Utilizing metagenomic next-generation sequencing for pathogen detection and diagnosis in lower respiratory tract infections in real-world clinical practice.

BACKGROUND: Infectious etiologies of lower respiratory tract infections (LRTIs) by the conventional microbiology tests (CMTs) can be challenging. Metagenomic next-generation sequencing (mNGS) has great potential in clinical use for its comprehensiveness in identifying pathogens, particularly those difficult-to-culture organisms. METHODS: We analyzed a total of 205 clinical samples from 201 patients with suspected LRTIs using mNGS in parallel with CMTs. mNGS results were used to guide treatment adjustments for patients who had negative CMT results. The efficacy of treatment was subsequently evaluated in these patients. RESULTS: mNGS-detected microorganisms in 91.7% (188/205) of the clinical samples, whereas CMTs demonstrated a lower detection rate, identifying microorganisms in only 37.6% (77/205) of samples. Compared to CMT results, mNGS exhibited a detection sensitivity of 93.5% and 95.4% in all 205 clinical samples and 180 bronchoalveolar lavage fluid (BALF) samples, respectively. A total of 114 patients (114/201; 56.7%) showed negative CMT results, among which 92 received treatment adjustments guided by their positive mNGS results. Notably, 67.4% (62/92) of patients demonstrated effective treatment, while 25% (23/92) experienced a stabilized condition. Subgroup analysis of cancer patients revealed that 41.9% (13/31) exhibited an effective response to treatment, and 35.5% (11/31) maintained a stable condition following medication adjustments guided by mNGS. CONCLUSION: mNGS demonstrated great potential in identifying microorganisms of clinical significance in LRTIs. The rapid turnaround time and reduced susceptibility to the impact of antimicrobial administration make mNGS a valuable supplementary tool for diagnosis and treatment decision-making for suspected LRTIs in clinical practice.

Endometrial fluid aspiration immediately prior to embryo transfer does not affect IVF/vitrified-warmed embryo transfer outcomes - a prospective matched cohort study.

RESEARCH QUESTION: Does the endometrial aspiration of ultrasound-invisible fluid immediately preceding embryo transfer affect IVF/vitrified-warmed embryo transfer outcomes? DESIGN: A prospective matched cohort study was conducted in 96 women and 96 control participants to assess the effect on pregnancy outcomes of endometrial aspiration performed immediately before embryo transfer. This study was carried out at a university-affiliated assisted reproductive medical centre between January 2019 and December 2019. Patients were divided into two groups. The EA group had cycles with endometrial aspiration of ultrasound-invisible fluid performed before embryo transfer and the non-EA group featured cycles without endometrial aspiration. The EA group was matched by propensity score with the non-EA group in a 1:1 ratio. The EA group consisted of 99 participants before and 96 participants after propensity score matching. There were 203 and 96 participants in the non-EA group before and after propensity score matching. RESULTS: No significant differences were detected in the baseline characteristics and cycle characteristics of the EA and non-EA groups. No significant between-group differences were found in reproductive outcomes in the overall population. Subgroup analysis of blastocyst transfer cycles showed the implantation rate was significantly higher in the EA group (61 women per group, 57.1% versus 40.8%, relative risk 1.40, 95% confidence interval 1.04-1.88; P = 0.022). Live birth rate, clinical pregnancy rate, ongoing pregnancy rate and multiple pregnancy rate were not different among the groups. CONCLUSIONS: Endometrial aspiration immediately preceding embryo transfer does not affect IVF/vitrified-warmed embryo transfer outcomes. Interestingly, it might improve the vitrified-warmed blastocyst implantation rate. Randomized controlled trials are needed to confirm this result.

The associations of parental COVID-19 related worries, lifestyles, and insomnia with child insomnia during the COVID-19 outbreak.

The impacts of the Coronavirus Disease 2019 (COVID-19) pandemic on sleep health have been studied extensively. However, little is known about sleep problems within the family system during the pandemic. This study aimed to examine the influence of the COVID-19 pandemic on insomnia in both adults and children, and to explore whether parental COVID-19 related worries, lifestyles, and insomnia were associated with child insomnia. A total of 1355 parent-child dyads (39.2% fathers, mean age 38.37 years, SD = 5.34; 52.7% boys, mean age 12.47 years, SD = 1.67) were recruited from Jiangxi province in China from 4 to 18 February 2020. Data on insomnia, COVID-19 related worries, physical activity, and screen time were collected using online questionnaires. Path analysis showed that COVID-19 related worries and screen time were positively associated with insomnia in both parents and children; while children's physical activity was negatively related to children's insomnia. Parents' insomnia, COVID-19 related worries, physical activity, and screen time were positively associated with children's insomnia, COVID-19 related worries, physical activity, and screen time, respectively. Bootstrap tests showed that parents' worries were positively associated with children's insomnia via parents' insomnia and children's worries; parents' physical activity was negatively associated with children's insomnia via children's physical activity, parents' screen time was positively associated with children's insomnia via parents' insomnia and children's screen time. Both parental and child sleep are affected by the pandemic. Parental insomnia, stress reaction, and lifestyles contribute to child insomnia. Child sleep health may be maintained or improved by family bonds, home exercise, and sleep schedules.

Fertilization and neonatal outcomes after early rescue intracytoplasmic sperm injection: a retrospective analysis of 16,769 patients.

PURPOSE: To evaluate the efficacy and safety of short-term insemination and early-rescue intracytoplasmic sperm injection (ICSI), an approach that rescued oocytes with unclear second polar body 6 h after initial insemination by ICSI (early R-ICSI) to avoid total or near-total fertilization failure in conventional in vitro fertilization (IVF). METHODS: We performed a retrospective study in 16,769 patients (short-term IVF, n = 12,094; ICSI, n = 3452; early R-ICSI, n = 1223) who received IVF/ICSI treatment in our hospital from January 2009 to October 2018. Fertilization and clinical outcomes were compared among those three groups. RESULTS: When considering the R-ICSI embryos in the early R-ICSI group independently, the rates of fertilization and day-3 cleaved embryos in 2PN oocytes were comparable, the rates of fertilization (2PN) and high-quality embryos were lower, whereas the multi-PN fertilization rate (3.27%) was significantly higher than the ICSI group (1.26%). The difference of clinical pregnancy rate between the part of transferred R-ICSI embryos (40.81%) and the ICSI group (44.73%) remained nonsignificant. Furthermore, the rate of congenital birth defects in the early R-ICSI group (0.99%) was not significantly different from those in the short-term IVF (0.76%) and ICSI groups (1.07%). CONCLUSION: Despite the multi-PN fertilization rate, our study highlights early R-ICSI as a safe and effective alternative in assisted reproduction to decrease complete IVF fertilization failure and reduce ICSI utilization. Additional large amount and long-term follow-up studies are needed to further validate the use of early R-ICSI.

Overexpression of Tfap2a in Mouse Oocytes Impaired Spindle and Chromosome Organization.

Transcription factor AP-2-alpha (Tfap2a) is an important sequence-specific DNA-binding protein that can regulate the transcription of multiple genes by collaborating with inducible viral and cellular enhancer elements. In this experiment, the expression, localization, and functions of Tfap2a were investigated in mouse oocytes during maturation. Overexpression via microinjection of Myc-Tfap2a mRNA into the ooplasm, immunofluorescence, and immunoblotting were used to study the role of Tfap2a in mouse oocyte meiosis. According to our results, Tfap2a plays a vital role in mouse oocyte maturation. Levels of Tfap2a in GV oocytes of mice suffering from type 2 diabetes increased considerably. Tfap2a was distributed in both the ooplasm and nucleoplasm, and its level gradually increased as meiosis resumption progressed. The overexpression of Tfap2a loosened the chromatin, accelerated germinal vesicle breakdown (GVBD), and blocked the first polar body extrusion 14 h after maturation in vitro. The width of the metaphase plate at metaphase I stage increased, and the spindle and chromosome organization at metaphase II stage were disrupted in the oocytes by overexpressed Tfap2a. Furthermore, Tfap2a overexpression dramatically boosted the expression of p300 in mouse GV oocytes. Additionally, the levels of pan histone lysine acetylation (Pan Kac), histone H4 lysine 12 acetylation (H4K12ac), and H4 lysine 16 acetylation (H4K16ac), as well as pan histone lysine lactylation (Pan Kla), histone H3 lysine18 lactylation (H3K18la), and H4 lysine12 lactylation (H4K12la), were all increased in GV oocytes after Tfap2a overexpression. Collectively, Tfap2a overexpression upregulated p300, increased the levels of histone acetylation and lactylation, impeded spindle assembly and chromosome alignment, and ultimately hindered mouse oocyte meiosis.

Associations between dyslipidaemia and pregnancy outcomes in the first complete cycle of IVF/ICSI: a real-world analysis.

RESEARCH QUESTION: Are there associations between dyslipidaemia and pregnancy outcomes in the first complete cycle of IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: This long-term, retrospective real-world analysis involved 5030 infertile women who underwent a first complete IVF/ICSI cycle between January 2015 and October 2020. They were categorized into dyslipidaemia (n = 1903) and control (n = 3127) groups according to serum lipid concentrations before ovarian stimulation. Propensity score matching and multivariable logistic regression were used to control for confounding variables. RESULTS: In the raw cohort, women with dyslipidaemia had a significantly increased late miscarriage rate (P = 0.039), decreased term birth rate (P = 0.002) and decreased live birth rate (P = 0.005) compared with non-dyslipidaemic women. In the propensity score-matched cohort, the term birth rate (P = 0.038) and live birth rate (P = 0.044) were significantly lower in the dyslipidaemia group (n = 1686) than the controls (n = 1686). Multivariable logistic regression indicated that infertile women with dyslipidaemia (P = 0.026) and elevated serum total cholesterol concentrations (total cholesterol ≥5.20 mmol/l; P = 0.028) were significantly less likely to have a live birth. Rates of late miscarriage (P = 0.027), term birth (P = 0.003) and live birth (P = 0.010) differed significantly among women with normal, borderline increased and increased serum lipid concentrations. Compared with controls, women with increased serum lipid concentrations had a significantly higher late miscarriage rate, lower term birth rate and lower live birth rate. Women with increased serum lipid concentrations were significantly less likely than controls to have a live birth. CONCLUSIONS: Dyslipidaemia, total cholesterol ≥5.20 mmol/l and degrees of elevated serum lipid concentrations are negatively associated with live birth rate in the first complete IVF/ICSI cycle in infertile women.

The Prevalence of Euthyroid Hypertriiodothyroninemia in Newly Diagnosed Multiple Myeloma and its Clinical Characteristics.

OBJECTIVE: To evaluate the prevalence of euthyroid hypertriiodothyroninemia and/or hyperthyroxinemia and its clinical characteristics in multiple myeloma (MM) patients. METHODS: Previously untreated, newly diagnosed patients with MM were enrolled at the Beijing Chao-yang Hospital between January 2016 and December 2019. Thyroid function and clinical characteristics were analyzed. RESULTS: A total of 105 patients were enrolled in this study. Thirteen (12.38%) patients exhibited euthyroid hypertriiodothyroninemia with strikingly elevated total triiodothyronine (TT3) levels (>8 ng/mL). Among these 13 patients, 12 patients were immunoglobulin (Ig) G type (92.31%), and 1 patient was light-chain κ type (7.69%). Compared with other patients with MM, patients with hypertriiodothyroninemia were more likely to be IgG type and had higher serum globulin and lower albumin levels and more advanced International Staging System stage (all P < .05). Among the 13 euthyroid hypertriiodothyroninemia patients, 8 patients have been followed up and checked for thyroid function. The TT3 levels in all 8 patients were normalized to the reference range after antimyeloma chemotherapy. CONCLUSION: About 12% of patients with MM had euthyroid hypertriiodothyroninemia. Their strikingly elevated TT3 was normalized after chemotherapy. Clinicians should be aware of the possibility of high TT3 levels in euthyroid patients with MM and the potential risk of MM in patients with strikingly elevated TT3.

Investigation on Atypical Pathogens related with Community Acquired Pneumonia and the Factors Associated with Mycoplasma Pneumoniae Infection in Jiangsu, China.

BACKGROUND: Community acquired pneumonia remains a leading infectious cause of hospitalization with substantial morbidity and mortality in China. At present, the role of atypical pathogens in CAP arouses peoples' concern. Previous studies indicated that MP was the dominant pathogen of CAP, but the associated factors of MP infection were rarely reported. METHODS: We retrospectively investigated the distribution of atypical pathogens related with CAP and compared their differences among various populations. Furthermore, we accessed the associated factors of MP infection in various population. RESULTS: A total of 3,675 patients were enrolled and divided into three groups. One thousand and eighty-nine subjects (29.6%) were infected with at least one atypical pathogen. MP was the most predominant pathogen in these CAP patients. Our study found that infection rates of the atypical pathogens were significantly different among three groups. Our results also revealed, in a pediatric group, as the temperature increased, so did the infection rate of MP, while it was the opposite in adult and elderly groups. Furthermore, in preschool and school-age children, high temperature, female, PIVs, ADV, and INFB infection were independent risk factors for MP infection, INFA infection was a protection factor for MP infection. However, in adult and elderly groups, the associated factors might be different. CONCLUSIONS: The infection of atypical pathogens related with CAP is quite serious, and MP infection plays a key role in CAP. Besides, the infection rates of the atypical pathogens are different in various populations, as are the associated factors for MP infection.

Systematic Understanding of Mechanism of Yi-Qi-Huo-Xue Decoction Against Intracerebral Hemorrhagic Stroke Using a Network Pharmacology Approach.

BACKGROUND Intracerebral hemorrhage (ICH), a fatal type of stroke, profoundly affects public health. Yi-Qi-Huo-Xue decoction (YQHXD), a traditional Chinese medicine (TCM) prescription, is verified to be an efficient method to treat ICH stroke among the Chinese population. Nevertheless, the pharmacological mechanisms of YQHXD have been unclear. MATERIAL AND METHODS We used a strategy based on network pharmacology to explore the possible multi-component, multi-target, and multi-pathway pattern of YQHXD in treating ICH. First, candidate targets for YQHXD were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then, these candidate YQHXD targets were used in combination with the known targets for the treatment of ICH stroke to construct the core network (cPPI) using data on protein-protein interaction (PPI). We calculated 5 topological parameters for identification of the main hubs. Pathway enrichment and GO biological process enrichment analyses were performed after the incorporation of the main hubs into ClueGO. RESULTS In total, 55 candidate YQHXD targets for ICH were recognized to be the major hubs in accordance with their topological importance. As suggested by enrichment analysis, the YQHXD targets for ICH were roughly classified into several biological processes (related to redox equilibrium, cell-cell communication, adhesion and collagen biosynthesis, cytokine generation, lymphocyte differentiation and activation, neurocyte apoptosis and development, neuroendocrine system, and vascular development) and related pathways (VEGF, mTOR, NF-kappaB, RAS/MAPK, JAK/STAT and cytokine-cytokine receptors interaction), indicating those mechanisms underlying the therapeutic effect of YQHXD. CONCLUSIONS The present results may serve as a pharmacological framework for TCM studies in the future, helping to promote the use of YQHXD in clinical treatment of ICH.

Identification of factors related to fertilization failure in in vitro fertilization-embryo transfer. / 体外受精-èƒšèƒŽç§»æ¤ä¸­å—ç²¾å¤±è´¥çš„ç›¸å ³å› ç´ .

OBJECTIVES: To investigate the possible factors relevant to fertilization failure in in vitro fertilization-embryo transfer (IVF-ET). METHODS: The medical records of 4 205 infertile patients undergoing IVF-ET treatment at the Reproductive Medicine Center, Xiangya Hospital, Central South University from January 2016 to December 2017 were collected. The patients were divided into a complete fertilization failure group, a low fertilization rate group, and a control group based on fertilization rate. We examined the associations among the 3 groups in terms of female age, duration of infertility, duration of stimulation, gonadotropin (Gn) dosage, follicle-stimulating hormone (FSH) dosage, and total number of retrieved oocytes. According to theincidence factors, the patients were divided into a single female factor group, a single male factor group and a unisex factor group, and the correlation analysis of incidence factor among the 3 groups was performed. The patients were divided into a primary infertility and a secondary infertility in accordance with the type of infertility. We analyzed the correlation of infertility type among the three groups. Risk factors for complete fertilization failure and low fertilization rate in IVF-ET were obtained by stepwise multiple linear regression analysis. RESULTS: Primary infertility, long infertility duration, total number of retrieved oocytes, and unisex factor were associated with completefertilization failure and low fertilization rate in IVF-ET (P<0.05), but female age, duration of stimulation, FSH dosage as well as Gn dosage were not correlated with complete fertilization failure and low fertilization rate in IVF-ET (P>0.05). Stepwise multiple linear regression analysis showed that the incidence factor, type of infertility, and infertility duration were independent influential factors for complete fertilization failure and low fertilization rate. CONCLUSIONS: Complete fertilization failure and low fertilization rate in IVF-ET are related to duration of infertility, total number of retrieved oocytes, cause of onset, and type of infertility, but they are not relevant to female age, duration of stimulation, and Gn and FSH dosage.

TGF-ß Signaling Induces the Expression of OPN in Blood Vessel Endothelial Cells.

BACKGROUND: The mechanism of blood vessel formation and degeneration still remains unclear. Transforming growth factor-ß1 (TGF-ß1) signaling is a critical pathway in this progression and can induce multiple biological effects. Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response associated with vascular calcification. METHODS: To identify the relationship between TGF-ß signaling pathway and OPN, we stimulated human vascular endothelial cells (HVECs) and human aortic endothelial cells (HAECs) using various concentration of TGF-ß1 in vitro. RESULTS: As assessed by flow cytometry and western blots, apoptosis levels were significantly increased with TGF-ß1 treatment. We also demonstrated that OPN increased in vitro with TGF-ß signaling by western blot and quantitative real time polymerase chain reaction (qRT-PCR) analyses. The inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) was also up-regulated by TGF-ß signaling. Meanwhile, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were down-regulated. CONCLUSIONS: Taken together, our findings demonstrate that TGF-ß signaling can induce the expression of OPN, which may play an important role in the dysfunction of the vascular wall.

Long-Term Outcome of Catheter-Directed Thrombolysis in Pregnancy-Related Venous Thrombosis.

BACKGROUND Venous thromboembolism (VT) is a leading cause of maternal mortality and morbidity worldwide. Catheter-directed thrombolysis (CDT) is an effective and safe treatment modality for VT patients. However, the long-term outcome of CDT in pregnancy-related venous thrombosis are unclear. The aim of this study was to assess long-term results of pregnancy-related VT patients. MATERIAL AND METHODS We reviewed 41 pregnancy-related deep venous thrombosis (DVT) patients who underwent CDT from February 2008 to May 2015. Clinical data, including demographic variables, disease location, vascular risk factors, treatment regimen, interventional procedure and complications, were collected retrospectively. Clinical and color-duplex ultrasonography were performed to monitor venous patency during follow-up. Post-thrombotic syndrome (PTS) was assessed with the Villalta scale and quality of life (QOL) was evaluated by the VEINES-QOL/Sym questionnaire. RESULTS Twenty-three patients underwent spontaneous abortion or induced abortion within 3 months before DVT, and 18 patients had DVT during the first 3 months after delivery. Technical success was achieved in all patients. Grade III (complete) lysis was obtained in 15 patients and grade II (partial) lysis was obtained in 21 patients. The follow-up period was 3 years. Twenty-eight patients had venous patency at 3-year follow-up; 36.6% of patients developed mild or moderate PTS (Villalta score 5-14) and 4.8% with severe PTS (Villalta score ≥15). VEINES-QOL/Sym scores were 55.24±7.35 and 53.25±6.65, respectively. CONCLUSIONS Catheter-directed thrombolysis is a reliable and safe treatment modality for postnatal or abortion patients with DVT. CDT can reduce the incidence rate of PTS and increase the quality of life.

A dereplication strategy for identifying triterpene acid analogues in Poria cocos by comparing predicted and acquired UPLC-ESI-QTOF-MS/MS data.

INTRODUCTION: Triterpene acids from the dried sclerotia of Poria cocos (Schw.) Wolf (poria) were recently found to possess anti-cancer activities. Identification of more triterpene acid analogues in poria is worthwhile for high throughput screening in anti-cancer drug discovery. OBJECTIVE: To establish an efficient dereplication strategy for identifying triterpene acid analogues in poria based on ultra-performance liquid chromatography with electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS). METHODOLOGY: The structural characteristics and mass spectrometric data profiles of known triterpene acids previously reported in poria were used to establish a predicted-analogue database. Then, the quasi-molecular ions of components in a poria extract were automatically compared with those in the predicted-analogue database to highlight compounds of potential interest. Tentative structural identification of the compounds of potential interest and discrimination of isomers were achieved by assessing ion fragmentation patterns and chromatographic behaviour prediction based on structure-retention relationship. RESULTS: A total of 62 triterpene acids were unequivocally or tentatively characterised from poria, among which 17 triterpene acids were tentatively identified for the first time in poria. CONCLUSION: This study provided more structure information of triterpene acids in poria for future high throughput screening of anti-cancer candidates. It is suggested that this semi-automated approach in which MS data are automatically compared to a predictive database may also be applicable for efficient screening of other herbal medicines for structural analogues of proven bioactives.

Resveratrol Improves Endothelial Progenitor Cell Function through miR-138 by Targeting Focal Adhesion Kinase (FAK) and Promotes Thrombus Resolution In Vivo.

BACKGROUND Endothelial progenitor cells (EPCs) were found to be a potential therapeutic choice for low extremity deep vein thrombosis. The aim of our research was to investigate the effect of resveratrol (RSV) on EPCs that may promote thrombus resolution and its potential pathway. MATERIAL AND METHODS EPCs were pretreated with RSV and migration; angiogenesis were evaluated ex vivo. Expression of miR-138 and focal adhesion kinase (FAK) was also tested. A murine model of venous thrombosis was developed as an in vivo model. The effects of RSV treatment on mice with inferior venous thrombosis were evaluated. RESULTS We found that RSV increased EPCs migration and tube formation ex vivo. RSV significantly inhibited miR-138 expression. Moreover, we demonstrated that FAK was a target of miR-138 and revealed that FAK knockdown downregulated migration and angiogenesis of RSV-treated EPCs. In addition, RSV-induced EPCs promoted thrombus resolution in a murine model of venous thrombosis. CONCLUSIONS We found the first evidence that intravenous injection of RSV-treated EPCs enhanced thrombus resolution in vivo. RSV exerted its role by reducing miR-138 expression and therefore upregulated FAK.

Low Computational Signal Acquisition for GNSS Receivers Using a Resampling Strategy and Variable Circular Correlation Time.

For the objective of essentially decreasing computational complexity and time consumption of signal acquisition, this paper explores a resampling strategy and variable circular correlation time strategy specific to broadband multi-frequency GNSS receivers. In broadband GNSS receivers, the resampling strategy is established to work on conventional acquisition algorithms by resampling the main lobe of received broadband signals with a much lower frequency. Variable circular correlation time is designed to adapt to different signal strength conditions and thereby increase the operation flexibility of GNSS signal acquisition. The acquisition threshold is defined as the ratio of the highest and second highest correlation results in the search space of carrier frequency and code phase. Moreover, computational complexity of signal acquisition is formulated by amounts of multiplication and summation operations in the acquisition process. Comparative experiments and performance analysis are conducted on four sets of real GPS L2C signals with different sampling frequencies. The results indicate that the resampling strategy can effectively decrease computation and time cost by nearly 90-94% with just slight loss of acquisition sensitivity. With circular correlation time varying from 10 ms to 20 ms, the time cost of signal acquisition has increased by about 2.7-5.6% per millisecond, with most satellites acquired successfully.

[Thought and method of classic formulae in treatment of chronic cough].

Chronic cough is a common clinical disease with complex etiology, which is easily misdiagnosed and mistreated. Chronic cough guideline has been developed based on the modern anatomical etiology classification, and it may improve the level of diagnosis and treatment. Common causes of chronic cough are as follows: cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, gastroesophageal reflux-related cough, post-infectious cough, etc. There is a long history and rich experience in treatment of cough in traditional Chinese medicine which is characterized by syndrome differentiation. The four elements of pathogenesis for chronic cough include wind, phlegm, fire, and deficiency. Classic formula is widely used in the treatment of chronic cough, and the focus is on prescriptions corresponding to syndromes. This article attempts to explore the thought and method of classic formulae in treatment of chronic cough based on three perspectives: differentiation of etiology, pathogenesis and formula-syndrome. Three medical cases are selected at last in order to prove its correction.

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

OBJECTIVES: To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. METHODS: A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. RESULTS: Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. CONCLUSION: Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. KEY POINTS: • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.

Bidirectional Pull-Back Technique for Retrieval of Strut-Embedded Cylinder-Shaped Filters in Inferior Vena Cava.

BACKGROUND IVC filters have been widely accepted as an effective method to prevent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT). However, the placement of IVC filters is associated with significant complications and filter retrieval can be challenging when the filter struts are embedded into the caval wall. MATERIAL AND METHODS Over 26 months, we reviewed the safety and efficacy of the bidirectional pull-back technique for removing strut-embedded IVC filters in 15 consecutive patients. Retrieval procedural data such as in-dwell time, retrieval time, and fluoroscopy time were recorded. Clinical outcomes and procedure-related complications were evaluated by venography or enhanced computed tomography. Histologic tissue was analyzed to reveal the pathologic effects of chronic filter implantation. All patients underwent routine clinical follow-up at a mean time of 12 months (range, 8-14 months). RESULTS Technical success of filter retrieval was achieved in 100%, with mean implantation of 46.6 days (range, 27-66 days). Filter types were as follows: OptEase (n=11) and Aegisy (n=4). The mean retrieval time and fluoroscopy time were 21.43±5.42 min and 7.63±2.67 min, respectively. Immediate postprocedure venography showed no procedure-related complications. Thirteen patients discontinued previously prescribed lifelong anticoagulation. There were no long-term complications during follow-up. CONCLUSIONS The bidirectional pull-back technique is safe and efficient for filter retrieval. This complex technique can be particularly useful in selected patients to remove strut-embedded cylindrical-shaped IVC filters previously considered irretrievable.

Systematic review and meta-analysis of Tuberculosis and COVID-19 Co-infection: Prevalence, fatality, and treatment considerations.

BACKGROUND: Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. METHODS: This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. RESULTS: From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18-3.68) for TB-COVID patients versus single COVID patients. CONCLUSION: TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection.

Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising therapeutic target in prostate cancer (PCa). Understanding the mechanisms of BRD4 stability could enhance the clinical response to BRD4-targeted therapy. In this study, we report that BRD4 protein levels are significantly decreased during mitosis in a PLK1-dependent manner. Mechanistically, we show that BRD4 is primarily phosphorylated at T1186 by the CDK1/cyclin B complex, recruiting PLK1 to phosphorylate BRD4 at S24/S1100, which are recognized by the APC/CCdh1 complex for proteasome pathway degradation. We find that PLK1 overexpression lowers SPOP mutation-stabilized BRD4, consequently rendering PCa cells re-sensitized to BRD4 inhibitors. Intriguingly, we report that sequential treatment of docetaxel and JQ1 resulted in significant inhibition of PCa. Collectively, the results support that PLK1-phosphorylated BRD4 triggers its degradation at M phase. Sequential treatment of docetaxel and JQ1 overcomes BRD4 accumulation-associated bromodomain and extra-terminal inhibitor (BETi) resistance, which may shed light on the development of strategies to treat PCa.