Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

[Annual review of bronchiectasis research in 2023].

This review focuses on the latest advances in bronchiectasis from October 1st, 2022 to September 30th, 2023, including the etiology, diagnosis, treatment, comorbidities, and management of bronchiectasis in order to provide a reference in clinical diagnosis and treatment, and future research of bronchiectasis for domestic peers.

[Efficacy of 0.05% cyclosporine A combined with vitamin A palmitate in the treatment of meibomian gland dysfunction-related dry eye].

Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer Ⅰ test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.

Differentiation of giant cell tumours of bone, primary aneurysmal bone cysts, and aneurysmal bone cysts secondary to giant cell tumour of bone: using whole-tumour CT texture analysis parameters as quantitative biomarkers.

AIM: To determine whether computed tomography (CT) texture analysis parameters can be used as quantitative biomarkers to help differentiate giant cell tumour of bones (GCTs), primary aneurysmal bone cysts (PABCs), and aneurysmal bone cysts (ABCs) secondary to giant cell tumours of bone (GABCs). MATERIALS AND METHODS: One hundred and seven patients with 63 GCTs, 31 PABCs, and 13 GABCs were analysed retrospectively. All patients underwent preoperative CT. Two radiologists independently evaluated the qualitative features of the CT images and extracted texture parameters. Patient demographics, qualitative features, and texture parameters among GCTs, PABCs, and GABCs were compared statistically. Differences in these parameters between ABCs and GCTs were also assessed. ROC curves were obtained to determine optimal parameter values. RESULTS: The best preoperative CT parameters to differentiate GCTs, PABCs, and GABCs included one qualitative feature (location around the knee) and four texture parameters (95th percentile, maximum intensity, skewness, and kurtosis). Age and three texture parameters (5th percentile, inhomogeneity, and kurtosis) enabled statistically significant differentiation between GCTs and ABCs. Combination of the above four parameters generated the largest area under the ROC curve (AUC) for the differentiation of GCTs and ABCs. CONCLUSION: CT texture analysis parameters can be used as quantitative biomarkers for preoperative differentiation among GCTs, PABCs, and GABCs.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

[Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study].

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

[Endoscopic ultrasonographic features of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors and their correlation with progression and pathological risk grade of the lesions].

Objective: To investigate the endoscopic ultrasonographic (EUS) characteristics of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors (GIST) and their correlation with biological behaviors and pathological risk grade of the tumors. Methods: Retrospective cohort study. The EUS findings, follow-up review, surgical treatment and pathological data of patients with suspected GIST at the Gastrointestinal Endoscopy Center of Peking University People's Hospital from January 2013 to April 2021 were collected. All samples were divided into follow-up group and treatment group based on the pathological condition and the patient's treatment intention. According to whether or not the tumor was enlarged in EUS, the follow-up group was divided into non-enlarged group and enlarged group. Paired T-test was used to compare the lesion size before and after follow-up, and logistic regression was used to analyze the risk factors of tumor enlargement. According to the treatment methods, the treatment group was further divided into endoscopic treatment group and surgical treatment group. According to the pathological results and risk grade, the treatment group was further divided into the low-risk group and the medium-risk group. The risk factors of pathological malignant risk were analyzed by logistic regression, and the tumor diameter of patients with moderate or above pathological risk was predicted by receiver operation characteristic (ROC) curve. The relationship between the findings of EUS and the progression and pathological risk of GIST were also explored. Results: Seventy-three cases including 23 males and 50 females, with an age of 58 (30-88) years, were included in the follow-up group, with a mean lesion diameter of (1.21±0.49) cm before follow-up, median follow-up interval of 33.8 months, and a lesion diameter of (1.18±0.49) cm after follow-up. There was no significant difference (all P>0.05) in lesion diameter between before and after follow-up. There was no significant difference (all P>0.05) between tumor enlargement group (18 cases, 24.7%) and non-enlargement group (55 cases, 75.3%). One hundred and thirty-eight cases, including 52 males and 86 females, with an age of 60 (19-84) years, were enrolled in the treatment group, with a mean EUS estimated diameter of (2.55±1.35) cm and pathological diameters of (3.43±2.42) cm. Ninety-five (68.8%) of these cases were pathologically confirmed as GIST while 43 cases were diagnosed as other tumor types, including 37 benign tumors and 6 malignant tumors. In multifactorial logistic regression analysis, only the increase of tumor diameter [OR (95%CI): 1.800 (1.172-2.766), P=0.007] was a risk factor for pathological intermediate or higher risk. The optimal tumor diameter for predicting pathological intermediate or higher risk using ROC curve analysis was 2.75 cm, with a sensitivity 71.4%, specificity 79.0%, Youden index 0.5 and area under ROC curve 0.807 (95%CI: 0.703-0.909). Conclusions: EUS is essential for assessing the risk of progression and malignancy of submucosal lesions of upper digestive tract suspected GIST. For lesions of small diameter, the interval of follow-up shall be relatively extended while the indication of treatment could be partially waived.

[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

[Application value of questionnaires in the screening obstructive sleep apnea syndrome in pregnancy across trimesters].

Objective: To evaluate the clinical utility value of questionnaires of Berlin, STOP, STOP-Bang (SBQ), Epworth Sleepiness Scale (ESS) in screening obstructive sleep apnea syndrome (OSAS) in pregnant women of different trimesters. Methods: Consecutive pregnant women at high risk for OSAS were enrolled from January, 2021 to April, 2022 at the obstetric clinic of Peking University People's Hospital. They completed questionnaires of Berlin, STOP, SBQ, ESS and also underwent an overnight polysomnography (PSG). To evaluate the accuracy of questionnaires of Berlin, STOP, SBQ, ESS, sensitivity, specificity, positive predictive values, negative predictive values and the area under the receiver operating characteristics (ROC) curve of these questionnaires in pregnancy across trimesters (Pregnancy 1-15 weeks was the first stage, pregnancy 16-27 weeks was the second stage, and pregnancy 28-40 weeks was the third stage) were calculated. Results: A total of 100 pregnant women [(34.5±4.3) years old (26-46 years old)] were included in this study, including 20, 35 and 45 pregnant women in the first, second and third trimester of pregnancy, respectively. Based on PSG results, 45 (45%) of 100 pregnant women were diagnosed with OSAS. The overall predictive values of the four questionnaires were not good, area under[AUC(95%CI)] the ROC curve ESS, Berlin questionnaire STOP and SBQ were 0.54(0.43, 0.66), 0.59 (0.47, 0.70), 0.62(0.51, 0.73) and 0.61 (0.49, 0.72), respectively, sensitivity was 35.6%, 65.9%, 48.9%, 28.9%, specificity was 71.7%, 52.5%, 73.6%, 92.5%. When categorized according to trimesters, the predicted values of the four questionnaires increased in the first trimester, the AUC (95%CI) of STOP questionnaire was 0.81 (0.61, 1.00), sensitivity was 75.0%, specificity was 87.5%. Conclusion: The overall predictive power of the four screening questionnaires is limited in pregnant women. But predictive value of STOP questionnaire is acceptable in the first trimester.

[Relationships between hypertensive disorders in pregnancy and obstructive sleep apnea syndrome].

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m2) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.

[The prospect and challenge of liquid biopsy in the diagnosis and treatment of chest malignancy].

In recent years, the incidence of chest malignant tumors in China has increased year by year, which has seriously threatened the health problems of people. Among them, early screening and intervention of patients with chest malignancies is the key to cancer prevention. Early detection, early diagnosis, and early treatment as the "three early prevention" of clinical practice are conducive to improve the survival rate of tumor patients. As a non-invasive and real-time reflection of tumor status, liquid biopsy has gradually received attention in clinical diagnosis and treatment. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes as liquid biopsy "Three carriages" are not only widely used in the diagnosis, monitoring and prognostic evaluation of chest malignancies, but also face many unknown challenges. In this article, the application of liquid biopsy in chest malignancies in recent years is elaborated in detail, which provides a reference for the formulation of clinical tumor prevention and diagnosis and treatment strategies.

[Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection].

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

[Effects of electric welding on hearing loss and respiratory damage].

Objective: To investigate the occupational health status of electric welding workers and explore the effects of electric welding on hearing loss and respiratory damage. Methods: From August to December 2021, the cluster sampling method was used to select workers from an automobile manufacturer in Guangzhou City as research subjects: 636 welding workers in the welding workshop as the welding group, 757 assembly workers in the engine workshop and the final assembly workshop exposed to pure noise as the assembly group. Occupational disease hazard factors were detected for welding positions and assembly positions, and occupational health examination was carried out for research subjects. The occupational health status, the trends of hearing loss and respiratory abnormalities with working age were compared and analyzed between the two groups. Binary logistic regression was used to analyze the association between hearing loss and respiratory abnormalities in welding workers. Results: The excess rates of welding fumes, manganese and its compounds in the welding position were both 9.68% (3/31). Its noise exposure intensity [ (85.36±2.68) dB (A) ] and excess rate [48.39% (15/31) ] were not significantly different from those in the assembly position [ (84.86±3.28) dB (A) and 43.24% (16/37) ] (P>0.05). The results of the occupational health examination showed that the detection rates of hearing loss, digital radiography (DR) chest X-ray abnormality, alanine aminotransferase abnormality, deazelaic aminotransferase abnormality and white blood cell count abnormality of workers in the welding group were higher than those in the assembly group (P<0.05). The detection rates of hearing loss, DR chest X-ray abnormality, pulmonary ventilation abnormality in the welding group and the detection rate of hearing loss in the assembly group increased with the working age of the workers (P<0.05). The hearing loss detection rate and DR chest X-ray abnormality detection rate of the workers with ≥9 years working age in the welding group were both higher than those in the assembly group workers with same working age (P<0.05). The binary logistic regression analysis showed that abnormal pulmonary ventilation and abnormal DR chest X-ray were the risk factors for hearing loss in welding workers (OR=10.83, 95%CI: 7.31-16.06; OR=16.59, 95%CI: 5.72-48.10; P<0.05) . Conclusion: Hearing loss and respiratory damage are prominent problems among welding workers, and the detection rates of abnormality increase with the working age of the workers. Hearing loss in welding workers is associated with abnormal pulmonary ventilation and abnormal DR chest X-ray.

PHGDH promotes the proliferation and differentiation of primary chicken myoblasts.

1. Chicken primary myoblasts (CPMs) are precursors that form muscle fibres. The proliferation and differentiation of CPMs is an essential stage in muscle development. Previous RNA-seq analysis showed that phosphoglycerate dehydrogenase (PHGDH) is a differentially expressed gene in chicken muscle tissue at different growth stages. Therefore, the following study explored the effect of PHGDH on the proliferation and differentiation of CPMs.2. The effect on the proliferation of CPMs by RT-qPCR, CCK-8, and EdU assays after the overexpression and knockdown of PHGDH was evaluated. RT-qPCR, western blotting, and indirect immunofluorescence were used to detect the effect of PHGDH on the differentiation of the CPMs. The expression was observed at different time points for differentiation induced by the CPMs.3. The results showed that PHGDH significantly promoted proliferation and differentiation in CPMs. The results showed that overexpression of PHGDH significantly upregulated CPM proliferation, while knockdown had the opposite effect. Marker genes showed that overexpression of PHGDH significantly upregulated the expression of P21, MYOG and MYOD genes, significantly downregulated the expression of the MSTN gene and promoted the expression of the MYHC protein. In contrast, PHGDH knockdown had the opposite effect.4. Desmin immunofluorescence analysis of myotube differentiation in primary myoblasts showed that overexpression of PHGDH significantly increased the area of myotube differentiation and promoted the proliferation and differentiation of myoblasts. Knockdown of PHGDH had the opposite effect.5. In summary, PHGDH was shown to play a positive role in regulating myoblast proliferation and differentiation. This provides a theoretical basis for further analysis of the regulatory mechanism of the PHGDH gene in chicken muscle development and for improving poultry production.

The potential effect of microbiota in predicting the freshness of chilled chicken.

1. The goals of this study were to analyse the changes in microbiota composition of chilled chicken during storage and identify microbial biomarkers related to meat freshness.2. The study used 16S rDNA sequencing to track the microbiota shift in chilled chicken during storage. Associations between microbiota composition and storage time were analysed and microbial biomarkers were identified.3. The results showed that microbial diversity of chilled chicken decreased with the storage time. A total of 27 and 24 microbial biomarkers were identified by using orthogonal partial least squares (OPLS) and the random forest regression approach, respectively. The receiver operating characteristic (ROC) curve analysis indicated that the OPLS regression approach had better performance in identifying freshness-related biomarkers. The multiple stepwise regression analysis identified four key microbial biomarkers, including Streptococcus, Carnobacterium, Serratia and Photobacterium genera and constructed a predictive model.4. The study provided microbial biomarkers and a model related to the freshness of chilled chicken. These findings provide a basis for developing detection methods of the freshness of chilled chicken.

[Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer].

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

[Implement of mixed reality navigation based on multimodal imaging in the resection of intracranial eloquent lesions].

Objective: To examine the clinical feasibility of mixed reality navigation (MRN) technology based on multimodal imaging for the resection of intracranial eloquent lesions. Methods: Fifteen patients with intracranial eloquent lesions admitted to the Department of Neurosurgery, the First Medical Center, People's Liberation Army General Hospital from September 2020 to September 2021 were retrospectively enrolled. There were 7 males and 8 females, aged (50±16) years (range: 16 to 70 years). Postoperative pathological diagnosis included meningioma (n=7), metastatic carcinoma (n=3), cavernous hemangioma, glioma, ependymoma, aneurysmal changes and lymphoma (n=1, respectively). The open-source software was used to perform the three-dimensional visualization of preoperative images, and the self-developed MRN system was used to perform the fusion and interaction of multimodal images, so as to formulate the surgical plan and avoid damaging the eloquent white matter fiber tracts. Traditional navigation, intraoperative ultrasound and fluorescein sodium angiography were used to determine the extent of lesion resection. The intraoperative conditions of MRN-assisted surgery were analyzed, and the setup time and localization error of MRN system were measured. The changes of postoperative neurological function were recorded. Results: MRN based on multimodal imaging was achieved in all patients. The MRN system setup time (M(IQR)) was 36 (12) minutes (range: 20 to 44 minutes), and the localization error was 3.2 (2.0) mm (range: 2.6 to 6.7 mm). The reliability of eloquent white matter fiber tracts localization based on MRN was rated as "excellent" in 11 cases, "medium" in 3 cases, and "poor" in 1 case. There were no perioperative death and no new impairment in motor, language, or visual functions after operation. Transient limb numbness occurred in 1 patient after operation, and recovered to the preoperative state in 2 weeks after operation. Conclusion: The MRN system based on multimodal imaging can improve the surgical accuracy and safety, and reduce the incidence of iatrogenic neurological dysfunction.

Distinct genomic landscapes of gastroesophageal adenocarcinoma depending on PD-L1 expression identify mutations in RAS-MAPK pathway and TP53 as potential predictors of immunotherapy efficacy.

BACKGROUND: The impact of molecular alterations on programmed death-ligand 1 (PD-L1) combined positive score (CPS) is not well studied in gastroesophageal adenocarcinomas (GEAs). We aimed to characterize genomic features of tumors with different CPSs in GEAs. PATIENTS AND METHODS: Genomic alterations of 2518 GEAs were compared in three groups (PD-L1 CPS ≥ 10, high; CPS = 1-9, intermediate; CPS < 1, low) using next-generation sequencing. We assessed the impact of gene mutations on the efficacy of immune checkpoint inhibitors (ICIs) and tumor immune environment based on the Memorial Sloan Kettering Cancer Center and The Cancer Genome Atlas databases. RESULTS: High, intermediate, and low CPSs were seen in 18%, 54% and 28% of GEAs, respectively. PD-L1 positivity was less prevalent in women and in tissues derived from metastatic sites. PD-L1 CPS was positively associated with mismatch repair deficiency/microsatellite instability-high, but independent of tumor mutation burden distribution. Tumors with mutations in KRAS, TP53, and RAS-mitogen-activated protein kinase (MAPK) pathway were associated with higher PD-L1 CPSs in the mismatch repair proficiency and microsatellite stability (pMMR&MSS) subgroup. Patients with RAS-MAPK pathway alterations had longer overall survival (OS) from ICIs compared to wildtype (WT) patients [27 versus 13 months, hazard ratio (HR) = 0.36, 95% confidence interval (CI): 0.19-0.7, P = 0.016] and a similar trend was observed in the MSS subgroup (P = 0.11). In contrast, patients with TP53 mutations had worse OS from ICIs compared to TP53-WT patients in the MSS subgroup (5 versus 21 months, HR = 2.39, 95% CI: 1.24-4.61, P = 0.016). CONCLUSIONS: This is the largest study to investigate the distinct genomic landscapes of GEAs with different PD-L1 CPSs. Our data may provide novel insights for patient selection using mutations in TP53 and RAS-MAPK pathway and for the development of rational combination immunotherapies in GEAs.

Investigating the Potential Mechanism of Pydiflumetofen Resistance in Sclerotinia sclerotiorum.

The necrotrophic pathogen Sclerotinia sclerotiorum is one of the most damaging and economically important plant pathogens. Pydiflumetofen, which was developed by Syngenta Crop Protection, has already been registered in China for the management of Sclerotinia stem rot, which was caused by S. sclerotiorum in oilseed rape. In an attempt to preempt and forestall the development of resistance to this useful fungicide, the current study was initiated to investigate the potential mechanism of resistance in laboratory mutants. Five pydiflumetofen-resistant S. sclerotiorum mutants were successfully generated by repeated exposure to the fungicide under laboratory conditions. Although the mutants had greatly reduced sensitivity to pydiflumetofen, they were also found to have significantly (P < 0.05) reduced fitness, exhibiting reduced mycelial growth and sclerotia formation on potato dextrose agar medium. However, three of the four mutants had significantly (P < 0.05) increased pathogenicity on detached soybean leaves compared with their respective parental isolates, indicating a moderate to high level of fungicide resistance risk according to the criteria of the Fungicide Resistance Action Committee. Sequence analysis of four succinate dehydrogenase (Sdh) target genes identified several nucleotide changes in the sequences of the pydiflumetofen-resistant mutants, most of which were synonymous and caused no changes to the predicted amino acid sequences. However, all of the pydiflumetofen-resistant mutants had two amino acid point mutations (A11V and V162A) in their predicted SsSdhB sequence. No similar changes were found in the SsSdhA, SsSdhC, and SsSdhD genes of any of the mutants tested. In addition, there was a positive cross-resistance between pydiflumetofen and boscalid, and no cross-resistance between pydiflumetofen and other commonly used fungicides, including tebuconazole, fludioxonil, cyprodinil, dimethachlone, prochloraz, pyraclostrobin, fluazinam, procymidone, and carbendazim. These results indicate that pydiflumetofen has great potential as an alternative fungicide for the control of S. sclerotiorum, especially where resistance to other fungicides has already emerged. Mixing or alternate application with fludioxonil, prochloraz, and fluazinam could be used to limit the risk of resistance to pydiflumetofen.