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.

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 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.

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.

This study evaluated the scientific nature and effectiveness of iterative optimization of prevention and control measures for local outbreaks caused by the BA.2 and BA.5.2 COVID-19 strains in Fujian Province in 2022,to provide a scientif-ic basis for responding to future new or recurrent respiratory infectious diseases.According to the theory of infectious disease dynamics,relevant information regarding the local epidemic situation caused by the BA.2 sub-type Omicron virus strain in March 2022 and BA.5.2 sub-type Omicron virus strain in October 2022 in Fujian Province was collected.The susceptible exposed infectious removed(SEIAR)model of COVID-19 infection with a latent period and asymptomatic infected persons was used to analyze the transmission dynam-ics of two local epidemic situations,and evaluate the preven-tion and control effects.The incubation period of the BA.2 epidemic was 3 days(1～9 days),the intergenerational inter-val was 3 days(1～5 days),and the initial Rt was 3.0(95％CI:2.7～3.3).The incubation period of the BA.5.2 epidemic was 2 days(1～6 days),the intergenerational interval was 1 day(0～2 days),and the initial R,was 1.9(95％CI:1.7～2.1).The fittingresults for the BA.2 and BA.5.2 epidemics were good,and no statistical difference was observed between the predic-ted and actual numbers of cases(x2BA.2=31.53,x2BA.5.2=27.88,P＞0.05).If an emergency response had not been initiated,the BA.2 epidemic would have continued to spread andpeak on April 7th,with an estimated 638 035 cases.The BA.5.2 epidemic would have rapidly spread,reaching a peak on November 14th,with an estimated 685 940 cases.If one incubation period were detected early,the scale of the BA.2 epidemic would have decreased by 25.73％;if two incubation periods were detected early,the scale would have decreased by 79.56％,and if one incubation period had been delayed,the scale would have expanded by 13.72％.If one incubation period had been detected early in the BA.5.2 epidemic,the scale would have decreased by 35.04％;if two incubation periods had been detected early,the scale would have decreased by 92.47％;and if one incubation period had been delayed,the scale would have increased by 19.75％.The guiding ideology,and the prevention and control measures for handling two local epidemics were optimized and iterated.Our study indicated that implementing the"four early"measures ef-fectively decreased the scale of the epidemic,and earlier detection was associated with more significant control effects.This study provides valuable information for the prevention and control of new or recurrent respiratory infectious diseases.

Objective To explore the value of prophylactic anticoagulation in the 28-day prognosis of patients with severe COVID-19.Methods The clinical data of COVID-19 patients admitted to Guangdong Provincial People's Hospital from December 2022 to January 2023 were collected,including age,gender,past medical history,routine blood test,liver and renal function,procalcitonin,coagulation function,Padua prediction score,antiviral therapy,hormonotherapy,immunotherapy and anticoagulation therapy.The patients were divided into an anticoagula-tion group and a non-anticoagulation group.The differences in various indicators were compared between the two groups.Cox regression was performed to assess the independent risk factors for 28-day mortality and the anticoagula-tion efficacy between the subgroups.Results Among 158 patients,128 received anticoagulation;There were significant differences between the two groups in case number of hypertension and critical condition,lymphocyte count,prothrombin time,D-dimer,and case number of immunotherapy.COX logistic regression showed that antico-agulation(HR = 2.25,95%CI:1.01～5.01,P = 0.048)was an independent risk factor for all-cause mortality of COVID-19 patients within 28 days.Subgroup analysis showed that anticoagulation therapy led to an increase in the 28-day mortality as level of procalcitonin of≥0.5 pg/mL(HR = 2.72,95%CI:1.05～7.04)or D-dimer of<2 000 ng/mL(HR = 9.16,95%CI:1.63～51.48).Conclusions Prophylactic anticoagulation did not reduce all-cause mortality of COVID-19 within 28 days.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

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.

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*