Tianjin Medical University General Hospital Research Articles

EARLY INITIATION OF RENAL REPLACEMENT THERAPY IN INTENSIVE CARE UNIT PATIENTS WITH BOTH ACUTE RESPIRATORY DISTRESS SYNDROME AND SEPSIS WITH OR WITHOUT RENAL FAILURE: A RETROSPECTIVE COHORT STUDY BASED ON PROPENSITY SCORE MATCHING.

Background: It is unknown whether early renal replacement therapy (RRT) initiation strategy in intensive care unit (ICU) patients with both acute respiratory distress syndrome (ARDS) and sepsis with or without renal failure is clinically beneficial. Patients and methods: A total of 818 patients with both ARDS and sepsis admitted to the ICU of Tianjin Medical University General Hospital were included in the analysis. Early RRT was defined as initiating the RRT strategy within 24 h of admission. The relationship between early RRT and clinical outcomes, including primary (30-day mortality) and secondary (90-day mortality, serum creatinine, Pa o2 /Fi o2 , duration of invasive mechanical ventilation, cumulative fluid output, and cumulative fluid balance) outcomes, was compared using propensity score matching (PSM). Results: A total of 277 patients (33.9% of the total population) underwent an early RRT initiation strategy before PSM. After PSM, a cohort of 147 patients with early RRT and 147 patients without early RRT with matched baseline characteristics (including serum creatinine at admission) were constructed. Early RRT was not significantly associated with 30- (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.85; P = 0.258) or 90-day mortality (HR, 1.30; 95% CI, 0.91-1.87, P = 0.150). At each time point within 72 h after admission, there was no significant difference in serum creatinine, Pa o2 /Fi o2 and duration of mechanical ventilation between the early and the no early RRT groups. Early RRT significantly increased total output at all time points within 72 h of admission and reached a statistically significant negative fluid balance at 48 h. Conclusions: Early RRT initiation strategies had no statistically significant survival benefit in ICU patients with both ARDS and sepsis, with or without renal failure, nor did they significantly improve serum creatinine and oxygenation or shorten the duration of mechanical ventilation. The use and timing of RRT in such patients should be thoroughly investigated.

Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women.

Atrophy of the reproductive tract mucosa caused by the decrease of estrogen may increase the detection rate of ASC-US in cervical cytology of post-menopausal women. In addition, other pathogenic infections and inflammation can change the cellular morphology and increase the detection rate of ASC-US. However, further studies are needed to elucidate whether the high detection rate of ASC-US in post-menopausal women leads to the high referral rate of colposcopy. This retrospective study was conducted to document ASC-US in cervical cytology reports at the Department of Cytology at Gynecology and Obstetrics, Tianjin Medical University General Hospital between January 2006 and February 2021. We then analyzed 2,462 reports of women with ASC-US at the Cervical Lesions Department. A total of 499 patients with ASC-US and 151 cytology with NILM participants underwent vaginal microecology tests. The average reporting rate of ASC-US in cytology was 5.7%. The detection rate of ASC-US in women aged > 50 years (7.0%) was significantly higher than that in women aged ≤50 years (5.0%) (P<0.05). The CIN2+ detection rate was significantly lower in the post- (12.6%) than in pre-menopausal (20.5%) patients with ASC-US (P <0.05). The prevalence of abnormal reporting rate of vaginal microecology was significantly lower in the pre-menopausal group (56.2%) than that in the post-menopausal group (82.9%) (P<0.05). The prevalence of bacterial vaginosis (BV) (19.60%) was relatively high in the pre-menopausal group, but the abundance of bacteria-inhibiting flora (40.79%) was mainly an abnormality in the post-menopausal group. The vaginal microecological abnormality rate of the women with HR-HPV (-) of ASC-US was 66.22%, which was significantly higher than that of the HR-HPV (-) and the NILM group (52.32%; P<0.05). The detection rate of ASC-US in women aged > 50 years was higher than that ≤50 years, but the detection rate of CIN2+ was lower in the post-menopausal women with ASC-US. However, vaginal microecological abnormalities may increase the false-positive diagnosis rate of ASC-US. The vaginal microecological abnormalities of the menopausal women with ASC-US are mainly attributed to infectious diseases such as BV, and it mainly occurs in the post-menopausal women was bacteria-inhibiting flora. Therefore, to avoid the high referral rate for colposcopy, more attention should be paid to the detection of vaginal microecology.

Hyperuricemia as an effect modifier of the association between metabolic phenotypes and nonalcoholic fatty liver disease in Chinese population

BackgroundDifferent metabolic phenotypes may be related to nonalcoholic fatty liver disease (NAFLD), but such association whether modified by serum uric acid levels is unknown. We examined the association between different metabolic phenotypes and NAFLD and further explore whether hyperuricemia could modify this association.MethodsA total of 2959 participants (mean age: 55.02 years) with medical checkups were recruited from Tianjin Medical University General Hospital. Participants were categorized into four groups according to their BMI levels and metabolically healthy status: metabolically healthy normal weight (MHNW), metabolically healthy overweight or obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight or obese (MUO). Blood samples (including serum uric acid) were collected from participants after an overnight fast. NAFLD was diagnosed based on abdominal ultrasonography scanning. Data were analyzed using logistic regression models and the interaction effect model.ResultsThe prevalence of NAFLD in MHNW, MHO, MUNW, and MUO groups was 9.9% (7.9–12.0%), 42.8% (39.5–46.1%), 36.5% (31.2–41.9%), and 69.7% (66.8–72.6%), respectively. In multi-adjusted logistic models, the ORs (95% CIs) of NAFLD were 5.32 (4.01–7.04) for participants with MHO, 4.51 (3.17–6.40) for those with MUNW, and 13.68 (10.23–18.30) for those with MUO compared to those with MHNW. In the stratified analysis by uric acid levels, the prevalence of NAFLD was significantly higher in participants with MHO, MUNW, and MUO in the hyperuricemia group than those in the normal uric acid group, and the interaction effect of metabolic phenotypes and uric acid on NAFLD was statistical significant (P < 0.05).ConclusionsMHO, MUNW, and MUO were associated with higher prevalence of NAFLD. Serum uric acid levels may modify the association between metabolically phenotypes and NAFLD.

Implementation of Shared Decision-Making Within Internet Hospitals in China Based on Patients’ Needs: Feasibility Study and Content Analysis

Internet hospitals are developing rapidly in China, and their convenient and efficient medical services are being increasingly recognized by patients. Many hospitals have set up their own internet hospitals to provide web-based medical services. Tianjin Medical University General Hospital has established a multidisciplinary and comprehensive internet hospital to provide diversified medical services according to the needs of patients. A way to further improve web-based medical services is by examining how shared decision-making (SDM) can be carried out in internet hospital diagnosis and treatment services, thereby improving patients' medical experience. The aim of this study was to analyze the feasibility of implementing doctor-patient SDM in internet hospital diagnosis and treatment services based on patients' needs in China. In this study, the medical data of 10 representative departments in the internet hospital of Tianjin Medical University General Hospital from January 1 to January 31, 2022, were extracted as a whole; 25,266 cases were selected. After excluding 2056 cases with incomplete information, 23,210 cases were finally included in this study. A chi-square test was performed to analyze the characteristics and medical service needs of internet hospital patients in order to identify the strengths of SDM in internet hospitals. The internet hospital patients from 10 clinical departments were significantly different in terms of gender (χ29=3425.6; P<.001), age (χ236=27,375.8; P<.001), mode of payment (χ29=3501.1; P<.001), geographic distribution (χ29=347.2; P<.001), and duration of illness (χ236=2863.3; P<.001). Patient medical needs included drug prescriptions, examination prescriptions, medical record explanations, drug use instructions, prehospitalization preparations, further consultations with doctors (unspecified purpose), treatment plan consultations, initial diagnoses based on symptoms, and follow-up consultations after discharge. The medical needs of the patients in different clinical departments were significantly different (χ272=8465.5; P<.001). Our study provides a practical and theoretical basis for the feasibility of doctor-patient SDM in internet hospitals and offers some implementation strategies. We focus on the application of SDM in web-based diagnosis and treatment in internet hospitals rather than on a disease or a disease management software. The medical service needs of different patient groups can be effectively obtained from an internet hospital, which provides the practical conditions for the promotion of doctor-patient SDM. Our findings show that the internet hospital platform expands the scope of SDM and is a new way for the large-scale application of doctor-patient SDM.

A nomogram to predict the risk of colorectal anastomotic leakage combining inflammatory-nutritional and abdominal aorta calcium index.

Anastomotic leakage is a serious complication after colorectal cancer surgery, which affects the quality of life and the prognosis. This study aims to create a novel nomogram to predict the risk of anastomotic leakage for patients with colorectal cancer based on the preoperative inflammatory-nutritional index and abdominal aorta calcium index. 292 patients at Tianjin Medical University General Hospital (Tianjin, China) from January 2018 to October 2021 who underwent colorectal cancer surgery with a primary anastomosis were retrospectively reviewed. A nomogram was constructed based on the results of multivariate logistic regression model. The calibration curves and receiver operating characteristic curves were used to verify the efficacy of the nomogram. Univariate and multivariate analyses showed that tumor location (P = 0.002), preoperative albumin (P = 0.006), preoperative lymphocyte (P = 0.035), preoperative neutrophil to lymphocyte ratio (P = 0.024), and superior mesenteric artery calcium volumes score (P = 0.004) were identified as the independent risk factors for postoperative anastomotic leakage in patients with colorectal carcinoma. A nomogram was constructed based on the results of the multivariate analysis, and the C-index of the calibration curves was 0.913 (95%CI: 0.870-0.957) in the training cohort and 0.840 (95%CI: 0.753-0.927) in the validation cohort. The nomogram, combining basic variables, inflammatory-nutritional index and abdominal aorta calcium index, could effectively predict the possibility of postoperative anastomotic leakage for patients with colorectal cancer, which could guide surgeons to carry out the appropriate treatment for the prevention of anastomotic leakage.

Influence of Anxiety and Depression on the Symptoms of Achalasia Patients: A Retrospective Cohort Study in China during COVID-19

Background: Idiopathic achalasia (AC) may be affected by anxiety and/or depression; however, reliable evidence is still lacking. The present retrospective cohort study aimed to explore the influence of psycho-mental factors on the severity of AC. Methods: All patients in the AC database of the Tianjin Medical University General Hospital from 2012 to 2020 were divided into two subgroups, intervention (n = 202) and medication (n = 84), according to previous treatments. Healthy people (n = 300) who underwent gastrointestinal endoscopy comprised the control group. The severity of symptoms and the anxiety and depression score of AC patients and controls were monitored by telephone and compared before and during COVID-19. In addition, the factors of AC symptoms during the COVID-19 were discussed by multiple linear regression. Results: During COVID-19, the anxiety and depression levels of AC patients and healthy individuals were deteriorated. For AC patients, before and after COVID-19, symptoms, anxiety, and depression scores in the medication group were more serious than those in the intervention group. Furthermore, previous therapy, depression, and gender were found to be significantly related to the severity of AC symptoms during COVID-19. Conclusions: The outbreak of COVID-19 made AC patients and healthy people anxious and depressed. Depression rather than anxiety might worsen the AC symptoms. Interventional therapy might protect AC patients against psychological abnormalities during COVID-19.

Fecal calprotectin as an indicator in risk stratification of pouchitis following ileal pouch–anal anastomosis for ulcerative colitis

Background Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis. Patients and methods This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups. Results Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (n = 40) and pouchitis group (n = 26). The correlation coefficient between the FC concentration and the PDAI score was 0.651 (p < 0.001). Receiver operating characteristic analysis showed that the FC cut-off value for predicting pouchitis was 579.60 μg/g (area under the curve, 0.938). The patients were then divided into three subgroups according to their PDAI score (0–2, 3–6, and ≥7), and significant differences in the FC concentration were found among the three subgroups. The best FC cut-off value for predicting a high risk of pouchitis (PDAI score of 3–6) was 143.25 μg/g (area under the curve, 0.876). Conclusions FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25–579.60 μg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients. KEY MESSAGES Fecal calprotectin can be used to quantify pouch inflammation. Fecal calprotectin can be used to predict a high risk of pouchitis.

Prognostic value and immunological roles of GPX3 in gastric cancer.

Objective: The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. Methods: The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. Results: A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Conclusions: Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.

Advancing Microbe Detection for Lower Respiratory Tract Infection Diagnosis and Management with Metagenomic Next-Generation Sequencing.

Due to limitations of traditional microbiological methods and the presence of the oropharyngeal normal flora, there are still many pathogens that cause lower respiratory tract infections (LRTIs) cannot be detected. Metagenomic next-generation sequencing (mNGS) has the potential capacity to solve this problem. This retrospective study successively reviewed 77 patients with LRTI and 29 patients without LRTI admitted to Tianjin Medical University General Hospital, China from August 2020 to June 2021. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected adopting mNGS and traditional microbiological assays. The diagnostic performance of pathogens was compared between mNGS and BALF culture. The value of mNGS for aetiological and clinical impact investigation in LRTI was also evaluated. Among 77 patients with LRTI, 22.1%, 40.3%, and 65.0% of cases were detected as definite or probable pathogens by culture, all conventional microbiological tests, and mNGS, respectively. Using the final diagnosis as a gold standard, mNGS exhibited a sensitivity of 76.6% (95% confidence interval [CI], 65.6-85.5%), which was considerably superior to that of BALF culture (76.6% vs 18.2%; P < 0.01); specificity of 79.3% (95% CI, 60.3-92.0%), which was similar (79.3% vs 89.7%; P = 0.38); positive-predictive value of 90.8% (95% CI, 81.0-96.5%), and negative-predictive value of 56.1% (95% CI, 39.7-71.5%). According to our data, mNGS identified potential microorganisms in 66.7% (42/63) of culture-negative samples. Among 59 patients with pathogens identified by mNGS, conventional microbiological methods confirmed pathogenic infections in less than half (28/59) cases. Within the 77 patients, 34 (44.2%) patients received pathogen-directed therapy, 7 (9.1%) patients underwent antibiotic adjustment, and 3 (3.9%) patients stopped using antibiotics due to mNGS results. mNGS exhibits high accuracy in diagnosing LRTI, and combine with traditional microbiological tests, causative pathogens can be detected in approximately 70.0% of cases, thus yields a positive effect on antibiotic application.

Cancer associated autoantibodies in idiopathic inflammatory myopathies: A retrospective cohort from a single center in China

ObjectivesIdiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs. MethodsThis retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0. ResultsThe results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35–22.64) and 22.31 (4.32–115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. ConclusionsAnti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies. Anti-TIF1-γ antibody positive CAM was a subset that comprised about half of CAM entities and had the characteristic of poor prognosis.

Clinical value of regional lymph node sorting in gastric cancer.

Increasing evidence have shown that regional lymph node metastasis is a critical prognostic factor in gastric cancer (GC). In addition, lymph node dissection is a key factor in determining the appropriate treatment for GC. However, the association between the number of positive lymph nodes and area of lymph node metastasis in GC remains unclear. To investigate the clinical value of regional lymph node sorting after radical gastrectomy for GC. This study included 661 patients with GC who underwent radical gastrectomy at Tianjin Medical University General Hospital between January 2012 and June 2020. The patients were divided into regional sorting and non-sorting groups. Clinicopathological data were collected and retrospectively reviewed to determine the differences in the total number of lymph nodes and number of positive lymph nodes between the groups. Independent sample t-tests were used for intergroup comparisons. Continuous variables that did not conform to a normal distribution were expressed as median (interquartile range), and the Mann-Whitney U test was used for inter-group comparisons. There were no significant differences between the groups in terms of the surgical method, tumor site, immersion depth, and degree of differentiation. The total number of lymph nodes was significantly higher in the regional sorting group (n = 324) than in the non-sorting group (n = 337) (32.5 vs 21.2, P < 0.001). There was no significant difference in the number of positive lymph nodes between the two groups. A total of 212 patients with GC had lymph node metastasis in the lymph node regional sorting group, including 89 (41.98%) cases in the first dissection station and 123 (58.02 %) cases in the second dissection station. Binary and multivariate logistic regression results showed that the number of positive lymph nodes (P < 0.001) was an independent risk factor for lymph node metastases at the second dissection station. Regional sorting of lymph nodes after radical gastrectomy may increase the number of detected lymph nodes, thereby improving the reliability and accuracy of lymph node staging in clinical practice.

Potential blood biomarkers for chronic traumatic encephalopathy: The multi-omics landscape of an observational cohort.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, which is susceptible in elderly people with declined mobility, athletes of full contact sports, military personnel and victims of domestic violence. It has been pathologically diagnosed in brain donors with a history of repetitive mild traumatic brain injury (rmTBI), but cannot be clinically diagnosed for a long time. By the continuous efforts by neuropathologists, neurologists and neuroscientists in recent 10 years, an expert consensus for the diagnostic framework of CTE was proposed in 2021 funded by the National Institute of Neurological Disorders and Stroke. The new consensus contributes to facilitating research in the field. However, it still needs to incorporate in vivo biomarkers to further refine and validate the clinical diagnostic criteria. From this, a single-center, observational cohort study has been being conducted by Tianjin Medical University General Hospital since 2021. As a pilot study of this clinical trial, the present research recruited 12 pairs of gender- and age-matched rmTBI patients with healthy subjects. Their blood samples were collected for exosome isolation, and multi-omics screening to explore potential diagnostic biomarkers in blood and its exosomes. The expression level of CHL1 protein, KIF2A mRNA, LIN7C mRNA, miR-297, and miR-1183 in serum and exosomes were found to be differentially expressed between groups. Besides, serum and exosomal CHL1, KIF2A, and miR-1183, as well as exosomal miR-297 were further verified as potential biomarkers for CTE by low-throughput assays. They are expected to contribute to establishing a novel set of CTE diagnostic signatures with classic neurodegenerative indicators in our future study, thereby updating the consensus diagnostic criteria for CTE by incorporating new evidence of the in vivo biomarkers.

Long-term efficacy of low-dose rituximab treatment in patients with primary membranous nephropathy

Objective: To explore the long-term efficacy of low-dose rituximab (RTX) treatment in patients with primary membranous nephropathy (PMN). Methods: Patients with biopsy-proven PMN who received low-dose RTX as initial or second-line regimen from August 2018 to May 2020 in the Department of Nephrology, Tianjin Medical University General Hospital were respectively enrolled. The clinical parameters of patients were urinary protein>3.5 g/24 h, serum albumin<30 g/L and estimated glomerular filtration rate (eGFR)>20 ml·min-1·(1.73 m2)-1. The treatment response of patients with PMN was observed during follow-up, and the remission rate of patients with urinary protein<8 g/24 h or ≥8 g/24 h, anti-PLA2R antibody<150 RU/ml or ≥150 RU/ml, eGFR≥ 60 ml·min-1·(1.73 m2)-1 or<60 ml·min-1·(1.73 m2)-1 were analyzed, respectively. Results: A total of 40 patients were enrolled, including 26 males and 14 females, aged (53±15) years. There were 14 patients received RTX as initial treatment and 26 patients as second-line therapy. The total median dose of RTX in the first course was 800 (425, 1 075) mg. The overall remission rate at the 1st, 3rd, 6th, 12th and 24th months were 12.5% (5/40), 17.5% (7/40), 47.5% (19/40), 57.5% (23/40), 60% (24/40), respectively. The median overall response time was 6.0 (3.0, 7.5) months. Two cases relapsed. Patients with remission (n=24) had a higher level of baseline eGFR [(93.9±28.0) vs (62.4±28.1) ml·min-1·(1.73 m2)-1, P=0.001), and a lower level of both urinary protein [5.9 (5.0, 6.5) vs 11.7 (8.6, 15.5) g/24 h, P<0.001] and anti-PLA2R antibody level [73 (29, 132) vs 453 (182, 950) RU/ml, P=0.004] than those without remission (n=16) 24 month after treatment. There was no statistically significant difference in the remission rate between initial and second-line treatment (P=0.101). Moreover, patients had a higher remission rate in urinary protein<8 g/24 h group (21/26 vs 3/14, P<0.001), anti-PLA2R antibody<150 RU/ml group (16/19 vs 5/16, P=0.002) and eGFR ≥ 60 ml·min-1·(1.73 m2)-1 group (22/29 vs 2/11, P=0.003). Conclusions: Low-dose RTX treatment in PMN is effective during long-term follow-up, and has a lower recurrence rate. The results also suggest that it is more suitable for patients with baseline urinary protein<8 g/24 h, anti-PLA2R antibody<150 RU/ml and eGFR≥ 60 ml·min-1·(1.73 m2)-1.

Analysis of the clinical features of antisynthetase syndrome: a retrospective cohort study in China.

To summarize the clinical, serological, and radiological characteristics of anti-synthetase syndrome (ASS) patients with different anti-aminoacyl-tRNA synthase antibody. Retrospective analysis was performed based on the clinical data of 88 patients diagnosed with ASS in Tianjin Medical University General Hospital from January 2015 to December 2020. The clinical data included general conditions, serological indexes, high-resolution CT (HRCT) characteristics, and pulmonary function manifestations. Among the 88 patients, there were 17 males and 71 females. The anti-synthetase antibodies included anti-Jo-1 (n = 42), anti-PL-7 (n = 14), anti-PL-12 (n = 9), anti-EJ (n = 20), and anti-OJ (n = 3) antibodies. The most common clinical manifestations of ASS patients were interstitial lung disease (ILD) (90%, 79/88), followed by myositis (79.5%, 70/88), arthritis (50%, 44/88), and rash (50%, 44/88). The frequency of arthritis in the anti-Jo-1 antibody-positive group was higher than that of the anti-PL-7 and anti-EJ antibody groups (P = 0.004, P = 0.002, respectively). The frequency of Gottron's sign in the anti-PL-7 antibody positive group was higher than that of the anti-Jo-1 and anti-PL-12 antibody-positive groups (P = 0.006, P = 0.04). Isolated arthritis was the most frequent initial symptoms in anti-Jo-1 antibody-positive group (47.6%, 20/42), while isolated ILD was most frequent in patients with anti-EJ antibody (50%, 10/20), and isolated myositis in patients carrying anti-OJ (66.7%, 2/3). There were only 32 cases (36.4%) with the typical clinical triad (myositis, arthritis, ILD). In our cohort, 79 patients (90%) were complicated with ILD. Meanwhile, 7 out of 79 cases were classified into rapid progressive group with 6 cases (85.7%) carrying anti-Ro-52 antibody. The probability of reticular and honeycombing shadow in HRCT of patients with anti-EJ antibody positive was higher than that of other groups (P < 0.05). ILD, myositis, and arthritis were the most common clinical manifestations in patients with ASS. Different antibody-positive patients have different initial symptoms. Patients with isolated arthritis, myositis, and ILD should be vigilant of ASS. The complication of anti-Ro-52 antibody in ASS patients was associated with rapidly progressive pulmonary interstitial disease. Patients with positive anti-EJ antibodies tend to have ILD as the first symptom, and with high occurrence of ILD, the HRCT showed more serious patterns, suggesting the correlation between anti-EJ antibodies and ILD. Key Points • Analyzing specific clinical manifestations in ASS patients with different ARS antibodies can raise awareness of the disease and reduce misdiagnosis. • Anti-EJ antibodies were correlated with ILD. • Anti-Ro-52 antibodies may correlate with RP-ILD in ASS patients.

Acute Gaseous Air Pollution Exposure and Hospitalizations for Acute Ischemic Stroke: A Time-Series Analysis in Tianjin, China.

Background: Stroke has always been an important problem troubling human health. Short-term exposure to air pollutants is associated with increased hospital admissions. The rise of pollutants such as O3 has caused a huge social and economic burden. This study aims to explore the relationship between short-term exposure to ambient gaseous pollutants and daily hospitalizations for ischemic stroke, utilizing a four-year time-series study in Tianjin. Methods: Collecting the data of gaseous pollutants (NO2, SO2, CO, O3), meteorological data (including daily average temperature and relative humidity) and the number of hospitalizations due to ischemic stroke in Tianjin Medical University General Hospital from 2013 to 2016. Poisson regression generalized additive model with single-day and multi-day moving average lag structure was used to estimate adverse effects of gaseous pollutants on daily hospitalizations. Subgroup analysis was performed to detect modification effect by gender and age. Results: In total, there were 9081 ischemic stroke hospitalizations. After controlling for the meteorological factors in the same period, no significant findings were found with the increase of NO2, SO2, CO and O3 concentrations at most of the time in the single-pollutant model. Similarly, in the stratified analysis, no associations between gaseous pollutants and ischemic stroke were observed in this study. Conclusions: Short-term exposure to NO2, SO2, CO and O3 was not distinctly associated with daily hospitalizations for ischemic stroke in Tianjin. Multicenter studies in the future are warranted to explore the associations between gaseous pollution exposure and ischemic stroke.

High cerebrospinal fluid lactate concentration at 48 h of hospital admission predicts poor outcomes in patients with tuberculous meningitis: A multicenter retrospective cohort study.

ObjectiveThis study aimed to analyze the cerebrospinal fluid (CSF) parameters affecting the outcomes of patients with tuberculous meningitis (TBM).MethodsThis is a multi-center, retrospective, cohort study involving 81 patients who were diagnosed with TBM and treated in Haihe Clinical College of Tianjin Medical University, Tianjin Medical University General Hospital, and General Hospital of Air Force PLA from January 2016 to December 2019. Baseline data, Glasgow Coma Scale (GCS) score, and clinical presentations of all patients were collected at admission. CSF samples were collected at 48 h, 1, 2, and 3 weeks after admission. CSF lactate, adenosine deaminase, chloride, protein, glucose levels and intracranial pressure were measured. After a follow-up of 16.14 ± 3.03 months, all patients were assessed using the modified Rankin Scale (mRS) and divided into good (mRS scores of 0–2 points) and poor outcome groups (mRS scores of 3–6 points). The differences in patients' baseline data, GCS score, clinical presentations, and levels of CSF parameters detected at 48 h, 1, 2, and 3 weeks after admission between two groups were compared. Statistically significant variables were added to the binary logistic regression model to identify the factors impacting the outcomes of patients with TBM. Receiver operating characteristic (ROC) curve was used to assess the predictive ability of the model.ResultsThe CSF lactate level exhibited a decreasing trend within 3 weeks of admission in the two groups. For the within-group comparison, statistically significant differences in the lactate level was found in both groups between four different time points. A binary logistic regression model revealed that CSF lactate level at 48 h after admission, age, and GSC score on admission were independently associated with the outcomes of patients with TBM. ROC curve analysis showed that the area under the ROC curve (AUC) was 0.786 for the CSF lactate level (48 h), 0.814 for GCS score, and 0.764 for age.ConclusionHigh CSF lactate level at 48 h after admission is one of the important factors for poor outcomes in patients with TBM.

Association of CDH1, FANCB and APC Gene Polymorphisms with Lung Cancer Susceptibility in Chinese Population

背景与目的肺癌是全球癌症相关死亡的主要原因，单核苷酸多态性（single nucleotide polymorphism, SNP）是导致肺癌发生的重要因素之一，但其机制仍未阐明。本研究拟探讨CDH1、FANCB、APC基因SNP与肺癌遗传易感性的关系。方法采用病例对照研究方法，收集来自天津医科大学总医院肺部肿瘤外科270例肺癌病例，同时收集445名健康志愿者的血液样本作为对照，并提取基因组DNA，使用TaqmanⓇ SNP基因分型试剂盒进行基因分型，分析CDH1基因rs201141645、FANCB基因rs754552650和APC基因rs149353082三个SNPs位点在中国人群中的分布。采用卡方检验和Logistic回归分析探索不同基因型与肺癌发病风险之间的关系。结果FANCB基因rs754552650位点的AA、A/G和GG基因型的分布频率在对照组中分别为27.2%、52.6%和20.2%。AA和A/G基因型分布频率在病例组中分别为93.7%、6.3%，未检测到GG基因型。FANCB基因的rs754552650位点的A/G基因型在病例组和对照组中存在显著差异。携带者患肺癌的风险明显降低（OR=0.035, 95%CI: 0.020-0.062, P < 0.001）。CDH1基因rs201141645 A/C和CC基因型仅存在于对照组中。此外，在病例组中仅发现1个样本存在APC基因rs149353082 C/G基因型。结论在中国人群中，FANCB基因rs754552650 A/G基因型携带者患肺癌的风险明显降低。

Clinical application value of peripheral blood metagenomic next-generation sequencing test for patients with hematological diseases accompanied by fever

Objective: To investigate the clinical application value of peripheral blood metagenomic next-generation sequencing (mNGS) test for patients with hematological diseases accompanied by fever. Methods: The blood mNGS results and clinical data of inpatients with hematological diseases accompanied by fever treated in the Hematology Department of Tianjin Medical University General Hospital in March 2020 to June 2021were retrospectively analyzed. A total of 90 patients with 98 cases of specimens were included. The pathogen distribution characteristics and mNGS test performance were analyzed. Results: The positive rate of peripheral blood mNGS was significantly higher than that of traditional examination (68.37% vs 37.76%, P<0.001) and blood culture (68.37% vs 9.18%, P<0.001) . Viral, bacterial, and fungal infections accounted for 38.81%, 14.93%, and 2.99% in patients with single-pathogen infections, respectively. Polymicrobial infections accounted for 43.28%, in which viral and bacterial coinfections were the most common type (25.37%) . There were 55 virus-positive cases (82.09%) , 30 bacteria-positive cases (44.78%) , and 14 fungus-positive cases (20.90%) . The clinical approval rate of peripheral blood mNGS was 64.63% (63/98) . The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of peripheral blood mNGS were 75.68%, 36.07%, 41.79%, and 70.97%, respectively, and the overall consistency rate with traditional examination was 51.02%. Of the 22 pulmonary infection cases with no detectable pathogens by conventional tests, the pathogens were identified by peripheral blood mNGS in 14 cases, 10 of which were clinically approved. Conclusion: The positive rate of peripheral blood mNGS was significantly higher than that of blood culture and traditional laboratory examination. Peripheral blood mNGS had a high clinical recognition rate, sensitivity, and NPV in the detection of pathogens in patients with hematological diseases accompanied by fever.

Risk stratification of patients with acute respiratory distress syndrome complicated with sepsis using lactate trajectories

BackgroundNo consensus has been reached on an optimal blood lactate evaluation system although several approaches have been reported in the literature in recent years. A group-based trajectory modeling (GBTM) method could better stratify patients with acute respiratory distress syndrome (ARDS) complicated with sepsis in the intensive care unit (ICU).Patients and methods760 patients from the comprehensive ICU of Tianjin Medical University General Hospital with ARDS complicated with sepsis were eligible for analysis. Serial serum lactate levels were measured within 48 h of admission. In addition to the GBTM lactate groups, the initial lactate, peak lactate level, the area under the curve of serial lactate (lactate AUC), and lactate clearance were also considered for comparison. The short- and long-term outcomes were the 30- and 90-day mortality, respectively.ResultsThree lactate groups were identified based on GBTM, with group 3 exhibiting the worse short- [hazard ratio (HR) for 30-day mortality: 2.96, 95% confidence interval (CI) 1.79–4.87, P < 0.001] and long term (HR for 90-day mortality: 3.49, 95% CI 2.06–5.89, P < 0.001) outcomes followed by group 2 (HR for 30-day mortality: 2.05, 95% CI 1.48–2.84, P < 0.001 and HR for 90-day mortality: 1.99, 95% CI 1.48–2.67, P < 0.001). GBTM lactate groups exhibited significantly improved diagnostic performance of initial lactate + SOFA scores/APACHE II scores models. Based on the multivariable fractional polynomial interaction (MFPI) approach, GBTM lactate groups could better differentiate high-risk patients than the initial lactate groups in short- and long-term outcomes.ConclusionsTo the best of our knowledge, this is the first report that GBTM-based serial blood lactate evaluations significantly improve the diagnostic capacity of traditional critical care evaluation systems and bring many advantages over previously documented lactate evaluation systems.

Effect of a combination of Xuebijing and thymosin α1 on patients with severe pneumonia complicated with sepsis, and its influence on serum inflammatory factors

Purpose: To investigate the influence of a combination of Xuebijing and thymosin α1 on acute and septic bronchopneumonia (ASB) patients, and the effect of the treatment on inflammation.&#x0D; Methods: Eighty-one (81) ASB patients admitted to Tianjin Medical University General Hospital, Tianjin China from January 2015 to July 2019 were enrolled in the study. The patients were assigned to control group (n = 41) and a study group (n = 40). The control patients were treated with Xuebijing injection, i.v., while the study group received a combination of Xuebijing injection and thymosin α1 via the subcutaneous route. Patients’ body temperature, heartbeat, white blood cell count, as well as other parameters, including blood gas indices, serum concentrations of IL-6, TNF-α and C-reactive protein (CRP), as well as well as blood gas indices were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial clearance and therapeutic effectiveness were evaluated pre- and post-treatment.&#x0D; Results: Post-therapy basal temperature, breathing, heartbeat, number of white blood cells and other indices decreased in study patients, relative to control (p &lt; 0.05). Moreover, the levels of hydrogen ion concentration (pH) and arterial carbon dioxide partial pressure (PaCO2) were significantly lower in study group than in control group (p &lt; 0.05). Patients in the study group had lower serum levels of IL-6, TNF-α and CRP, when compared to control group, while bacterial load was significantly reduced in study subjects, relative to controls (p &lt; 0.05).&#x0D; Conclusion: Combined use of thymosin α1 and Xuebijing is significantly effective in the management of patients suffering from ASB. The combination therapy also improves the hemorheological status of patients. Thus, it is a potential therapeutic strategy for ASB.&#x0D; Keywords: Acute bronchopneumonia; Xuebijing; Thymosin α1; Septicemia; Inflammation