To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective:To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED).Methods:Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed.Results:Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases.Conclusions:CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

About 8 dental schools were founded by Chinese dentists during modern times (1909-1949) in China. Only one still worked after the founding of the People's Republic of China, which was one of the three dental schools founded by dentist Situ Bo. There were no systematic researches on Situ Bo's participation in dentistry education. This paper analyzes the founder's experience in dentistry and in the two schools he founded at the beginning, focusing on the background and process of the schools' construction, management, teaching, teachers and students training, etc. The results show that the establishment of the first two dental schools have laid important foundation for the establishment and development of Shanghai Dental College by the reserve of trained professional teachers and accumulated valuable experience in running schools. The systematic review of this history will help us better understand the establishment and development of Shanghai Dental College and the efforts in dentistry education made by dentists growed up in modern China, as well as the early development process of stomatology.

Objective To evaluate the safety of human purified Vero cell rabies vaccine(PVRV)after exposure in China by Meta-analysis.Methods With rabies,vaccine and safety as key words,a systematic search was performed in PubMed,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI),supplemented by manual retrieval.A Meta-analysis was performed to analyze the incidence of adverse events of two immunization regimens Zagreb and Essen using Review Manager 5.4 software after literature screening and data extraction according to the inclusion and exclusion criteria.Results A total of 12 studies were included,of which 7 were prospective studies and 5 were retrospective studies.Most included in the studies showed a low risk of bias.The incidence of adverse events in Zagreb regimen was significantly higher than that in Essen regimen[relative risk(RR)= 1.01,95% CI = 0.90 ～ 1.14;I2= 73.00%,P<0.05],but there was a high degree of heterogeneity.The incidence of fever,pain and induration in Zagreb regimen was significantly higher than that in Essen regimen(RR = 1.14,0.92 and 0.86,95% CI = 0.82 ～ 1.60,0.73 ～ 1.14 and 0.29 ～ 2.51;I2= 73.00%,P<0.05],but there was a high degree of heterogeneity.The incidence of fever,pain and induration in Zagreb regimen was significantly higher than that in Essen regimen(RR = 1.14,0.92 and 0.86,95% CI = 0.82 ～ 1.60,0.73 ～ 1.14 and 0.29 ～ 2.51;I2= 81%,65% and 92%,respectively,P<0.01).Conclusion Two regimens of PVRV vaccination after exposure showed good safety.However,when adopting Zagreb regimen,attention should be paid to the physical conditions of children and the elderly with relatively poor immunity to avoid adverse events.

Objective: To examine the safety and efficacy of the uniportal video-assisted thoracoscopic decortication in treatment of drug-resistant tuberculosis empyema. Methods: From January 2018 to December 2020, 122 cases of tuberculous empyema treated by decortication in Department of Surgery, Wuhan Pulmonary Hospital were retrospectively analyzed, including 100 males and 22 females, aged(M(IQR)) 29.5(28.0) years (range: 13 to 70 years). According to the surgical approach and drug resistance, patients with drug-resistant tuberculosis who underwent uniportal video-assisted thoracoscopic decortication were included in group A (n=22), and those who underwent thoracotomy decortication were included in group B (n=28). Drug-sensitive patients who underwent uniportal video-assisted thoracoscopic decortication were included in group C (n=72). There was no statistical difference in the baseline data of the three groups (P>0.05). The operation, early postoperative recovery, and prognosis-related indicators were compared among three groups by Kruskal-Wallis test and χ² test by Mann-Whitney U test and Bonferroni method between groups A and B, groups A and C. Results: The intraoperative blood loss of group A, group B, and group C was 200(475) ml, 300(200) ml, and 225(300) ml, respectively. There was no significant difference in intraoperative hemorrhage (H=2.74, P=0.254) and treatment outcome (χ²=4.76, P=0.575) among the three groups. Compared with group B, the operation time of group A (302.5(187.5) minutes vs. 200.0(60.0) minutes, U=171.0, P=0.007) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0 (2.2) months, U=146.5, P=0.032) were longer, and the postoperative drainage duration (9.5(7.8) days vs. 13.0(10.0) days, U=410.0, P=0.044), and the postoperative hospitalization time (12.0(7.8) days vs. 14.5(4.8) days, U=462.2, P=0.020) were shorter. There was no significant difference in complications between group A and group B (63.6%(14/22) vs. 71.4%(20/28), χ²=0.34, P=0.558). Compared with group C, the postoperative drainage duration of group A (9.5(7.8) days vs. 7.0(4.0) days, U=543.5, P=0.031), the postoperative hospitalization time (12.0(7.8) days vs. 9.0(4.0) days, U=533.0, P=0.031) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0(2.0) months, U=961.5, P=0.001) were longer. The operation time (302.5(187.5) minutes vs. 242.5(188.8) minutes, U=670.5, P=0.278), and complications (63.6%(14/22) vs. 40.3%(29/72), χ²=3.70, P=0.054) were not different between group A and group C. Conclusions: For drug-resistant tuberculous empyema, the uniportal video-assisted thoracoscopic decortication can achieve the same good therapeutic effect as drug-sensitive tuberculous empyema, and it is as safe as thoracotomy. At the same time, it has the advantage of minimally invasive and can accelerate the early postoperative recovery of patients.
Female ; Male ; Humans ; Empyema, Tuberculous/surgery* ; Retrospective Studies ; Thoracic Surgery, Video-Assisted ; Drainage ; Blood Loss, Surgical ; Tuberculosis, Multidrug-Resistant/surgery*

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Mice ; Animals ; Diabetes Mellitus, Type 2/genetics* ; Streptozocin/pharmacology* ; Diet, High-Fat/adverse effects* ; Proteomics ; Inflammation ; TOR Serine-Threonine Kinases ; Autophagy ; Mammals

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age (P=0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P>0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas (P=0.004),large adenomas (P=0.006),adenomas in distal colon (P=0.015),protruding polyps (P=0.044),and late-stage pathology (P=0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification (P=0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign (P<0.001,P=0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign (P=0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign (P=0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.
Adult ; Humans ; Cyclooxygenase 2 ; Snow ; Colorectal Neoplasms ; Adenoma

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.