[Gastrointestinal tumors with SWI/SNF complex deficiency: a clinicopathological analysis of 36 cases].

Objective: To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients. Methods: Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed. Results: A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression (P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins (P<0.05). Conclusions: SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.

[Clinical study on the classification of renal artery involvement and comparison of renal function and prognosis of Stanford type B aortic dissection after thoracic aortic endovascular repair].

Objective: To investigate the different types of renal artery involvement in Stanford type B aortic dissection (TBAD) and the comparison of clinical effecacy after thoracic endovascular aortic repair (TEVAR). Methods: This is a retrospective cohort study included 330 patients with TBAD and renal artery involvement treated with TEVAR from June 2002 to September 2021 in General Hospital of Northern Theater Command of the PLA. According to aortic CTA image, unilateral renal artery involvement conditions were divided into 5 types: the true lumen type (renal artery opening completely from the true lumen), false lumen type (renal artery opening completely from the false lumen), double lumen type (renal artery opening from the true and false double lumen), compression type (renal artery opening connected with the true lumen, but the renal artery opening was extremely squeezed by the inner membrane), open type (renal artery opening with intimal tear). There were seven types of bilateral renal artery involvement: true-true type (true lumen-true lumen type), true and false type (true lumen-false lumen type), true-double type (true lumen-double lumen type), true-opening type (true lumen-opening type), false-false type (false lumen-false lumen type), false-compression type (false lumen-compression type), double-double type (double lumen-double lumen type). The primary observation index of this study was the comparison of postoperative renal function and the incidence of clinical adverse events of different types of renal artery involvement. One-way ANOVA test, Kruskal-Wallis H test and paired sample rank sum test were used to compare postoperative renal function between different types of bilateral renal artery involvement. The Chi-square test or Fisher's exact probability test were used to compare the near and long term adverse events between different types of bilateral renal artery involvement. Kaplan-Meier method was used to compare the all-cause mortality of patients with severe renal functional injury and non-severe renal functional injury before surgery. Results: The average age of the patients included in this study was (53±11) years, including 276 males (83.6%) and 54 females (16.4%). There were statistical difference in the level of serum creatinine (preoperative:H=18.686, P=0.005, postoperative:H=18.101, P=0.006) and cystatin C (preoperative:H=17.566, P=0.007, postoperative:H=10.433, P=0.016), pre-and post-operative, between the seven groups of TBAD patients with different renal artery involvement types (P<0.05), and the false-false type group shown the worst kidney function. However, no statistically significant differences were shown when comparing their pre- and post-operative change values (P>0.05). The 30-day follow-up result showed that there were statistically significant differences in the incidence of postoperative acute kidney injury (χ2=15.623, P=0.007), aorta-related adverse events (χ2=15.523, P=0.010), and intraoperative endoleak (χ2=17.935, P=0.004) among the seven groups, and the false-false group was the highest (2/9, 5/9 and 5/9, respectively). In terms of long-term follow-up results, there were statistically significant differences in all-cause death (χ2=14.772, P=0.011) and non-aortic death (χ2=15.589,P=0.008) among the seven groups. Kaplan-Meier survival analysis showed that patients with worse pre-operative renal function showed higher long-term all cause death (17.7% vs. 4.8%, P=0.009). Conclusions: For TBAD patients with renal artery involvement, there were differences in renal function among different types, and TEVAR showed no significant effect on renal function in TBAD patients. The long-term all cause death was higher in patients with worse renal function pre-operative.

[Research on rapid detection technology of airborne pathogenic organisms based on up-conversion phosphor technology].

Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 107 CFU/ml and 108 CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 104 CFU/ml. Detection sensitivity of Yersinia pestis ≥103 CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥103 CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 104 CFU/m3, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.

[Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis].

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

[Effect of out-hospital blood pressure management on prognosis of patients with acute aortic syndrome complicated with hypertension after TEVAR].

Objective: To investigate the influence of blood pressure control after discharge on prognosis of patients with acute aortic syndrome (AAS) complicated with hypertension who underwent thoracic endovascular aortic repair (TEVAR). Methods: This is a retrospective case analysis. Patients diagnosed with AAS complicated with hypertension and undergoing TEVAR in Northern Theater Command General Hospital from June 2002 to December 2021 were consecutively enrolled. Average systolic blood pressure (SBP) and the occurrence of endpoint events were recorded at one month, one year and every 2 years after TEVAR. According to the patients' average SBP, patients with average SBP<140 mmHg (1 mmHg=0.133 kPa) or<150 mmHg were divided into the target blood pressure achievement group, and the others were divided into target blood pressure non-achievement group. Endpoint events included all-cause death, aortic death, stroke, renal insufficiency, aortic related adverse events and a composite of these events (overall clinical adverse events), and re-accepting TEVAR. The incidence of endpoint events was compared between the two groups at each follow-up period. Results: A total of 987 patients were included, aged (55.7±11.7) years, including 779 male (78.9%). When the cutoff value was 140 mmHg, the rate of average target SBP achievement was 71.2% (703/987) at one month, 66.7% (618/927) during 1st to 12th month and 65.1% (542/832) from the first year to the third year after TEVAR. The proportion of patients taking≥2 antihypertensive agents was higher in the group of target blood pressure non-achievement group than the target blood pressure achievement group after TEVAR at 1 month (74.3% (211/284) vs.65.9% (463/703), P=0.010) and during 1st to 12th month (71.5% (221/309) vs. 63.6% (393/618), P=0.016). There were no statistical differences in the all-cause deaths, stroke, aortic related adverse events, and repeat TEVAR between the two groups (All P>0.05) during above follow-up periods. When the cutoff value was 150 mmHg, the rate of target SBP achievement was 89.3% (881/987) at one month, 85.2% (790/927) during 1st to 12th month and 85.6%(712/832) from the first year to the third year after TEVAR. The incidence of clinical total adverse events (8.8% (12/137) vs. 4.2% (33/790), P=0.021) and repeat TEVAR (4.4% (6/137) vs. 1.0% (8/790), P=0.003) in target blood pressure non-achievement group were significantly higher than the target blood pressure achievement group during 1st to 12th month after TEVAR. The incidence of all-cause deaths (5.8% (7/120) vs. 2.4% (17/712), P=0.037) in the target blood pressure non-achievement group was significantly higher than the target blood pressure achievement group from the first year to the third year follow-up period, but there were no statistical differences in the incidence of clinical total adverse events between the two group (P>0.05). Conclusion: Among TEVAR treated AAS patients complicated with hypertension, the average SBP more than 150 mmHg post discharge is associated with increased risk of adverse events. Ideal blood pressure control should be encouraged to improve the outcome of these patients.

Growth performance, digestibility, blood metabolites, ruminal fermentation, and bacterial communities in response to the inclusion of gallic acid in the starter feed of preweaning dairy calves.

The objective of this study was to evaluate the effects of feeding gallic acid on the growth, nutrient digestibility, plasma metabolites, rumen fermentation, and bacterial community in the rumen fluid and feces of preweaning calves. Thirty-six female Holstein calves with similar ages (means ± SD; 3.1 ± 1.39 d) and body weights (40.8 ± 2.87 kg) were randomly assigned to receive 3 treatments. Calves were fed 1 of 3 treatments as follows: basal diet with no gallic acid (control), 0.5 g/kg gallic acid in starter diet (low), and 1 g/kg gallic acid in starter diet (high). The results showed that feeding gallic acid increased growth by improving the starter intake and average daily gain of the calves. The fecal score tended to decrease in a linear manner with the addition of gallic acid. Total-tract apparent protein digestibility tended to increase linearly with feeding gallic acid. Feeding gallic acid led to a linear increase in the plasma total protein and ß-hydroxybutyrate levels. In addition, feeding gallic acid linearly increased catalase and total antioxidant capacity levels and decreased malondialdehyde and tumor necrosis factor-α concentrations. The concentrations of total volatile fatty acids, propionate, butyrate, and valerate in the rumen fluid increased linearly with the addition of gallic acid, resulting in a linear pH reduction. Feeding gallic acid linearly increased the relative abundances of Prevotella_1, Saccharofermentans, and Prevotellaceae_UCG-001 and linearly decreased the relative abundance of Prevotella_7 in the rumen fluid. The Shannon index of ruminal bacterial communities linearly increased by feeding gallic acid. Feeding gallic acid linearly increased the relative abundances of Ruminococcaceae_UCG-005, Bacteroides, and Christensenellaceae_R-7_group in the feces. In summary, feeding gallic acid improved growth, antioxidant function, and rumen fermentation and altered the bacterial community in the rumen fluid and feces of preweaning dairy calves.

[A 10-year retrospective analysis of spectrums and treatment options of orthostatic intolerance and sitting intolerance in children].

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ2= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

[Evaluation of the efficacy of a new variable frequency stimulation sacral neuromodulation in the treatment of detrusor hyperactivity with impaired contractility].

A total of 16 detrusor hyperactivity with impaired contractility (DHIC) patients who received 12 weeks remote variable frequency stimulation (VFS) were enrolled at the First Affiliated Hospital of Zhengzhou University from September 2020 to February 2021. The voiding diary, symptom score scales and incidence of complications were completed and recorded at baseline, constant frequency stimulation (CFS) and VFS phases. Compared with the CFS phase, voiding times, urge incontinence times and daily catheterization volume were reduced; average voiding amount and functional bladder capacity increased; and the quality of life score and mental health questionnaire assessment were improved in the VFS phase(all P<0.05). In the end, among all 16 patients, there were 14 whose symptoms had improved, and there were no new complications such as pain or infection at the implantation site, electrode displacement, and electric shock sensation in the stimulation area. VFS-SNM can not only improve the DHIC patients' lower urinary tract symptoms during storage and urination period, but also improve the patients' quality of life and satisfaction of the therapy.

Andrias davidianus ranavirus 1R encoding a delayed-early protein promotes cell proliferation by driving cell cycle progression into S phase.

Andrias davidianus ranavirus 1R (ADRV-1R), a core gene of the family Iridoviridae, is predicted to encode a viral transcription factor (vTF) since the protein contains a virus late transcription factor-3 like (VLTF3 like) domain. However, its characteristics and function are still unclear. In this study, the transcription and expression of ADRV-1R were investigated in Chinese giant salamander thymus cells (GSTCs). ADRV-1R transcription starts 6 hours post-infection (hpi), while the protein expression starts 8 hpi. Drug inhibition assay showed that the transcripts are inhibited by cycloheximide (CHX), a de novo protein synthesis inhibitor, indicating that ADRV-1R is a viral delayed-early (DE) gene. Subcellular localization showed that ADRV-1R is distributed in the cell nucleus and cytoplasm. The effect of ADRV-1R overexpression on cell proliferation and virus titer was analyzed. ADRV-1R overexpression significantly promoted the cell proliferation starting at day 2. Flow cytometry analysis further indicated that the protein promotes the GSTC cell cycle progression from G1 phase into S phase (G1/S transition). Moreover, ADRV-1R overexperession significantly increased ADRV titer in GSTCs. The virus titer was 6.3-6.9-fold higher at 36 hpi and further after than the control GSTC lines. These data showed that ADRV-1R is a delayed-early protein promoting cell proliferation and virus titers. Keywords: ranavirus; Andrias davidianus ranavirus; core gene; cell cycle; cell proliferations.

[Genetic expression differences of 11 beta-hydroxysteroid dehydrogenase in the bone microvascular endothelial cells derived from different regions of the human femoral head].

Objective: To investigate the expression levels and activation differences of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) gene in bone microvascular endothelial cells (BMECs) in different regions of human femoral head. Methods: Tissue specimens of femoral heads were obtained from hip arthroplasty carried out in China-Japan Friendship Hospital from January 2017 to June 2018. And the BMECs we isolated, purified, identified and cultured from different regions of the human femoral head: in the subchondral and cancellous bone regions. The BMECs from the two regions were intervened by hydrocortisone with a series of low concentration gradients (0, 0.03, 0.06, 0.10 mg/ml) respectively. The cell phenotype and functional status of BMECs and cell migration were detected by scratch experiments, and the angiogenesis in different regions of the femoral head was observed. The mRNA and protein expression of 11beta-HSD1, 11beta-HSD2 in BMECs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western-blot method, respectively. Results: With the increase of the concentration of hydrocortisone, the 11beta-HSD1 mRNA and protein expression of BMECs in the subchondral and cancellous bone regions of the femoral head increased significantly, and the 11beta-HSD1 mRNA and protein expression of BMECs in the subchondral bone region was significantly lower than those in cancellous bone region (all P<0.05). The 11beta-HSD2 mRNA and protein expression of BMECs in the cancellous bone region showed a slow decrease first and then increased slightly at 0.10 mg/ml, while the expression in the subchondral bone region was the opposite. The 11beta-HSD2 mRNA and protein expression of BMECs in subchondral bone region was slightly higher than those in cancellous bone region (all P<0.05), but there was no significant statistical difference between the two regions at 0.10 mg/ml (0.123±0.018 vs 0.126±0.021, 0.577±0.231 vs 0.609±0.174, t=1.380, 0.409, both P>0.05). At different times of the 0.06 mg/ml hydrocortisone intervention, there was no significant differences in scratch closure rate, the number of BMECs lumen, the number of buds and the length of tubule branches in different regions of the femoral head (all P>0.05). Conclusion: The 11beta-HSD expression of BMECs in different regions of human femoral head is significantly different. The 11beta-HSD1 is high-expressed, but 11beta-HSD2 is low-expressed in BMECs of the cancellous bone region, and those are opposite in the subchondral bone region, which helps to explain the pathological characteristics and pathogenesis of hormonal osteonecrosis.

[The mediating role of psychological capital between occupational stress and suicidal ideation].

Objective: To analyze the mediating effect of psychological capital (PsyCap) between occupational stress and suicidal ideation. Methods: In September 2017, stratified-cluster sampling method was adopted to select employees of an electronic manufacturing service industry as respondents for a questionnaire survey in Jiangsu province. The demographic characteristics of employees were collected. A total of 2 465 employees were investigated, and 2 216 valid questionnaires were collected. The level of occupational stress and PsyCap was assessed by the Effort-Reward Imbalance Scale(ERI)and PsyCap Questionnaire. Results: The age of 2 216 employees was (28.70±5.26) years old, including 1 230 males (55.5%). The scores of occupational stress on effort, reward and over-commitment were (3.08±0.63), (3.73±0.60) and (2.51±0.68), respectively. The average ERI index (ratio of effort to return) was (0.88±0.39). The total score of PsyCap was (86.62±15.23). The detection rate of suicidal ideation within two weeks was 13.9% (309/2 216). The average score of effort and over-commitment and the ERI index were positively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about 0.081, 0.141 and 0.164, respectively. The average score of reward and total score of PsyCap were negatively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about -0.206 and -0.228, respectively. The mediating effect results showed that PsyCap had mediating effect on the effort, reward, over-commitment and suicidal ideation of occupational stress respectively, with mediating effect values of -0.087 (95%CI: -0.018,-0.019), -0.299 (95%CI: -0.428,-0.200) and 0.096 (95%CI: 0.0394, -0.170). The mediating effect percentages were 9.43%, 17.92%, and 9.54%, respectively. Conclusion: PsyCap has a mediating effect between effort, reward, over-commitment of occupational stress and suicidal ideation.

[Development of the Core Occupational Stress Scale for occupational populations in China].

Objective: To develop the Core Occupational Stress Scale (COSS) for key occupational populations, and to assess the reliability and validity of COSS in China. Methods: According to the literature review, in-depth interview and expert evaluation, the item pool of COSS was established. A total of 20 981 employees (3 703 employees from 2018 and 17 178 employees from 2019) of manufacturing, medical, and traffic polices, etc. from Beijing, Tianjin, Shanghai, Chongqing, Jiangsu, Shandong, Zhejiang, Hunan, Guangdong and Hubei were investigated using convenient sampling of those participating in general or occupational health examination of the day. Item differential test and exploratory factor analysis (EFA) were used to screen items from the item pool; confirmatory factor analysis (CFA) was used to test structure validity; criterion and convergent validity were tested by Pearson correlation. Cronbach's α coefficient was used to test the reliability of the scale. Results: The EFA suggested a four-factor structure for a 17-item version of COSS, which were social support, organization and reward, demand and effort, and control. It explained 62.06% of the total variance and factor loadings ranged from 0.447 to 0.918. The CFA confirmed the hypothesized four-factor model (GFI=0.904, CFI=0.912, RMSEA=0.079). The COSS scores were positively correlated with burnout, depressive symptoms, and effort-reward imbalance scores with r ranging from 0.357 to 0.567 (P<0.05). The total COSS and each dimension of Cronbach's α coefficients were 0.772-0.896. Conclusions: The COSS has good reliability and validity and can be used as an occupation stress assessment for occupational populations in China.

[Pathological features of immune-mediated hepatitis due to immune checkpoint inhibitors and anti-angiogenesis targeted therapy].

Objective: To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy. Methods: Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining. Results: Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. Conclusion: Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.

Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432.

BACKGROUND: High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1. PATIENTS AND METHODS: We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1-d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy. RESULTS: In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24-0.96), P = 0.038], while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs. CONCLUSIONS: Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT02915432.

[Analysis of the effects and influencing factors of thymectomy for myasthenia gravis].

Objective: To explore the effects of surgical treatment for myasthenia gravis as well as its influencing factors. Methods: A total of 180 patients with myasthenia gravis who underwent thymectomy from August 2012 to September 2018 were enrolled. Clinical data such as age, gender, disease classification, preoperative AChR-Ab, preoperative course, operation time, intraoperative blood loss, and pathological type was retrospectively reviewed. Univariate analysis and Cox regression model were used to analyze possible influencing factors of surgical effects. Results: A total of 145 patients were finally enrolled and the follow-up period was from 4 to 78 months, with a median follow-up time of 34 months. Thirty-four patients (23.4%) achieved complete stable remission (CSR). The total clinical remission and effective rate reached 75.1% (109 cases) and 89.6% (130 cases), respectively. Correlation analysis showed that age below 45 years old, preoperative course within 12 months, positive AChR-Ab and thymic hyperplasia were clinical influencing factors for better surgical results (P=0.030, 0.048, 0.019 and 0.042, respectively). Conclusions: It is safe and effective to undergo thymectomy for myasthenia gravis. Age, preoperative course, AChR-Ab level and pathological type were the influencing factors of surgical effects.

Genetic study of early-onset Graves' disease in the Chinese Han population.

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1-Mb region of the FOXP3 gene, and 20 validated GD-risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region-rs4947296-was more strongly correlated with early-onset GD than non-early-onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤20 years.

Percutaneous transforaminal endoscopic discectomy and miniincision surgery in the treatment of lumbar intervertebral disc protrusion.

Lumbar intervertebral disc protrusion (LIDP) is a frequently occurring disease and 10-20% of patients require surgical treatment. Percutaneous transforaminal endoscopic discectomy (PTED) and mini-incision surgery are currently the most common surgeries for patients. To analyze the efficacy of PTED and mini-incision surgery in the treatment of lumbar intervertebral disc protrusion, this study selected 216 patients with LIDP who were admitted to the hospital between February 2014 and June 2015. The subjects were randomly divided into an observation group and a control group, 108 each. Patients in the observation groups were treated by PTED, while patients in the control group were treated by mini-incision surgery, and treatment efficacy of the two groups was observed. The results demonstrated that the duration of surgery and length of hospital stay of the observation group were significantly shorter than those of the control group, the intraoperative blood loss of the observation group was significantly less than that of the control group and the size of surgical incision of the observation group was much smaller than that of the control group (P less than 0.05). As to clinical efficacy, in accordance with the Japanese Orthopaedic Association (JOA) score and the Visual Analogue Scale (VAS) score, results of the observation group were superior to those of the control group at 3 months after surgery (P less than 0.05). In conclusion, treating patients with LIDP through PTED can significantly improve treatment efficacy, shorten surgical and healing time and relieve pain. This therapy is worth clinical promotion.

[Clinical value of pegylated interferon-α plus ribavirin-based therapy in antiviral treatment of chronic hepatitis C in China].

Chronic hepatitis C virus (HCV) infection is one of the most common causes of liver cirrhosis and hepatocellular carcinoma in China. The older standard treatment regimen for chronic hepatitis C was the pegylated interferon-alfa plus ribavirin(PR). Now newer oral medications called direct antiviral agents (DAAs) has been gradually changed to PR-based DAAs and interferon-free, oral DAAs; making chronic hepatitis C a curable disease. This article intends to expound the advantages and disadvantages of PR-based therapy and provide reference for the treatment of chronic hepatitis C.

Use of microbial indicators combined with environmental factors coupled with metrology tools for discrimination and classification of Luzhou-flavoured pit muds.

AIMS: Pit mud is essential for the quality and yield of Chinese Luzhou-flavoured liquor. A reliable and fast method based on the use of microbial indicators combined with environmental factors coupled with metrology tools is needed to discriminate and classify different maturity levels of Luzhou-flavoured pit muds. METHODS AND RESULTS: Firmicutes, Bacteroidetes, Actinobacteria, Lactobacillus, Bacillus, Methanosarcina, Methanocorpusculum, Methanoculleus and Clostridium kluyveri were microbial indicators in Luzhou-flavoured pit muds. They were detected by real-time quantitative PCR. Environmental factors investigated included moisture content, pH, total acid and ammonia nitrogen. Principal component analysis (PCA) and partial least square-discriminant analysis were employed to explore the structure of the data and construct discrimination and classification models by reduction in the data dimensionality. Pit muds were distinguished and classified as new, trend to-be aged and aged. Moisture content and pH were significantly negatively correlated with new pit mud, while pH, total acid, amino nitrogen, Firmicutes, Bacteroidetes, Actinobacteria, Methanosarcina, Methanoculleus and C. kluyveri were significantly positively correlated with aged pit mud. CONCLUSIONS: Microbial indicators combined with environmental factors coupled to metrology tools can reliably and quickly discriminate and classify different maturity levels of Luzhou-flavoured pit muds. SIGNIFICANCE AND IMPACT OF THE STUDY: Modern techniques and metrology tools verified the correctness of the traditional sensory evaluation used in controlling the quality of pit mud, and will contribute to distinguishing different maturity levels of Chinese Luzhou-flavoured pit muds.

Efficacy and safety of fosaprepitant in the prevention of nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study.

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.