.9%, 93/98 vs. 84.9%, 73/86), and the difference was statistically significant ( χ2=5.205, P=0.026). The incidence of adverse reactions of constipation and somnolence of the AO group were both lower than those of the FM group (2.0%, 2/98 vs. 9.3%, 8/86 and 1.0%, 1/98 vs. 8.1%, 7/86, respectively), and the differences were statistically significant ( χ2=4.699 and 5.582, P=0.047 and 0.027). Conclusion:AO may be a treatment option for PDS with depression, anxiety and sleep disorders.

Objective:To analyze the clinical efficacy and safety of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma (HCC).Methods:Ninety-four cases with mid-and advanced-stage HCC who received camrelizumab combined with apatinib as second-line treatment were enrolled. Routine blood test, blood biochemical indexes, tumor stage, tumor imaging characteristics, previous treatment strategies and other clinical data before treatment were documented. Imaging examination follow-up results and adverse reactions during treatment were followed up until the end of follow-up or loss of follow-up or death. Kaplan-Meier method was used to analyze the clinical efficacy.Results:As of the last follow-up, 94 cases with mid-and advanced-stage HCC had received camrelizumab combined with apatinib as second-line treatment. Among them, 15 cases were lost to follow-up, 31 cases died, and 48 cases survived. The overall remission rate was 31.9%. The overall disease control rate was 71.3%. The median time to disease-free progression was 6.6 months. The median time to disease progression was not yet available. The 1-year cumulative survival rate was 62.3%. Grade 3 and above adverse reactions mainly included were thrombocytopenia (7.4%), abdominal pain (4.3%), active hepatitis (4.3%), leukopenia (4.3%), diarrhea (3.2%), hand-foot syndrome (3.2%). All adverse reactions were effectively controlled.Conclusion:Camrelizumab combined with apatinib can effectively prolong the survival period of patients with mid-and advanced-stage HCC, and it is well tolerated.