[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[The clinical application of targeted next-generation sequencing and metagenomics next-generation sequencing in pathogenic microorganism detection].

Infectious diseases seriously threaten human health. The early detection of the causative organism and antibiotic resistance genes of infection remains a major clinical challenge. Next-generation sequencing has been widely used in diagnosing infectious diseases. Cheaper and faster targeted next-generation sequencing technology is progressively being used in clinical practice. However, the awareness among clinicians about the clinical utility of this technology is limited. The article presents the theoretical background, advantages and disadvantages, clinical applications of targeted next-generation sequencing, and its contrasts with metagenomics next-generation sequencing. It provides a reference for clinicians to select laboratory methods for identifying pathogens in clinical practice.

[Analysis on the imported Coronavirus Disease 2019 related cluster epidemic in rural areas of Chengdu].

An epidemiological investigation was carried out on a local cluster of outbreak caused by imported cases of Coronavirus Disease 2019 (COVID-19) in rural areas of Chengdu in December 2020, to find out the source of infection and the chain of transmission. According to Prevention and Control Protocol for COVID-19 (Version 7), field epidemiological investigation was adopted, combined with big data technology, video image investigation, gene sequencing and other methods to carry out investigation into COVID-19 cases and infections source tracing, analyze the epidemiological association, and map the chain of transmission. From December 7 to 17, 2020, 13 local COVID-19 confirmed cases and 1 asymptomatic case were diagnosed in Chengdu, of which 12 cases (85.71%) had a history of residence and activity in the village courtyard of Taiping (TP), Pidu (P) District, Chengdu. From November 8, 2020 to November 28, 2020, a group of inbound people form Nepal were transferred to the designated entry personnel quarantine hotel of P District which was adjacent to the TP village. During quarantine, there were 5 cases who tested positive for COVID-19. Through gene sequencing alignment, genes of local cases and Nepalese imported cases from the same period are homologous, all belong to the lineage of L2.2.3 (B.1.36 according to Pangolin lineage typing method). According to the results of field epidemiological investigation and gene sequencing analysis, the index case was most likely infected by contact with household waste of quarantine site. Under the situation of normalization prevention and control of COVID-19, sentinel monitoring of fever clinics in primary medical institutions is the key to early detection of the epidemic. The multi-department joint epidemiological investigation and the application of gene technology are the core links of the investigation and traceability of modern infectious diseases. The allocation of public health resources in rural areas needs to be strengthened. We need to improve the capacity for early surveillance and early warning of the epidemic in rural areas.

[Comparison of different reconstruction procedures after distal gastrectomy in patients with gastric cancer].

Objective: To systematically compare the effect of Roux-en-Y with Billroth Ⅰ or Billroth Ⅱ in gastric cancer patients after distal gastrectomy by meta-analysis. Methods: Systematic search was conducted on the relevant electronic databases of Pubmed, Embase, Wanfang Database, CNKI and VIP from the established time to August 18, 2019. The randomized controlled trials about comparison of Roux-en-Y with Billroth Ⅰ or Billroth Ⅱ were strictly screened and analyzed by the software of Revman 5.3. Procedure and postoperative outcomes were analyzed, respectively. Results: A total of 783 relevant literatures were systematically retrieved, and 6 randomized controlled trials, including 954 patients, finally met the inclusion criteria after strict screening. The results of meta-analysis showed that operative time of Billroth Ⅰ was significantly shorter than that of Roux-en-Y (MD=-37.60, 95%CI:-50.79--24.40, P<0.001), intraoperative bleeding (MD=-21.64, 95%CI:-32.20--11.07, P<0.001) and the number of delayed gastric emptying (RR=0.52, 95%CI: 0.31-0.86, P=0.01) of Billroth Ⅰ were both significantly less than those of Roux-en-Y, while bile reflux (RR=8.17, 95%CI: 2.21-31.53, P=0.002) and residual gastritis (RR=1.75, 95%CI:1.43-2.14, P<0.000 01) of Billroth Ⅰ were both significantly higher than those of Roux-en-Y, other outcomes showed no significant difference. Compared with Roux-en-Y, operative time of Billroth Ⅱ was significantly shorter (MD=-19.73, 95%CI:-32.82--6.64, P=0.003), while bile reflux (RR=17.63, 95%CI: 4.50-69.02, P<0.001), residual gastritis (RR=1.94, 95%CI:1.15-3.26, P=0.01) and reflux esophagitis (RR=3.13, 95%CI: 1.31-7.45, P=0.01) of Billroth Ⅱ were all significantly higher, and there was no significant difference in other outcomes. Conclusion: Compared with Billroth Ⅰ and Billroth Ⅱ, the operation time of Roux-en-Y in gastric cancer patients undergoing distal gastrectomy is longer, but the incidences of bile reflux and residual gastritis are both lower, and the postoperative quality of life seems better.

[Effect of omeprazole on plasma concentration and adverse reactions of capecitabine in patients with colon cancer].

Objective: To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods: Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results: The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) µg/ml, without significant difference of (123.09±56.70) µg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05). Conclusion: The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.

[Application of adaptie statistical iterative reconstruction technology combined with low tube voltage in three phase enhanced low dose liver scanning].

Objective: To explore the application value of adaptive statistical iterative reconstruction (ASIR) combined with low tube voltage in three-stage enhanced low-dose scan of liver. Methods: From March 2017 to November 2017, two groups which each group included 50 patients were randomly selected at the Second Affiliated Hospital of Harbin Medical University with different stages of arterial phase, delayed phase and portal vein scanning. GE Discovery CT 750 HD Liver CT Ⅲ was used during enhanced scanning. A total of 100 patients included 56 males and 44 females, aged 27-73 years old and 42 patients with hepatocellular carcinoma, 44 patients with hepatic hemangioma, and 14 patients with other diseases. The arterial and delayed period of group A patients were scanned with a low dose of 100 kV+ASIR, and the portal vein phase was conventional. Dosage scanning was 120 kV+FPP; the arterial and delayed period of group B was normal dose scanning, 120 kV+FPP, and the portal vein phase was low dose scanning, 100 kV+ASIR. At the same time, FBP reconstruction was used for all low-dose scanning phases to obtain low-dose images under normal reconstruction mode. The objective evaluation index of image quality was analyzed by completely randomized design analysis of variance, and Dunnett-t test was used to compare the two groups. For the subjective evaluation part, the rank sum test of multiple groups was used. Results: ASIR combined with low tube voltage enhanced low dose scanning in the third phase of the liver, and the radiation dose decreased by 37% in the low dose group compared with the normal dose group. There was no statistically significant difference between the low dose group (100 kV+ASIR) and the normal dose group (120 kV+FPP) in subjective image quality evaluation (P>0.05); objective evaluation of image quality except for low dose(100 kV+ASIR) portal stage noise slightly worse than conventional dose group (120 kV+FBP) (low dose 10.86±1.98, conventional dose 9.40±2.12, P<0.05), the other indexes in each period were superior or indifferent to the normal dose group. Conclusion: ASIR technique combined with low tube voltage can be used in the third phase of liver enhanced low-dose scanning and the image quality is improved.

[Microcystic, elongated and fragmented invasion pattern in endometrial carcinoma: the clinicopathology analysis].

Objective: To assess the clinical value for the clinicopathological features of microcystic elongated and fragmented (MELF) invasion in endometrial carcinoma (EEC) . Methods: The clinicopathological data of 108 cases of endometrial carcinoma with total hysterectomy, bilateral adnexectomy, and pelvic dissection were retrospectively analysis in Peking University People's Hospital from April 2015 to October 2016. Twenty-five patients with endometrial carcinoma showing MELF invasion pattern were collected. We analyzed retrospectively the association of MELF pattern invasion with clinical pathology data and prognosis of the patients, partial immunohistochemical staining was implemented. MELF invasion was a special invasion pattern and characterized by microcystic, elongated, fragmented (composed of cluster cells) gland in muscular layer. Results: The incidence rate was 23.1% (25/108). These patients mean age was (59.3±10.9) years old. Four cases were premenopausal, and 21 were postmenopausal. Abnormal vaginal bleeding was the main clinical presentation. The lesions tend to appear adjacent to the tumor body. Sometimes, it may be appears away from the tumor body in the deep muscle layer.Lymph node metastasis were present in 5 cases (20%, 5/25). Thirteen cases (52%, 13/25) of them demonstrated lymph vascular space involvement (LVSI). The immunohischemical expression of ER,PR, Ki-67 and galectin-3 showing MELF invasion pattern were weaker than no showing MELF invasion pattern endometrial carcinoma, cktokeratin (CK) was showed diffuse strong positive expression, E-cadherin was moderately positive expression. All 25 cases were followed up for (23.2±5.9) months (14-33 months) after the therapy with no recurrence on metastasis. Conclusions: MELF invasion pattern is a special invasion pattern in low-grade EEC. The incidence of LVSI and lymph node metastasis rate in endometrial carcinoma with MELF invasion are significantly increased. The prognosis of MELF invasion pattern may be poor.

[Correlation between N-terminal probrainnatriuretic peptide and prognosis of acute exacerbations of chronic obstructive pulmonary disease].

Objective: To evaluate the correlation between N-terminal probrainnatriuretic peptide (NT-proBNP) and the prognosis of death in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease(COPD). Methods: A cohort study of 169 patients with acute exacerbations COPD. According to the age and NT-proBNP value measured on admission, cases were divided into 3 groups. The risk ratio of mortality among the three group were analyzed. Results: Thirty-two patients died within 1 year. There are 93 cases in group A (NT-proBNP < 300 ng/L), 45 cases in group B (aged 75 and below with NT-proBNP 300-900 ng/L, older than 75 with NT-proBNP 300-1 800 ng/L), 31 cases in group C (aged 75 and below with NT-proBNP>900 ng/L, older than 75 with NT-proBNP>1 800 ng/L); The in-hospital mortalities were 3.2%, 11.1% and 32.3%respectively, and mortalities within a year were 5.4%, 17.8% and 61.3% . The risk ratio (RR) and 95%CI for dying in hospital of group C to group A and B were 10.00 (3.61-56.50) and 2.90 (1.15-12.60), RR and 95%CI for dying within 1 years after hospitalization were 11.40 (8.78-88.46) and 3.45 (2.56-20.97, P<0.05). Conclusion: The NT-proBNP values measured at admission were associated with the short-term and long-term prognosis of patients with AECOPD.

[Respiratory virus infections and inflammatory cytokines in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To investigate the characteristics of respiratory viral infections, and correlation between inflammatory cytokines and respiratory virus infections in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). Methods: A prospective cohort of patients with acute exacerbations of COPD was enrolled. The sputum of all patients were collected, and 15 respiratory viruses were detected using multi-channel real-time fluorescence quantitative PCR. The clinical characteristics associated with viral infections were analyzed. The peripheral blood of the patients was collected and cytokines including IL-6, IL-8, RANTES, IP-10, sIL-2R, IFN-γ, TNF-α in the serum were detected by ELISA. Association of these cytokines with respiratory viral infections was evaluated and a discriminant model was established. Results: A total of 99 patients with acute exacerbations of COPD were enrolled in this study. Thirty-four cases (34.3%, 34/99) were positive for viral detection. Among them, the positive rate of influenza A virus was the highest (38.2%, 13/34), followed by rhinovirus (35.3%, 12/34). Multifactor logistic regression analysis showed that, fever, COPD assessment test (CAT) score in stable stage, serum IP-10 and TNF-α levels were correlated with respiratory viral infections in patients with acute exacerbations of COPD. The levels of serum IP-10 and sIL-2R increased significantly in patients with influenza A virus. Conclusions: Respiratory viral infections were common in acute exacerbations of COPD. Influenza A virus and rhinovirus were the two most common viruses. Fever was a common symptom. Patients with severe respiratory symptoms at stable stage were susceptible to viral infection. Viral infection was associated with an increase in systemic inflammatory levels, most significantly in influenza virus infection. A discriminant model composed of fever, CAT score in stable stage, serum IP-10 and TNF-α levels can be used to predict respiratory viral infections in acute exacerbations of COPD.

[Analysis of the tibial baseplate coverage and symmetrical tibial prosthesis in primary total knee arthroplasty].

Objective: To investigate the tibial baseplate coverage with symmnetrical tibial prosthesis in primary total knee arthroplasty (TKA). Methods: From August 2014 to February 2015, 39 patients (39 knees) with varus knee osteoarthritis were retrospective reviewed in Department of Orthopaedics, Tianjin Xiqing Hospital. Nine males and 30 females; aged 50 to 78 years (67±6 year). 3D tibia models of the knee were built with Mimics 10.01 software, simulated TKA surgeries were performed. The morphology of the proximal tibia was measured, including the mediolateral (ML), anteroposterior (AP) and medial and lateral tibial plateau AP dimensions. 3D models of PFC Sigma tibial prosthesis were imported and the tibial coverage characters were analyzed. Results: The AP and ML dimensions of the tibial resection surface were (45.7± 3.4) mm, (71.7± 4.2) mm respectively, the plateau aspect ration ratio (AP/ML) was 63.8%±3.0%. The medial tibial plateau AP[(46.9± 3.3) mm]was significantly greater than the lateral side[(41.8±3.3) mm, P=0.000], the asymmetric ratio averaged 112.4%±6.9%. The medial tibial plateau, anteromedial, posteromedial, posterolateral unsatisfied coverage ratio were 33.3%, 76.9%, 20.5%, 33.3% respectively. There are 5 cases underhang and 3 cases overhang in the posteromedial side, whereas 1 case underhang and 12 cases overhang posterolateral, the overhang ratio was 30.8%. Posteromedial, posterolateral prosthesis coverage had linear positive correlation to the ipsilateral tibial plateau AP diameter. Conclusions: The medial AP diameter of tibial plateau is significantly lager than the lateral side in varus knee osteoarthritis patients. With symmetrical tibial baseplate placement in TKA, the prosthesis usually lead to medial tibial plateau anterior and posterior underhang and posterolateral overhang.

Sagnac interferometer hydrogen sensor based on panda fiber with Pt-loaded WO3/SiO2 coating.

A highly sensitive optical fiber Sagnac interferometer hydrogen sensor is proposed and demonstrated. The device is fabricated by inserting a segment of panda fiber coated with Pt-loaded WO3/SiO2 into a Sagnac interferometer loop. When Pt/WO3 film is exposed to hydrogen, the exothermic reaction raises the temperature of the panda fiber, resulting in the resonant wavelength shift of the interferometer, and the resonant dip obtained has a large extinction ratio of ∼25 dB and a narrow linewidth of 2.5 nm. Such a device responds fast to hydrogen, exhibits a high sensitivity of -7.877 nm/% (vol. %) within the range of 0%-1.0% and is robust, low cost, and easy to fabricate.

[A meta-analysis of perioperative hyperoxia for the surgical site infections in patients with general surgery].

OBJECTIVE: To systemically analyze the effect of perioperative hyperoxia for the surgical site infections in patients with general surgery. METHODS: Electronic databases consisting of Pubmed, Embase, Cochrane Library, Wanfang Database, CNKI and VIP were systemically searched from established time to November 18, 2015. The randomized controlled trials about perioperative high and low-concentration oxygen for the surgical site infections in patients with general surgery were screened strictly and analyzed by the software of Revman 5.3. The included trials were stratified according to the colorectal or non-colorectal surgery, the duration of oxygen inhalation and the kinds of mixed gas to perform subgroup analyses. Sensitivity analysis was conducted by removing the low-quality trials, etc. The outcome was the surgical site infections. RESULTS: There were 989 relevant articles were searched out. At last, 9 randomized controlled trials consisting of 3 281 patients were included. The 80% oxygen group and 30% oxygen group consists of 1 644 and 1 637 patients, respectively. The rates of surgical site infection were 15.1% (248/1 644) and 17.5% (286/1 637) in the two group. Heterogeneity existed between the included trials and random-effect model was used, the RR=0.80, 95%CI: 0.60-1.08, P=0.15. Therefore, statistically significant difference was not found for the surgical site infections in the general surgery between the perioperative high and low-concentration oxygen. However, the results of subgroup analyses showed that the perioperative hyperoxia decreaced the surgical site infections significant in the subgroups of colorectal surgery and intraoperative plus postoperative 6 h oxygen inhalation. CONCLUSIONS: Perioperative hyperoxia does not reduce surgical site infections in patients with general surgery. However, the results of two subgroup analyses (colorectal surgery and intraoperative plus postoperative 6 h oxygen inhalation trials) show a significantly benefit for perioperative hyperoxia in decreasing surgical site infections.

[Prostate biopsy results and clinicopathological characteristics of the 55 years or younger patients].

Objective: To explore the clinical features, biopsy results and risk factors of patients underwent prostate biopsy with age≤55, and to help make the proper treatment strategies of this cohort of patients. Methods: The data of patients with age≤55 underwent prostate biopsy between Jan 2011 and Nov 2013 was retrospectively reviewed. Clinical factors including prostate-specific antigen, digital rectal examination, ultrasonography and magnetic resonance imaging were recorded. Biopsy positive results were defined as the presence of prostate cancer and high-grade prostate cancer (Gleason score≥7). Results: There were all together 82 patients in this cohort, with the median age of 51 years old and median prostate-specific antigen of 8.62 µg/L. Among them 71 patients (86.6%) underwent pre-biopsy magnetic resonance imaging test, with 25 positive (35.2%), 18 suspicious (25.4%) and 28 negative results (39.4%). Pathology confirmed prostate cancer in 26 patients (31.7%), including 23 (28.0%) high-grade prostate cancer. Higher prostate-specific antigen, positive ultrasonography and positive magnetic resonance imaging were risk factors for prostate cancer and high-grade prostate cancer. For patients with prostate-specific antigen between 4 and 10 µg/L, 15.0% were diagnosed with prostate cancer, and positive ultrasound and magnetic resonance imaging were predictive for biopsy results. Conclusions: The positive rate of prostate biopsy in men younger than 55 years old is 31.7%, and the risk for prostate cancer of this cohort of patients shouldn't be neglected. Prostate-specific antigen value, ultrasonography and magnetic resonance imaging could help predict biopsy results.

Miniature and robust optical fiber in-line Mach-Zehnder interferometer based on a hollow ellipsoid.

An optical fiber in-line Mach-Zehnder interferometer based on a hollow ellipsoid fabricated by femtosecond laser micromachining and fusion-splicing technique is demonstrated. The surface of the hollow ellipsoid acts as an internal mirror that can be utilized for the construction of an interferometer. Such an interferometer device is miniature and robust and can perform external refractive index, curvature, and high-temperature sensing in a mutually independent way, and hence a simultaneous multiple parameter measurement capability can be readily achieved.

Downregulation of PLK1 by RNAi attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis and inhibiting angiogenesis.

Polo-like kinase 1(PLK1) is essential for the maintenance of genomic stability during mitosis. PLK1 has been reported to be upregulated in several solid tumors, including esophageal squamous cell carcinoma (ESCC). However, the role of PLK1 in tumorigenesis of ESCC remains undetermined. We used siRNA and lentivirus-mediated PLK1 RNA interference to investigate the tumor suppressor function of PLK1 reduction in ESCC cells. Flow cytometry and Terminal deoxynuleotidyl transferase-mediated nick-end labeling assay in vitro, as well as immunohistochemitry analysis of Caspase-3 and CD31 in s.c. tumor tissue section, were performed. Knock down of PLK1 expression significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar. PLK1 reduction mediated by lentivirus caused growth suppression of ESCC in nude mice. Caspase-3 upregulation further indicated that dysregulated apoptosis might contribute to reduced tumorigenecity. In particular, downregulation of CD31 suggested that PLK1 reduction-induced angiogenesis inhibition may also contribute, at least in part, to attenuated tumorigenecity. These findings indicate that PLK1 might play roles in tumorigenesis of ESCC and that PLK1 might be a potential gene therapy target in ESCC. Apoptosis induction together with decreased angiogenesis might be involved in the mechanism of tumor suppressor function of RNA interference targeting PLK1.

Association of BCSC-1 with human esophageal squamous cell carcinoma.

Breast cancer suppressor candidate-1 (BCSC-1) is a newly identified candidate tumor suppressor gene. BCSC-1 shows decreased levels in a variety of cancer types. In this study, we investigated the association between BCSC-1 and human esophageal squamous cell carcinoma (ESCC). BCSC-1 expression was detected in ESCC and normal tissues adjacent to tumor tissues by Western blot analysis and real-time PCR  as well as immunohistochemistry of paraffin sections. The relationships between BCSC-1 expression and various clinicopathological characteristics were analyzed. Western blot analysis and real-time PCR showed that levels of BCSC-1 protein and mRNA expression in ESCC significantly decreased compared with those in adjacent normal tissues.  Immunohistochemistry exhibited marked reduction of BCSC-1 in 38 of 105 ESCC specimens. Moreover, downregulation of BCSC-1 was associated with the grade of tumor cellular differentiation (P<0.05). These findings indicate that BCSC-1 downregulation in ESCC is associated with carcinogenesis and may play important roles during the process of ESCC cancer development.

Expression patterns of Doppel in differential ovine PRNP genotypes: quantification using real-time RT-PCR.

Doppel is a homologue of cellular prion protein (PrP)-like protein (PrPC). Different tissue samples were collected from the central nervous system plus four regions of lymphoid system, eleven regions of digestive tract and two reproductive organs from four ARR/ARQ and four ARH/ARQ sheep, genotypes of the PrP gene. Total RNA was isolated from these samples, and Doppel mRNA was quantified by real-time RT-PCR using SYBR Green. Doppel mRNA expression was higher in the ovary, hypothalamus and brain than in other tissues, and it significantly differed between the two genotypes in brain, ileum, cecum, rectum, colon, and uterus. This study demonstrated that Doppel mRNA expression in sheep with ARR/ARQ or ARH/ARQ genotypes was very different. These findings could be helpful in future studies of the relationship between PrP and Doppel.

[Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants].

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1st, 2019 to December 31st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

[Single-cell transcriptomic sequencing coupled with Mendelian randomization analysis elucidates the pivotal role of CTSC in chronic rhinosinusitis].

Objective: To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs. Methods: Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing. Results: An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes (CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC+cells in CRS. Conclusion: This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.