OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

To study the clinical effect of non-ampullary duodenal mucosal lesions treated by endoscopic resection. A retrospective analysis was performed on the data of 58 cases of duodenal non-ampullary mucosal lesions treated by endoscopic resection from January 2016 to June 2019 from 3 hospitals. Among 58 cases, 27 lesions (46.6%) were located in the duodenal bulb and 31 (53.4%) in the duodenal descending part (including the ball-drop boundary). Forty-six patients (79.3%) received endoscopic mucosal resection, 7 (12.1%) received endoscopic submucosal dissection and 5 (8.6%) received pre-cut endoscopic mucosal resection. Few postoperative complications were found except for 1 case of intraoperative bleeding, 1 case of delayed bleeding 2 days after surgery, 1 case of lesion residual and 2 cases of postoperative abdominal pain. No perforation occurred. Endoscopic treatment of non-ampullary duodenal mucosal lesions is safe and effective.

Objective:To observe the changes of nutrition impact symptoms (NIS) and fat-free mass and analyze the relationship between them in patients with head and neck cancer (HNC) during radiotherapy.Methods:A convenient sampling method was adopted to select HNC patients who received radiotherapy in the outpatient clinic of department of radiotherapy for head and neck cancer in a cancer hospital in Beijing from March 2017 to January 2020. The nutrition impact symptoms (NIS) were assessed by a nutrition impact symptoms checklist and the fat free mass was assessed by bioelectrical impedance analysis at three time points: before radiotherapy (T1), during radiotherapy (T2) and at the end of radiotherapy (T3). The Generalized Estimating Equations (GEE) was used to analyze the relationship between them.Results:A total of 542 HNC patients were included in the analysis. During radiotherapy, the patients' NIS number and score presented an increasing trend, reaching the highest level and peaked at the end of radiotherapy. The change of fat-free mass showed a decreasing trend and reached the minimum at the end of radiotherapy. Patients with higher NIS scores had more percentage loss of fat-free mass.Conclusions:During radiotherapy, patients with HNC showed an increase in NIS score and lost fat-free mass. Patients with higher NIS score lost more percentage of fat-free mass, which suggested that clinical medical staff should pay attention to NIS management and take comprehensive intervention measures in time to reduce the loss of fat-free mass.

OBJECTIVE: To analyze the phenotype and genetic basis for a pedigree affected with hereditary coagulation factor XI deficiency. METHODS: Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), FXI activity (FXI:C) and the antigen of FXI (FXI:Ag) were determined for the proband and members from his pedigree. Sanger sequencing was used to analyze all exons, exon-intronic boundaries, as well as the 5'- and 3'- untranslated regions of the F11 gene. Suspected variants were verified in her family members and confirmed by reverse sequencing. The impact of the variants on the protein function was predicted by using PolyPhen-2 and SIFT software. The protein structure and amino acid interaction were analyzed by using Swiss-PdbViewer. RESULTS: The APTT, FXI:C and FXI:Ag of the proband and her sister were significantly reduced to 73.0 s, 10.0%, 15.0% and 87.1 s, 2.0% and 11.5%, respectively. APTT of some family members was slightly prolonged, and FXI:C and FXI:Ag also decreased to various extents. DNA sequencing revealed that the proband and her sister have carried compound heterozygous variants of c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) respectively in exons 7 and 9 of the F11 gene. Her father, sister and daughter were heterozygous for the c.738G>A (p.Trp228stop) variant, while her mother and nephew were heterozygous for the c.938G>T (p.Ser295Ile). Both PolyPhen-2 and SIFT predicted that the p.Ser295Ile variant is likely to be deleterious and can affect the protein function. Modeling analysis indicated that the p.Ser295Ile variant may lead to disruption of a hydrogen bond, resulting in alteration of protein structure and instability. CONCLUSION The compound heterozygous c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) variants of the F11 gene probably underlie the decreased FXI level in this pedigree.
Factor XI Deficiency ; genetics ; Female ; Genetic Variation ; Heterozygote ; Humans ; Mutation ; Pedigree

Objective: To investigate the safety and efficacy of transcatheter perforation of pulmonary valve by micro-guidewire and balloon dilation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The retrospective study included 21 neonates (14 males and 7 females) with PA-IVS who underwent transcatheter micro-guidewire pulmonary valve perforation and balloon dilation in Xinhua Hospital from January 2012 to December 2018. All patients underwent the pulmonary valve perforation by micro-guidewire through the Simmons catheter. During the follow-up period at 1, 3, 6, 12 months postoperatively and annually thereafter, the operative efficacy and the development of the right ventricle (RV) were evaluated by echocardiography. Statistical analyses were performed using t test. Results: A total of 21 neonates with PA-IVS were enrolled, and 13 cases were diagnosed prenatally. The median age of surgery was 6 days, the weight was (3.2±0.5) kg. The balloon/valve ratio was 1.19±0.12, and the RV pressure measured by catheter was (121±33) mmHg (1 mmHg=0.133 kPa) . The immediate postoperative RV pressure was (47±13) mmHg. The median follow-up time was 30 months. All the cases enrolled achieved biventricular circulation without death and serious complications. According to the last follow-up data including 16 cases who were followed up for 1 year or longer, the pulmonary artery transvalvular pressure was (29±15) mmHg. The postoperation ratio of right to left ventricular transverse diameter was significantly higher than that before operation (0.86+0.10 vs. 0.73+0.13, t=-2.96, P=0.006). Compared with preoperative data, the postoperation pulmonary valvular diameter Z-score was significantly higher (-1.41±0.89 vs. -2.83±1.06, t=-3.65, P=0.001) and the tricuspid valvular diameter Z-score was significantly higher (-0.52±0.29 vs. -1.34±0.81, t=-3.55, P=0.001). Conclusion Transcatheter perforation of pulmonary valve by micro-guidewire and balloon dilation is a safe and effective initial therapy for neonatal PA-IVS.

Objective:To investigate the willingness of medical students to work in primary health care institutions.Methods:A cross-section survey was conducted to investigate the willingness and the reasons, involving 597 undergraduate medical students and 2088 junior college students.Results:The employment willingness of undergraduate medical students was relatively low (14.9%), while the employment willingness of junior college students was high (56.02%). The top three factors of low employment willingness were: less opportunities for personal development, poor working environments and welfare. Moreover, the most effective method to cultivate medical students was developing a free training project for rural-oriented medical students, and the best method to attract medical students was formulating a more beneficial comprehensive policy.Conclusion:The willingness of clinical medical students to be employed in primary health care institutions is low for the time being. It is suggested to improve their willingness by improving welfare benefits, providing personal development opportunities, and strengthening social security.

Objective:To investigate the indication of pre-cut-endoscopic mucosal resection (pre-cut-EMR) on the treatment of colorectal laterally spreading tumors (LSTs).Methods:A retrospective study was performed on data of colorectal LSTs patients, who underwent pre-cut-EMR in Wuxi Second People’s Hospital and Zhongshan Hospital from January 2014 to June 2019. The relationships between the clinical characteristics of the lesions and the success rate and complications of pre-cut-EMR were analyzed.Results:Data of 132 colorectal LSTs cases were included in the study. Morphology of 29 (22.0%) LSTs were homogeneous granular type, 43 (32.6%) LSTs were mixed non-granular type, 58 (43.9%) LSTs were flat elevated type, and 2 (1.5%) LSTs were pseudo-depressed type. The diameter of lesions was 2.3±1.5 cm (ranged from 2.0 cm to 5.0 cm). Among the 132 LSTs, 36 (27.3%) tumors were located in rectum, 15 (11.4%) in sigmoid colon, 10 (7.6%) in descending colon, 17 (12.9%) in splenic flexure of colon, 21 (15.9%) in transverse colon, 24 (18.2%) in hepatic flexure of colon, 6 (4.5%) in ascending colon, and 3 (2.3%) in cecum. The histopathological diagnoses of the 132 LSTs included low grade intraepithelial neoplasia in 58 cases (43.9%), high grade intraepithelial neoplasia in 69 cases (52.3%), intramucosal carcinoma in 2 cases (1.5%), and canceration in 3 cases (2.3%). Pre-cut-EMR was achieved in all 132 patients, and the operation time was 25.3±13.6 min (ranged 20-65 min). The rate of en bloc resection and complete resection were 95.5% (126/132) and 100.0% (132/132), respectively. Two cases (1.5%) had intraoperative perforation, and were both located in the sigmoid colon with the diameter of 4.0 cm and 4.5 cm, respectively. Twelve cases (9.0%) had immediate bleeding during operation, and 2 cases (1.5%) had delayed bleeding after operation. Patients had been followed up for 6-24 months, the wound healed well after operation, and no local recurrence was found.Conclusion:Pre-cut-EMR is an effective and safe therapy for colorectal LSTs with diameter less than 4.0 cm.