[Analysis of compliance with lung protective mechanical ventilation strategy in patients with acute respiratory distress syndrome].

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH2O or driving pressure≤15 cmH2O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ2=13.124, P=0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH2O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH2O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ2=10.464, P=0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ2=11.016, P=0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P<0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P>0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.

[Orodental phenotype and genotype findings in 8 Chinese children with hypophosphatasia].

Objective: To analyze the oral phenotype and gene variation of children with hypophosphatasia (HPP), and explore the genotype-phenotype correlations. Methods: Eight children diagnosed with HPP from January 2008 to January 2023 in Children's Hospital,Zhejiang University School of Medicine were recruited in this study. The pathogenic genes of 5 of them were sequentially analyzed and all of their oral manifestations, laboratory tests and genetic variation types were retrospectively analyzed. Results: A total of 8 children were recruited in the study, 3 males and 5 females, aged from 20 months to 104 months, whose main complaints were premature deciduous tooth loss. Among them, 3 children were diagnosed with odonto HPP, and the other 5 children were diagnosed with childhood HPP, including 2 children was odonto HPP at the first diagnosis and modified as childhood HPP at the age of 5. The age range of first deciduous tooth loss is 9 to 18 months, and the age range of diagnosis is 20 to 104 months. The patients of odonto HPP only showed premature loss of deciduous anterior tooth, while the patients with childhood HPP also showed premature loss of multiple deciduous molars. Panoramic radiographic film revealed enlarged pulp chambers and radicular canals in some primary and permanent teeth. The enamel hypoplasia, hypoplastic short roots, and alveolar resorption of deciduous molar were observed in some cases. The serum alkaline phosphatase (ALP) (30-107 U/L) levels of all the patients were lower than that in the normal children of same age and gender, and the ALP value of the 1-3 years old girls with childhood HPP (30-33 U/L) was lower than that of the three children with odonto HPP (61-107 U/L), but there was no significant difference in statistical analysis. There were 8 variation sites of ALP liver/bone/kidney (ALPL) gene detected in 5 children and their families, all of which were missense variation, including the new variants in the mutations of c.1334C>G(p.Ser445Cys) and c.1259G>T(p.Gly420Val) that were not reported in the literature. One case was autosomal dominant inheritance and other 4 cases were complex heterozygous variation with autosomal recessive inheritance. Conclusions: Pediatric stomatologists are often the first doctors to detect childhood and odonto HPP. Diagnosis of mild HPP is often delayed. The severity of HPP is related to serum ALP level and ALPL gene mutation sites.

[International comparison and assessment of the quality of drug clinical trial implementation in China based on scientific regulatory system].

With the rapid development of clinical research and the continuous enhancement of innovation capability in China, the quality of clinical research under China's scientific regulatory system has drawn widespread attention. This study evaluated the quality results of China's drug clinical trials implementation, compared the scientific regulatory systems of clinical research quality between China and the United States, analyzed real-world clinical application on the approval of new anti-tumor drugs through clinical trials, in order to analyze China's status and level of clinical trial implementation quality in the international industry, and explore the advantages and value of China's clinical research scientific regulation by collecting clinical trial data inspections disclosed by regulatory agencies in both China and the United States, as well as verifying information on the approval of new anti-tumor drugs.

[Transanal drainage tube for prevention of anastomotic leak after anterior resection for rectal cancer: a meta-analysis].

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

[Analysis of whole-mouth taste function test results in 584 healthy adults].

Objective: To assess the taste function of healthy Chinese adults with the reliable whole-mouth taste test, and to analyze the correlation of taste function with age and gender. Methods: The clinical data of 584 participants reporting the normal sense of smell and taste from March 2019 to January 2020 in the Physical Examination Center of Beijing Anzhen Hospital were analyzed in the study, including 297 males and 287 females, aging (46.9±16.6) years. The subjects were divided into youth group (19-35 years old), middle aged group (36-50 years old), middle-elderly aged group (51-65 years old) and elderly group (66-80 years old). The taste test involved 5 tastants (sour, sweet, salty, umami and bitter) and 7 concentrations. The perception and recognition scores of five tastes were obtained through the whole-mouth taste test. SPSS 22.0 software was used for statistical analysis. Results: The intra-class correlation coefficients of the whole-mouth taste test were 0.751 to 0.828, which showed high test-retest reliability. The total score of perception and recognition of five tastes showed the significant negative correlation with age (r value was -0.49 and -0.44, respectively, both P<0.001). Compared with the other two groups, taste function of middle-elderly aged and elderly group decreased significantly (all P<0.001). There was no significant difference in total perception scores and total recognition scores between youth and middle aged group (all P>0.05). The perception scores and recognition scores of sour, salty, umami, bitter and total scores in females were higher than those in males (all P<0.05), but there was no significant difference in perception scores and recognition scores for sweet between them (P value was 0.584 and 0.223, respectively). Conclusions: The taste function is significantly negatively correlated with age. Except the sweet, females are more sensitive to the sour, salty, umami and bitter tastes than males.

[Prognosis and related risk factors of acute respiratory distress syndrome in elder patients].

Objective: To study the risk factors associated with the hospital survival rate of elder patients with acute respiratory distress syndrome (ARDS) in Medical/Respiratory Intensive Care Units (MICUs/RICUs) by evaluating the prognosis, and therefore to provide insight into patient treatment strategy. Methods: Twenty MICUs/RICUs of 19 general hospitals in mainland China participated in the multicenter prospective cohort study carried out from Mar 1st, 2016 to Feb 28th, 2018. Patients who met the criteria of Berlin ARDS and older than 65 years were recruited. Baseline data, risk factors of ARDS, ventilator setup and prognosis data were collected from all patients. Univariant and multivariant regression analysis were conducted to analyze the factors associated with the prognosis. Results: 170 elder ARDS patients (age≥65 years) met the Berlin ARDS criteria, among whom 8.8% (15/170), 42.9% (73/170) and 48.2% (82/170) patients had mild, moderate and severe ARDS, respectively. The most common predisposing factor for elder ARDS was pneumonia, which was present in 134 patients (78.8%). 37.6% (64/170) patients were treated with noninvasive mechanical ventilation (NIV), but 43.8% (28/64) cases experienced treatment failure. 76.5% (130/170) patients were treated with invasive mechanical ventilation. All patients 80 years or older were given invasive mechanical ventilation. 51.8% (88/170) cases had complications of non-pulmonary organ failure. 61.8% (105/170) patients deceased during hospital stay. Multivariant logistic analysis showed that the independent risk factors for hospital survival rate in elder patients with ARDS were SOFA score (P=0.030, RR=0.725, 95% CI 0.543-0.969), oxygen index after 24 hours of ARDS diagnosis (P=0.030, RR=0.196, 95% CI 0.045-0.853), accumulated fluid balance within 7 days after diagnosis of ARDS (P=0.026, RR=1.000, 95% CI 1.000-1.000) and shock (P=0.034, RR=0.140, 95% CI 0.023-0.863). Conclusion: Among 20 ICUs, the high mortality rate of elder patients with ARDS was correlated with higher 24 hour SOFA score, lower 24 hour oxygen index after ARDS diagnosis, more positive fluid balance within 7 days and concomitant shock. The conservative fluid strategy within 7 days of ARDS diagnosis may benefit the elder ARDS patients.

B subgroup detection in a small hospital transfusion service.

The ABO blood group system includes phenotypes, or subgroups, that differ in the amount of A and B antigens present on the red blood cells (RBCs). These subgroups also differ in the A, B, or H substances present in secretions (for individuals who have the secretor phenotype). B subgroups are very rare and are less frequently reported than A subgroups. Usually, B subgroups are discovered during serologic testing when there is a discrepancy between RBC and serum grouping results. Subgroups of B are usually identified by a reference laboratory using molecular and adsorption-elution methods. This report details a case of a young, healthy, pregnant woman with a B subgroup detected by a small transfusion service using adsorption-elution methods. Serology and genotyping of the ABO gene was performed at a reference laboratory where the serology was consistent with a B subgroup, but no changes were identified in ABO gene sequencing. It is important to correctly identify B subgroups in donors and recipients to help resolve ABO discrepancies and potentially prevent ABO incompatibility in blood transfusion, thus minimizing transfusion reactions.The ABO blood group system includes phenotypes, or subgroups, that differ in the amount of A and B antigens present on the red blood cells (RBCs). These subgroups also differ in the A, B, or H substances present in secretions (for individuals who have the secretor phenotype). B subgroups are very rare and are less frequently reported than A subgroups. Usually, B subgroups are discovered during serologic testing when there is a discrepancy between RBC and serum grouping results. Subgroups of B are usually identified by a reference laboratory using molecular and adsorption-elution methods. This report details a case of a young, healthy, pregnant woman with a B subgroup detected by a small transfusion service using adsorption-elution methods. Serology and genotyping of the ABO gene was performed at a reference laboratory where the serology was consistent with a B subgroup, but no changes were identified in ABO gene sequencing. It is important to correctly identify B subgroups in donors and recipients to help resolve ABO discrepancies and potentially prevent ABO incompatibility in blood transfusion, thus minimizing transfusion reactions.

[Progress on clinical trials of cancer drugs in China, 2020].

Objective: To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019. Methods: Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020. Results: A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism (P>0.05). Conclusions: During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

[Analysis of factors affecting olfactory disfunctions in patients with chronic rhinosinusitis with nasal polyps].

Objective: To analyze the factors affecting olfactory disfunctions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: This was a retrospective analysis. Eighty-eight patients with CRSwNP who underwent endoscopic sinus surgery in Beijing Anzhen Hospital from 2014 to 2018 were enrolled, including 22 males and 66 females, with the age of (48.1±11.3) years old(Mean±SD). Sniffin' Sticks olfactory test, Lund-Mackay score and modified sinus CT olfactory cleft score, nasal resistance and acoustic reflex examination, blood routine and blood biochemistry test, serum specific IgE test were performed before surgery and nasal polyps of all patients were collected for eosinophil count during surgery. According to bilateral total TDI score, the patients were divided into normal olfactory function group and olfactory disfunction group. The clinical baseline data were compared between the two groups. According to the results of single factor analysis, factors which were significant different between the two groups and clinically useful indicators were further included in the multivariate Logistic regression model analysis, then a model predicting olfactory disfunction in patients with CRSwNP was initially established. P<0.05 was considered statistically significant. Results: Among 88 patients with CRSwNP, 32 (36.4%) patients were with normal olfaction and 56 (63.6%) patients were with olfactory disfunction, including 40 (45.5%) of hyposmia and 16 (18.2%) of anosmia. Tissue eosinophil count, blood eosinophil percentage and blood urea concentration had significant difference between the two groups (12.7[2.0, 52.3]/HP (M[P(25), P(75)]) vs 38.6[16.2, 87.0]/HP, 2.75[1.60, 4.80]% vs 4.35[2.50, 6.60]%, (5.56±1.15) mmol/L vs (4.98±1.33) mmol/L, all P<0.05). Modified sinus CT olfactory cleft score and Lund-Mackay score except for ostiomeatal complex score were statistically significant between the two groups (all P<0.05). Multivariate Logistic regression analysis showed that the bilateral and total olfactory cleft score and blood urea concentration were statistically significant, in addition, the bilateral and total olfactory cleft score was a risk factor (OR=2.108, 95%CI: 1.407-3.159, P<0.001) and blood urea within a certain concentration was a protective factor (OR=0.461, 95%CI: 0.240-0.884, P=0.020). Further studies found that the area under the ROC curve of the model with tissue eosinophil count, blood eosinophil percentage, bilateral and total olfactory cleft score, total inspiratory volume and blood urea concentration was 0.888 (P<0.01), which had good predictive value for olfactory disorders in CRSwNP. Conclusions: The modified sinus CT olfactory cleft score is closely related to the olfactory disorders in patients with CRSwNP. A certain degree of elevated blood urea concentration may have a protective effect on the olfactory function of patients with CRSwNP.

[Progress on clinical trials of cancer drugs in China, 2019].

Objective: To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019. Methods: The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted. Results: There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019. Conclusions: Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

[A review of immune-related adverse events associated with immunotherapy].

Immune checkpoint inhibitors have been approved for clinical application in China. However, the increased immune-related adverse event (irAE) needs more attention. This review summarized the incidence, characteristic clinical manifestation and treatment of irAEs associated with programmed cell death protein-1(PD-1) and programmed cell death ligand-1(PD-L1) inhibitors. To have a deep insight into irAE, the potential mechanisms, the different incidences of cancer types, influencing factors and the direction of future research were also discussed here to provide guidance for clinical oncologist to identify and monitor irAE.

[Preliminary investigation of gender assignment in 46,XY disorders of sex development with severe male undermasculinisation].

Objective: To explore the feasibility of gender assignment in 46,XY disorders of sex development (DSD) with severe undermasculinisation mainly based on molecular diagnosis. Methods: A retrospective study of 45 patients of 46, XY DSD with severe undermasculinisation were admitted between November 2015 and October 2018 at Children's Hospital, Zhejiang University School of Medicine. The initial social gender were all female, of whom the external genital manifestations were Prader 0 to 2; the degree of masculinity was scored using external masculinisation score (EMS); the position and development of the gonads were examined by ultrasound, cystoscopy and laparoscopy, also including assessing the development of the Wolffian tube and the Müllerian tube. The level and ratio of testosterone to dihydrotestosterone before and after hCG stimulation were evaluated for the function of Leydig cell and 5α-reductase-2. Gender role scales and sandbox games were used to assess gender role behavior. Genital sensitivity to androgen stimulation was assessed; A panel including 163 genes related to gender development were determined by second-generation sequencing in all 45 patients. Finally, a multidisciplinary team (MDT) makes a gender assignment after a comprehensive analysis mainly based on the molecular etiological diagnosis. Results: Thirty-nine out of 45 patients (87%) had an identifiable genetic etiology, and the remaining 6 (13%) were negative for genetic testing. Forty-five patients had EMS less than or equal to 3 points. Sexual psychological assessment was performed in 39 patients, with male dominance in 24 (62%) and female dominance in 15 (38%). The gender assignment was 23 cases (51%) for male and 19 cases (42%) for female, and 3 cases (7%) were not completely determined. Conclusions: Molecular diagnosis provides a strong basis for appropriate gender assignment of 46, XY DSD children with severe undermasculinisation. Based on molecular diagnosis, each DSD should be analyzed by professional MDT to analyze the clinical symptoms/signs, gonadal development, gonad tumor risk, external genital morphology, sexual psychological assessment, potential fertility opportunities, parental views, Social and cultural factors, etc. make appropriate gender assignment.

[Effect of endoscopic sinus surgery on olfactory function in patients with chronic rhinosinusitis with nasal polyps].

Objective:To evaluate the effect of surgery on olfactory function in patients with chronic rhinosinusitis with nasal polyps（CRSwNP） by subjective and objective olfactory tests. Method:This was a retrospective study. Forty patients with CRSwNP who underwent endoscopic sinus surgery（ESS） from 2015 to 2017 in Beijing Anzhen Hospital were enrolled. Postoperative time was 6-46 months. The patients were followed up in October 2018 and examined using Sniffin' sticks olfactory test and olfactory event-related potentials （oERP）. The polyps collected during surgery were performed to eosinophil count and percentage calculation. They were divided into eosinophilic CRSwNP（ECRS） and non-eosinophilic CRSwNP（NECRS）. The subjective and objective olfactory functions between the two groups were compared before and after surgery respectively and the paired T test was performed between the postoperative and the preoperative Sniffin' sticks olfactory test. Covariance analysis was used to adjust the effect of different postoperative time on postoperative olfactory recovery. Result:There were 21（52.5%） ECRS and 19（47.5%） NECRS patients of the 40 patients with nasal polyps. There was statistical difference in the posterior ethmoid score and the posterior olfactory cleft score of CT. According to the criterion of total TDI increased more than 5.5, olfactory function in 21（52.5%） patients had improved. In addition, there was a significant improvement in olfactory function in ECRS group either in unilateral T/TDI or bilateral T/D/TDI, but only unilateral T/TDI increased in NECRS group. There was no significant difference in Sniffin' sticks olfactory test between the two groups, but there was a statistically significant difference in the latency of oERP after surgery. Conclusion:ESS could improve olfactory function in patients with CRSwNP by more than 50%. Bilateral olfactory improvement in ECRS was better than that in NECRS, but olfactory function in postoperative ECRS was still lower than that in NECRS. oERP can more objectively and accurately reflect the severity of olfactory disorders associated with eosinophilic inflammation.

[The clinical reports on adrenal insufficiency of patients with advanced solid tumors accepting anti-PD-1 antibody, SHR-1210 therapy].

Objective: To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy. Methods: The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency. Results: Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210. Conclusions: The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.

Heat-induced protein oxidation of soybean meal impairs growth performance and antioxidant status of broilers.

This study aimed to evaluate the impact of oxidative modification on soybean meal (SBM) proteins after exposure to different heating times, and the effects of the oxidized SBM on the growth performance [average daily feed intake (ADFI), average daily gain (ADG), and feed to gain ratio (F: G)], oxidative redox status [(reactive oxygen species (ROS), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and protein carbonyl (PC)]. A total of 400 one-day-old Arbor Acres chicks were randomly divided into 5 treatment groups with 8 replicates of 10 birds each. Birds in the control group (CON) were fed diet containing non-heated SBM, and those in the treatment groups were fed SBM heated at 100°C for 1, 2, 4, and 8 h, for 42 d. Heated SBM (HSBM) showed a relatively higher PC content in vitro. The ADG decreased, whereas the F:G increased linearly with an increase in heating time during the starter (days 1 to 21), grower (days 22 to 42), and the overall growth phases (days 1 to 42; P < 0.05). However, the ADFI decreased linearly only during the grower phase (P < 0.05). The plasma, liver, and jejunum ROS levels, MDA concentrations, and PC contents increased linearly (P < 0.05) in broilers fed HSBM. Furthermore, the TAC in the plasma and jejunum, and the total SOD and GSH-Px activities in the plasma, liver, and jejunum decreased linearly (P < 0.05) in broilers when feeding HSBM. (P < 0.05). The mRNA level of Nrf2 in the liver and jejunum was lower (P < 0.05) in broilers fed diet containing the SBM after 8 h heat-treatment than in those fed the CON diet at days 42. This study suggested that heat-induced protein oxidation of SBM could decrease growth performance and impair antioxidant status of broilers.

[Correlation of tissue eosinophil count and modified CT olfactory cleft score and olfactory function in patients with nasal polyps].

Objective:To investigate the effect of tissue eosinophil count on olfactory function in patients with chronic sinusitis with nasal polyps（CRSwNP）. Method:We prospectively selected 59 patients with CRSwNP. All the patients were not treated with oral or topical glucocorticoids for at least 1 month at the time of enrollment. All the nasal polyps were taken under local anesthesia in the outpatient department for eosinophil count and percentage calculation. The patients were divided into eosinophilic CRSwNP（ECRS group） and non-eosinophilic CRSwNP（non-ECRS group）. Baseline data was compared between the two groups. Spearman correlation analysis was performed on tissue eosinophil count and Lund-Mackay score, modified olfactory cleft scores, Sniffin' Sticks olfactory test, olfactory evoked potential peak latency and amplitude respectively. Result:Thirty-five of 59 patients with CRSwNP completed olfactory evoked potential test, from whom we collected stable waveforms. The ECRS group had a higher olfactory cleft area CT score, ethmoid sinus CT score and blood eosinophil count and percentage; there was a significant difference between the ECRS group and the non-ECRS group in single and bilateral odor test threshold（T value）（P=0.017）. There was no significant correlation between tissue eosinophil count and subjective olfactory VAS score（P>0.05）. Tissue eosinophil count was related to the bilateral T value in Sniffin' Sticks olfactory test（r=-0.322, P=0.013）, anterior and posterior olfactory cleft area scores（r=0.431 and 0.415, respectively, P=0.001） and olfactory evoked potential N1 latency（r=0.504, P=0.001） and P2 latency（r=0.374, P=0.020）, but not related to Lund-Mackay scores. In addition, there was a significant correlation between the unilateral T score in Sniffin' Sticks test and the unilateral olfactory evoked potential N1 latency（r=-0.505, P=0.002）. Conclusion:The increase of tissue eosinophilia was closely related to olfactory disfunctions in CRSwNP. It could be reflected by modified CT olfactory cleft score, Sniffin' Sticks olfactory test T value and oERP peak latency. In addition, T value was negatively consistent with latency of oERP N1 peak.

[Clinical observation of thyroid-related adverse events induced by anti-PD-1 antibody SHR-1210 in patients with advanced solid tumor].

Objective: To assess the incidence and characteristics of thyroid dysfunction during anti-Programmed cell death 1 receptor (PD-1) antibody SHR-1210 therapy in patients with advanced solid tumor. Methods: The medical records of 98 patients who initiated SHR-1210 treatment between April 27, 2016 and June 8, 2017 in the phase 1 trial to evaluate the safety, efficacy, and pharmacokinetics of SHR-1210 in patients with advanced solid tumors were retrospectively reviewed. Serological tests of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at baseline and prior to each SHR-1210 administration. Results: A total of 86 patients had normal thyroid function before the first dose of SHR-1210 treatment. Nine out of 86 (10.5%) patients developed new onset hypothyroidism from euthyroid state. 12 patients presented thyroid dysfunction at baseline, 10 of whom were subclinical hypothyroid and 2 were hypothyroidism. Four out of 10 patients developed hypothyroidism from subclinical hypothyroid. Most patients with hypothyroidism were asymptomatic. Thyroid dysfunction occurred early (median, 55days) after the initiation of SHR-1210. The severity of hypothyroidism were all grade 1-2. No grade 3-4 hypothyroidism occurred. No patients discontinue the treatment of SHR-1210 due to clinical impact of the thyroid dysfunctions. Conclusions: Thyroid-related adverse events were common during anti-PD-1 antibody SHR-1210 treatment . The incidence of hypothyroidism is lower in patients with euthyroid state than in patients with thyroid dysfunction at baseline during SHR-1210 treatment . Thyroid function can be improved after thyroid hormone replacement. During SHR-1210 treatment, it is necessary to pay attention to monitor the thyroid function, especially in the patients with thyroid dysfunction at baseline. Trial registration: Chinese Clinical Trial Registry, 2016L01455.