Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

Objective To study the diagnostic value of serum long chain non coding RNA(lncRNA)CB-SLR,α trypsin H4 heavy chain(ITIH4)in early gastric cancer in the elderly.Methods From 2020 to 2022,a total of 90 elderly patients with early gastric cancer diagnosed and treated in the hospital were selected as the early gastric cancer group,while 45 patients with chronic atrophic gastritis diagnosed and treated in the same period were selected as atrophic gastritis group and 45 healthy people undergoing physical examination in the same period were selected as the healthy control group.The serum levels of lncRNA CBSLR and ITIH4 in each group were detected by fluorescence quantitative PCR and enzyme linked immunosorbent assay.Pearson correlation analysis was performed to determine the correlation between serum lncRNA CBSLR and ITIH4 levels with tumor markers carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)19-9.The levels of serum lncRNA CBSLR and ITIH4 among patients with different clinicopathological characteristics were com-pared.The diagnostic value of serum lncRNA CBSLR and ITIH4 in elderly patients with early gastric cancer was analyzed by receiver operating characteristic curve.Results The serum levels of lncRNA CBSLR,ITIH4,CEA and CA19-9 in the early gastric cancer group were significantly higher than those in the atrophic gastritis group and health control group(all P＜0.05).There was significant positive correlation between serum ln-cRNA CBSLR,ITIH4 and CEA,CA19-9 levels in patients with early gastric cancer(r=0.601-0.751,all P＜0.05).In patients with early gastric cancer,serum IncRNA CBSLR and ITIH4 were related to tumor diame-ter,depth of invasion,differentiation type,and lymph node metastasis(all P＜0.05),but not related to age,gender,tumor location,and gross type(all P＞0.05).The area under the curve of combined detection of ser-um lncRNA CBSLR,ITIH4,CEA and CA19-9(0.912,95％CI:0.858-0.949)for the diagnosis of early gas-tric cancer was higher than that of serum lncRNA CBSLR(0.833,95％CI:0.784-0.879),ITIH4(0.806,95％CI:0.760-0.847),CEA(0.791,95％CI:0.742-0.830),and CA19-9(0.766,95％CI:0.710-0.815)alone(Z=4.482,5.130,5.231,6.117,all P＜0.05).Conclusion The elevated levels of serum lncRNA CB-SLR and ITIH4 in elderly patients with early gastric cancer are associated with adverse clinicopathological characteristics of gastric cancer.The combination of serum lncRNA CBSLR,ITIH4,CEA and CA19-9 has high diagnostic value for elderly patients with early gastric cancer.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Ménière's disease （MD） is an inner ear disease characterized by vertigo， tinnitus， hearing loss， and ear stuffiness. Modern therapies such as drugs， surgery， and vestibular function rehabilitation have limited effects in relieving the symptoms and reducing the recurrence. Traditional Chinese medicine （TCM） can alleviate the symptoms of MD with simple operation and mild adverse reactions while emphasizing psychological adjustment. The TCM treatment of MD is individualized depending on different stages and pathogenic factors. The internal treatment mainly targets phlegm， dampness， water， wind， fire， deficiency， and blood stasis. External interventions include acupuncture and moxibustion. This paper reviewed the published articles about the treatment of MD with TCM. In recent five years， the published studies were mainly clinical trials and experience discussion （or case reports）， and few reports of fundamental research were published. In these studies， the Western medicine diagnosis of MD mostly refers to the Diagnostic Basis and Efficacy Evaluation of Ménière's Disease （Guiyang， 2006） and the Guidelines for Diagnosis and Treatment of Ménière's Disease （2017）， while the TCM diagnosis mostly refers to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine issued by the National Administration of TCM in 1994. The efficacy was mostly evaluated based on clinical efficacy， scales， syndrome scores， pure tone audiometry， etc.， while caboratory indexes were rarely used. The available clinical studies about the treatment of MD with TCM generally have low quality of evidence and single intervention means. In the future， the research on the treatment of MD with TCM can be improved by standardizing the research program， improving the quality of evidence， exploring more intervention methods， and strengthening basic research.

Abstract: Objective To clarify the long-term evolution of hepatitis B virus (HBV) quasi-species in HBsAg asymptomatic carriers in Long'an county, Guangxi. Methods ELISA was used to detect serological markers of HBV. Viral loads were measured by real time PCR. HBV DNA was extracted from serum by kits. The whole HBV genome was amplified using nested PCR and amplicons were sequenced by next-generation sequencing (NGS). These sequences from NGS were analyzed by the software like Mega. Results Serum samples were collected from 9 HBsAg asymptomatic carriers in Longan County，Guangxi at 4 different time points in 2004, 2007, 2013, 2019 or 2020. A total of 23 serum samples and 309 full-length gene quasi-species sequences were obtained, with an average amount of (0.18±0.07) G sequencing data for each sample. Genotype of 55.54%(5/9) the studied subjects underwent genotype conversion during the long-term evolution process of HBV quasi-species, and the genotyping results of the phylogenetic tree in the PreS/S region are in perfect agreement with the results of the whole genome analysis; recombinant B/C, I/C were found; the Sn ranged from 0 to 0.37 and the genetic diversity ranged from 0 to 0.11, respectively. A total of 21 special single nucleotide/amino acid mutations (7 in the S region, 2 in the X region, 3 in the PreC region and 9 in the BCP region) and 6 deletion mutations were detected, multiple mutations were found and no drug resistant mutations were found; 77.8%(7/9) of the HBV strains carried by the subjects in 2004 had double mutations at nt1 762(A→T) and 1 764(G→A) and a stop mutation at nt1 896(G→A); HBV mutations can be restored from the mutant type to the wild type and (or) vice versa without antiviral drug pressure, and The evolution rate of HBV genome was 2.03×10-5~3.50×10-3.Conclusion HBV genotype, recombinants, genetic complexity and diversity of HBV quasi-species can change over time during in natural infection. The transformation between HBV mutation type and wild type reduces the value of predicting clinical outcomes by genetic types and related mutations to some extent. The HBV genome evolution rate of asymptomatic carriers of HBsAg in Long'an County is very high.

OBJECTIVE To report the analysis and treatment of liver function injury caused by heparin sodium injection in the positive control group in an early clinical study of new drugs, in order to provide reference for the clinical use of heparin sodium injection and provide ideas for the treatment of adverse reactions. METHODS Analyzed and summarized one case of liver injury in a tolerance and pharmacokinetics study of a new anticoagulant drug with both placebo and heparin sodium as control, described the case process, analyzed the cause, and discussed the enlightenment for treatment of adverse event in early clinical research and the safety of heparin sodium in clinical use. RESULTS Three cases occurred different degrees increasing of alanine aminotransferase and aspartate aminotransferase after 4 healthy subjects were infused with heparin sodium for 5 consecutive days. It was considered that those were adverse reactions caused by heparin sodium. Timely treatment was performed by strengthening monitoring and administrating liver protective drugs. Protocol was revised to avoid further injury to the follow-up subjects. CONCLUSION Continuous infusion of heparin sodium injection can easily cause liver function damage, and should be given sufficient attention during clinical use. Early clinical research should promptly analyze and handle adverse reactions to ensure the safety of subjects.

Objective:To investigate the immune effects of Clostridium difficile toxoid B (CdtB) vaccine formulated with different mucosal adjuvants through microneedle immunization, and to provide ideas for the prevention and treatment of Clostridium difficile infection. Methods:CdtB vaccine was prepared with purified Clostridium difficile toxin B(TcdB) after formaldehyde detoxification. Female BALB/c mice were immunized with different doses of vaccine alone or in combination with mucosal adjuvants. The titers of specific serum IgG and fecal IgA were detected at 0 d, 7 d, 14 d, 28 d and 42 d after immunization. The protective effects of CdtB vaccine were evaluated by cell neutralization assay and Clostridium difficile challenge infection. Results:(1) With the increase of immune dose, the mice immunized with CdtB vaccine alone by microneedle not only produced better serum specific IgG, but also had higher level of IgA in feces. (2) When the mice were immunized with CdtB vaccine containing LT or CTB adjuvant by microneedle, the trend of serum specific IgG titer in each group increased with the increase of immune dose, especially in the group containing LT adjuvant. There were significant differences in the trend of specific IgA titer in feces between the adjuvant groups and the group without adjuvant, but the adjuvant effect was not obvious. (3) No significant difference in serum IgG titer was observed between the mice immunized with 10 μg CdtB by microneedle or intraperitoneal injection, but microneedle immunization significantly increased fecal IgA level. (4) The neutralization titers of specific antibodies in mouse serum after immunization and the test results of challenge protection in mice confirmed that the use of CdtB vaccine had certain protective effects.Conclusions:CdtB vaccine had better immune effects in mice through microneedle immunization, but the adjuvant effects of LT and CTB were not significant.

Objective:To explore the effect of emergency nursing based on de-escalation thinking in patients with acute pancreatitis.Methods:From January 2019 to December 2020, 156 patients with acute pancreatitis in the Emergency Department of Beijing Friendship Hospital, Capital Medical University were retrospectively selected as the research object by convenience sampling. According to different nursing methods, the patients were divided into the control group and the intervention group with 78 cases in each group. The control group received routine nursing, and the intervention group implemented emergency nursing based on de-escalation thinking on the basis of the control group. The incidence of complications, treatment effect and nursing satisfaction were compared between the two groups.Results:The incidence of complications in the intervention group was lower than that in the control group, the total treatment effective rate was higher than that in the control group, and the patients in the intervention group were more satisfied with nursing skills, health education, and emergency measures than the control group, with statistical differences ( P<0.05) . Conclusions:Emergency nursing based on de-escalation thinking in patients with acute pancreatitis can effectively reduce the incidence of complications, improve the first aid effectiveness, and nursing satisfaction, which is worthy of clinical application.

Objective:To explore the demand and mode of palliative care for emergency dying patients by analyzing the case data of emergency death and cardiopulmonary resuscitation.Methods:The data of 776 cases of emergency clinical death and cardiopulmonary resuscitation in the Second Affiliated Hospital of Soochow University from 2017 to 2020 were retrospectively analyzed.Results:A total of 687 patients were included with (70.38 ± 16.57) years old, and 49.8% (342/687) of them were 75 years old and above; among them, 36.0% (247/687) patients or their families chose not to give cardiopulmonary resuscitation (DNR) in the last stage of their lives,and 63.2%(156/247) of DNR patients were 75 years old and above. The top four etiology of DNR were cerebral hemorrhage, respiratory failure, multiple organ dysfunction syndrome and out of hospital cardiac and respiratory arrest.After successful cardiopulmonary resuscitation, 37.5% (45/120) of the patients' family members chose to give up treatment again. The median stay time of DNR patients in the emergency room was 738.7 minutes.Conclusions:The patients who choosed DNR were mainly 75 years old and above, with cerebral hemorrhage, respiratory failure, multiple organ failure and cardiac and respiratory arrest. The detention of these patients in the emergency room increases the congestion of the emergency room, and at the same time, they can not get a peaceful palliative care environment. It is suggested that emergency medical staff should strengthen the awareness and improve the ability of palliative care. A relative independent area and corresponding soothing palliative treatment and nursing should be given to the DNR patients.