This paper summarized the clinical experience of Professor HE Chengyao in treating recurrent miscarriage complicated with subclinical hypothyroidism. It is believed that kidney yang insufficiency is the root of the disease， while the functional decline of the five zang （脏） organs and the obstruction of the sanjiao （三焦） pivot are the key links of the pathogenesis. In clinical practice， the division of yang numbers in the Book of Changes （《周易》） is followed， and 9 months is advocated as the basic treatment cycle for recurrent miscarriage complicated with subclinical hypothyroidism. During the first half of the period before pregnancy （the first 3 months）， it is recommended to warm the pivot and sanjiao （三焦）， and Yougui Pills （右归丸） is commonly used as the basic prescription to warm and supplement the kidney yang， together with the medicinals of invigorating blood and dissolving stasis， regulating and unblocking qi movement. During the second half of the period before pregnancy （the second 3 months）， it is better to nourish essence and nature the embryo commonly with Wuzi Yanzong Pills （五子衍宗丸） in modification. After pregnancy （the third 3 months）， it is suggested to supplement kidney and consolidate chong mai （冲）， replenish qi and nourish blood mainly， supplemented by warming and nourishing heart yang， and self-made Bushen Antai Formula （补肾安胎方） which is modified based on the combination of Shoutai Pills （寿胎丸） and Wenbao Beverage （温胞饮） is commonly used.Additionally， it is recommended to adjust lifestyle and diet so as to balance yin and yang and improve the physical condition.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Pheochromocytomas and paragangliomas are rare but therapeutically challenging neuroendocrine tumors in urology. Surgical treatment has been recognized as a definitive treatment. However, traditional surgical methods present certain risks and limitations. The Da Vinci robotic surgery offers a new approach for treating these tumors. This review elucidates the technical features, clinical applications, and treatment outcomes of Da Vinci robotic surgery and the progress in the treatment of pheochromocytomas and paragangliomas. In addition, this review discusses the prospects of combining Da Vinci robotic surgery with other emerging technologies, emphasizing the further research to validate its long-term efficacy and safety.

Pheochromocytomas and paragangliomas are rare but therapeutically challenging neuroendocrine tumors in urology. Surgical treatment has been recognized as a definitive treatment. However, traditional surgical methods present certain risks and limitations. The Da Vinci robotic surgery offers a new approach for treating these tumors. This review elucidates the technical features, clinical applications, and treatment outcomes of Da Vinci robotic surgery and the progress in the treatment of pheochromocytomas and paragangliomas. In addition, this review discusses the prospects of combining Da Vinci robotic surgery with other emerging technologies, emphasizing the further research to validate its long-term efficacy and safety.

Objective:To investigate the effect of quality improvement (QI) project on delayed cord clamping (DCC) implementation in very preterm infants.Methods:This study retrospectively collected the clinical data and assessed the QI indices of very preterm infants born in the Women and Children's Hospital of Chongqing Medical University and transferred to the Neonatology Department from January 2017 to January 2021. The indices for QI assessment included three types: (1) process indices: the implementation rate and timing of DCC; (2) outcome indices: hemoglobin level and hematocrit, etc; (3) balancing indices: the proportion of neonates requiring endotracheal intubation in the delivery room and chest compressions, Apgar score body temperature, and blood pH value on admission, etc. There were four phases for the implementation of QI, the pre-QI period (January to December of 2017), the QI period (January to December of 2018), the post-QI period (January to December of 2019), and the sustained-QI period (January 2020 to January 2021). The QI project was performed since August 2018. Control charts or statistical tests were used for statistical analysis.Results:(1) Process indices: After the implementation of the QI project, the practice of DCC increased from 0 to 82.2%, and the timing of umbilical cord clamping was from 0 s to a delay of 47.1 s. (2) Outcome indices: The levels of hemoglobin in the QI period, the post-QI period, and the sustained-QI period were significantly higher than those in the pre-QI period [(202.22±28.84), (210.10±33.52), (210.52±32.27) g/L vs. (187.94±35.29) g/L; F=8.61, P<0.001]. The hematocrit values in the post-QI period and the sustained-QI period were significantly higher than those in the pre-QI period [(58.99±8.71) %, (60.18±8.06)% vs. (55.41±9.17)%; χ2=5.13, P=0.002]. The other indices showed no statistical differences in different phases. (3) Balancing indices: The proportions of neonates receiving endotracheal intubation in the delivery room in the post-QI period and the sustained-QI period were significantly lower than those in the pre-QI period [16.0% (19/119), 13.2% (25/191) vs. 42.3% (30/71); χ2=29.08, P<0.001]. The body temperature on admission increased gradually through the four periods [pre-QI period: 35.3 ℃ (34.5-36.1 ℃); QI period: 36.0 ℃ (34.0-37.7 ℃); post-QI period: 36.0 ℃ (35.6-37.4 ℃); sustained-QI period: 37.0 ℃ (35.9-38.1 ℃); H=277.88, P<0.001]. The blood pH value on admission in the sustained-QI period [7.32 (6.85-7.50)] was significantly higher than those in the other three periods [7.26 (7.07-7.46), 7.26 (7.04-7.43), and 7.25 (6.91-7.49); H=34.46, P<0.001]. Conclusion:The interventions in this QI project significantly increase the practice of DCC and enable a longer DCC in very preterm infants.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Objective:To explore the clinical therapeutic effect and follow-up prognosis of preterm infants with neonatal respiratory distress syndrome (NRDS) managed by less invasive surfactant administration (LISA) and traditional intubation-surfactant-extubation (INSURE) of pulmonary surfactant (PS).Methods:Data during hospitalization and follow-up period of 187 NRDS preterm infants (gestational age 24 weeks to 31 + 6 weeks, and birth weight <1 500 g) admitted to the Department of Neonatology, the Women and Children′s Hospital of Chongqing Medical University from March 2019 to February 2021 were retrospectively analyzed.NRDS preterm infants who were injected with PS by LISA were included in the LISA group (144 cases), and those who were injected with PS by INSURE were included in the INSURE group (43 cases). The propensity score matching method was used to correct the confounding factors between groups, and the covariate equilibrium samples between groups were obtained (39 cases in each group). Clinical treatment effect and prognosis of physical development, hearing and vision development, nervous system development, respiratory system diseases and other conditions of the two groups of children were compared using the t test, Chi- square test and other statistical analysis methods as appropriate. Results:(1)Compared with that of the INSURE group, the incidence of BPD [12 cases (33.3%) vs.23 cases (63.9%), χ2=6.727, P=0.009] and ROP [13 cases (36.1%) vs.26 cases (72.2%), χ2=9.455, P=0.002] in the LISA group were significantly lower.The incidence of mild BPD [8 cases (22.2%) vs.16 cases (44.4%), χ2=4.000, P=0.046] and stage Ⅰ-Ⅱ ROP [11 cases (30.6%) vs.22 cases (61.1%), χ2=6.769, P=0.009] in the LISA group was significantly lower than that of the INSURE group.There was no significant difference in the incidence of moderate and severe BPD and stageⅢ ROP and above between groups (all P>0.05). (2)There were no statistical differences in the repeated use of PS, mechanical ventilation rate within 72 h, pneumothorax/pulmonary hemorrhage, grade Ⅲ-Ⅳ periventricula-rintraventricular hemorrhage, stage Ⅱ-Ⅲ neonatal necrotizing enterocolitis, sepsis, abnormal amplitude integrated electroencephalogram, mortality in 36 weeks of corrected gestational age, total oxygen inhalation duration and hospitalization duration between the two groups (all P>0.05). (3)Follow-up within 1 year of corrected age after discharge.There were no significant differences in extrauterine body mass, body length and head circumference development, visual development, hearing development, Neonatal Behavioral Neurological Assessment score at corrected gestational age of 40 weeks, Bayley Scales of Infants Development score at corrected gestational age of 6 months and age of 1 year, pneumonia and re-hospitalization due to respiratory diseases between groups (all P>0.05). Conclusions:PS administration with LISA technology can reduce the incidence of mild BPD and stage Ⅰ-Ⅱ ROP in premature infants with NRDS who had the gestational age of 24-31 + 6 weeks and birth weight<1 500 g, without increasing the risk of other complications.The long-term prognosis of them treated with PS administration with LISA and INSURE is similar.

Humans ; Asthma/drug therapy* ; Biological Therapy

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

This study aims to investigate the effect and mechanism of hydnocarpin(HC) in treating triple negative breast cancer(TNBC). Cell counting kit-8(CCK-8), xCELLigence real-time cellular analysis(RTCA), and colony formation assay were employed to determine the effects of HC on the proliferation of two TNBC cell lines: MDA-MB-231 and MDA-MB-436. The effects of HC on the migration and invasion of TNBC cells were detected by high-content analysis, wound-healing assay, and Transwell assay. The changes in the epithelial-mesenchymal transition(EMT) and the expression of invasion-and migration-associated proteins [E-cadherin, vimentin, Snail, matrix metalloproteinase-2(MMP-2), and MMP-9] were detected by Western blot. Western blot and RT-qPCR were employed to determine the protein and mRNA levels of Yes-associated protein(YAP) and downstream targets(CTGF and Cyr61). TNBC cells were transfected with Flag-YAP for the overexpression of YAP, and the role of YAP as a key target for HC to inhibit TNBC malignant progression was examined by CCK-8 assay, Transwell assay, and wound-healing assay. The pathway of HC-induced YAP degradation was detected by the co-treatment of proteasome inhibitor with HC and ubiquitination assay. The binding of HC to YAP and the E3 ubiquitin ligase Ccr4-not transcription complex subunit 4(CNOT4) was detected by microscale thermophoresis(MST) assay and drug affinity responsive target stability(DARTS) assay. The results showed that HC significantly inhibited the proliferation, colony formation, invasion, and EMT of TNBC cells. HC down-regulated the protein and mRNA levels of CTGF and Cyr61. HC down-regulated the total protein level of YAP, while it had no effect on the mRNA level of YAP. The overexpression of YAP antagonized the inhibitory effects of HC on the proliferation, migration, and invasion of TNBC cells. HC promoted the degradation of YAP through the proteasome pathway and up-regulated the ubiquitination level of YAP. The results of MST and DARTS demonstrated direct binding between HC, YAP, and CNOT4. The above results indicated that HC inhibited the malignant progression of TNBC via CNOT4-mediated degradation and ubiquitination of YAP.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Matrix Metalloproteinase 2/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Ubiquitination ; RNA, Messenger/metabolism* ; Epithelial-Mesenchymal Transition ; Transcription Factors/metabolism*